Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

Science.gov (United States)

de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

Determination of hepatic fractional clearance of radioactive gold colloids for a measure of effective hepatic blood flow

International Nuclear Information System (INIS)

Fujii, Masahiro

1979-01-01

For a measure of effective blood flow, a hepatic fractional clearance of 198 Au-colloids was determined, which was obtained from the disappearance rate multiplied by the fraction of injected dose taken up by the liver. The hepatic uptake was determined with a gamma camera. The counts over the liver was corrected for body weight and height. The method was considered sufficiently simple for routine use. 198 Au-colloids were obtained from Dainabot Lab. and CIS. The former gave 64% higher values of disappearance rate than the latter, without any change in the organ distribution. A quality control tests were applied over a six-year period to the disappearance rates. Reproducibility within 95 to confidence limits was found for both groups. In 28 normal control subjects, hepatic fractional clearance of the colloids from Dainabot Lab. was 18.5 +- 3.4%/min. In patients with progressed hepatic disease, both hepatic fractional clearance and final hepatic uptake were decreased, showing that the determination of hepatic uptake is necessary in measuring effective hepatic blood flow by the colloidal clearance method. The influence of splenic uptake is discussed in relation to hepatic blood flow measurement. (author)

Hepatitis b vaccination uptake among a cohort of nigerian surgical ...

African Journals Online (AJOL)

Background and Objectives: Transmission of Hepatitis B virus (HBV) from patients to health care personnel (HCP) can occur following occupational exposures. Vaccination is effective in disease prevention. The study aimed to determine the level of uptake of HBV vaccine among a cohort of Nigerian surgical residents.

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

Science.gov (United States)

Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

2017-06-01

Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) - extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at thyroid

International Nuclear Information System (INIS)

Matsui, Hideaki; Udaka, Fukashi; Oda, Masaya; Tamura, Akiko; Kubori, Tamotsu; Nishinaka, Kazuto; Kameyama, Masakuni

2005-01-01

Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. The objective of this study was to compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p<0.0001) and multiple system atrophy (p=0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p=0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p=0.010). Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid. (author)

F-18 FDG Uptake in an Eosinophilic Liver Abscess Mimicking Hepatic Metastasis on PET/CT Images

International Nuclear Information System (INIS)

Sohn, Myung Hee; Jeong, Hwan Jeong; Lim, Seok Tae; Kim, Dong Wook; Yin, Chang Yeol

2008-01-01

A 61-year-old man had a F-18 FDG PET/CT scan for evaluation of a common bile duct cancer identified on CT. The PET/CT image showed a hypermetabolic mass in the common bile duct, and a focal area of increased F-18 FDG uptake in segment IV of the liver, which corresponded to a hypoattenuated lesion on non-enhanced CT, and was consistent with hepatic metastasis. The patient underwent choledochojejunostomy with hepatic resection, and pathologic findings were compatible with an eosinophilic abscess in the liver. This case demonstrates that F-18 FDG uptake by an eosinophilic abscess can mimic hepatic metastasis in a patient with a malignancy

F-18 FDG Uptake in an Eosinophilic Liver Abscess Mimicking Hepatic Metastasis on PET/CT Images

Energy Technology Data Exchange (ETDEWEB)

Sohn, Myung Hee; Jeong, Hwan Jeong; Lim, Seok Tae; Kim, Dong Wook; Yin, Chang Yeol [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2008-06-15

A 61-year-old man had a F-18 FDG PET/CT scan for evaluation of a common bile duct cancer identified on CT. The PET/CT image showed a hypermetabolic mass in the common bile duct, and a focal area of increased F-18 FDG uptake in segment IV of the liver, which corresponded to a hypoattenuated lesion on non-enhanced CT, and was consistent with hepatic metastasis. The patient underwent choledochojejunostomy with hepatic resection, and pathologic findings were compatible with an eosinophilic abscess in the liver. This case demonstrates that F-18 FDG uptake by an eosinophilic abscess can mimic hepatic metastasis in a patient with a malignancy.

Congenital syphylitic hepatitis: a case report with multiple imaging modalities (syphilitic hepatitis)

Energy Technology Data Exchange (ETDEWEB)

Heyman, S; Rosenberg, H K; Mandell, G A; Golden, D A

1983-11-14

A case of syphilitic hepatitis is described with no evidence of mass effect on the ultrasonic and computerized tomographic study, but with discrete areas of decreased uptake on liver scan suggestive of space-occupying lesion. This is the second instance in the literature of the incongruence of the liver scan and the other imaging modalities in syphilitic hepatitis.

Congenital syphylitic hepatitis: a case report with multiple imaging modalities (syphilitic hepatitis)

International Nuclear Information System (INIS)

Heyman, S.; Rosenberg, H.K.; Mandell, G.A.; Golden, D.A.

1983-01-01

A case of syphilitic hepatitis is described with no evidence of mass effect on the ultrasonic and computerized tomographic study, but discrete areas of decreased uptake on liver scan suggestive of space-occupying lesion. This is the second instance in the literature of the incongruence of the liver scan and the other imaging modalities in syphilitic hepatitis. (orig.)

Decreased uptake after fractionated ablative doses of iodine-131

Energy Technology Data Exchange (ETDEWEB)

Wu, Hurng-Sheng [Show Chwan Memorial Hospital, Department of Surgery, Changhua, Taiwan (Taiwan); Hseu, Huey-Herng [Taichung Veterans General Hospital, Department of Medical Education and Research, Taichung (Taiwan); Lin, Wan-Yu; Wang, Shyh-Jen [Taichung Veterans General Hospital, Department of Nuclear Medicine, Taichung, Taiwan (Taiwan); Liu, Yao-Chi [Department of Surgery, General Surgery, National Defense Medical Center, Taipe (Taiwan)

2005-02-01

In an attempt to obviate the necessity for hospitalisation, the ablative dose of {sup 131}I in the treatment of thyroid cancer is divided into two or three fractions at weekly intervals in some hospitals with no special bed for {sup 131}I treatment. Thyroid stunning has been observed in patients receiving a {sup 131}I dose between 74 and 370 MBq (2-10 mCi). However, the influence of {sup 131}I uptake after administration of a higher dose, such as 1,110-1,850 MBq of {sup 131}I, has never been reported. In this study, we evaluated the degree of reduction in {sup 131}I uptake after patients received 1,480 MBq of {sup 131}I and evaluated the clinical value of fractionated ablative doses of {sup 131}I. Thirty-five patients with functional thyroid cancer received a total of 4,440 MBq (120 mCi) of {sup 131}I which was divided into three fractions administered at weekly intervals. In all patients two {sup 131}I whole-body scans were performed. The first scan was performed directly prior to the second dose of {sup 131}I (7 days after the first administration of {sup 131}I), and the second scan was performed 7 days after the second administration of {sup 131}I and directly prior to the third administration. Regions of interest including the neck and lungs were drawn to calculate the uptake of {sup 131}I in the thyroid remnant and possible cervical lymph node and lung metastases. The mean uptake of {sup 131}I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. The decrease in {sup 131}I uptake was significant in all patients except the two with lung metastases. In the two patients with lung metastases, no definite evidence of decreased uptake was noted; the uptake of {sup 131}I in the lung metastases even increased on the second {sup 131}I image in one of these patients. After administration of 1,480 MBq of {sup 131}I, the decreased uptake was significant in all

Xe-133 accumulation in fatty liver: hepatic uptake and washout correlated with pulmonary and mesenteric retention

International Nuclear Information System (INIS)

Samuels, L.D.

1980-01-01

Xe-133 uptake in patients with fatty livers is described and compared with uptake and retention in lungs, blood and mesenteric fat and with normal hepatic uptake. In the absence of obstructive lung disease or excessive obesity, Xe-133 uptake and retention is a valuable means of screening patients for the presence of fatty liver. Although non-specific for the etiology of fatty liver, the test is an effective and non-invasive method of detection which merits further application. (author)

Risk perception of hepatitis B infection and uptake of hepatitis B vaccine among students of tertiary institution in Jos.

Science.gov (United States)

Chingle, M P; Osagie, I A; Adams, H; Gwomson, D; Emeribe, N; Zoakah, A I

2017-01-01

Hepatitis B virus (HBV) Infection is endemic in Nigeria. Healthcare students are more vulnerable because of direct contact with patients' body fluids and blood. Risk perception of HBV and HB vaccine uptake are also poor. The aim of this study was to assess the level of risk perception of hepatitis B infection, and uptake of the HBV vaccine, between medical and other students of the University of Jos. A comparative cross sectional study was conducted among 1,200 students of the departments of Medicine, Nursing sciences and Public Administration, University of Jos (400 from each arm) using a pretested self-administered questionnaire. A five point Likert scoring system was used to assess risk perception. Data was analyzed using SPSS version 20. A P -value of risk perception was 76.8%. This was also similar for medical and nursing students (40.7% and 40.1% respectively), but lower for public administration students (9.1%), PRisk perception is 5x higher among medical students compared to public administration students (OR = 5.22, 95% CI = 2.19 - 12.93; P risk perception on HBV infection are high among University of Jos students, but uptake of HB vaccine is low. Findings are worst for non-health students.

Diffuse hepatic and splenic 99mTc MPD tracer uptake in case of multiple myeloma

International Nuclear Information System (INIS)

Sood, Ashwani; Seam, Rajeev Kumar; Sethi, Sandeep; Gupta, Manish

2010-01-01

99m Tc-methylene diphosphonate (MDP) bone scintigraphy has long been used for the evaluation of benign as well as malignant skeletal conditions. However, non-osseous tracer uptake on a bone scan is an unusual finding. There is a need to understand the pathophysiological basis of the non-osseous uptake, which may have a clinical relevance or deteriorating effect on the quality of the bone scan. We describe a case of multiple myeloma, where extraosseous uptake in the form of diffuse hepatic and splenic uptake, with almost normal skeletal tracer distribution, has been seen on the bone scan. (author)

Tumor and liver drug uptake following hepatic artery and portal vein infusion

International Nuclear Information System (INIS)

Sigurdson, E.R.; Ridge, J.A.; Kemeny, N.; Daly, J.M.

1987-01-01

Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13 N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3 H-FUdR (1 microCi/kg) and /sup 99m/Tc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3 H and /sup 99m/Tc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery

Decreased cisplatin uptake by resistant L1210 leukemia cells

International Nuclear Information System (INIS)

Hromas, R.A.; North, J.A.; Burns, C.P.

1987-01-01

Cisplatin resistance remains poorly understood compared to other forms of anti-neoplastic drug resistance. In this report radiolabelled cisplatin and rapid separation techniques were used to compare drug uptake by L1210 leukemia cells that are sensitive (K25) or resistant (SCR9) to cisplatin. Uptake of cisplatin by both cell lines was linear without saturation kinetics up to 100 μM. The resistant ZCR9 cells had 36-60% reduced drug uptake as compared to its sensitive parent line, K25. In contrast, there was no difference in the rate of efflux. We conclude that a decreased rate of uptake is one possible mechanism of cellular cisplatin resistance. (Author)

Effect of ethionine on hepatic mitochondrial and microsomal calcium uptake

International Nuclear Information System (INIS)

Agarwal, A.K.; Zinermon, W.D.; Latoni, L.

1988-01-01

Ethionine, an ethyl analog of methionine, produces a variety of physiological and pathological effects in animals. These range from acute effects in the liver, kidney, pancreas, and other organs to liver carcinogenesis. Female rats when injected with ethionine exhibit a rapid decrease in hepatic adenosine triphosphate levels followed by a marked inhibition of RNA and protein synthesis and accumulation of triglycerides. Since calcium transport in mitochondria and microsomes is ATP dependent, it becomes interesting to find out if ethionine administration has any effect on subcellular calcium transport. Calcium has recently gained an increased controversy regarding its role in chemical induced lethal cell damage. Certain groups believe that influx of extracellular calcium across the damaged plasma membrane might actually mediate the irreversible damage to the cell, whereas according to other, entry of calcium into the cell is secondary to the damage. The present study was carried out to investigate the calcium [ 45 Ca] transport in mitochondria and microsomes following ethionine administration. The effect of carbon tetrachloride on calcium uptake in ethionine treated rats was also studied

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

International Nuclear Information System (INIS)

Mackey, W.C.; Connolly, R.J.; Callow, A.D.

1984-01-01

The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency

Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus

NARCIS (Netherlands)

Borra, Ronald; Lautamaki, Riikka; Parkkola, Riitta; Komu, Markku; Sijens, Paul E.; Hallsten, Kirstl; Bergman, Jorgen; Iozzo, Patricia; Nuutila, Pirjo

2008-01-01

The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was

Vaccination uptake and awareness of a free hepatitis B vaccination program among female commercial sex workers.

Science.gov (United States)

Baars, Jessica E; Boon, Brigitte J F; Garretsen, Henk F; van de Mheen, Dike

2009-01-01

We sought to explore the reach of a free hepatitis B vaccination program among female commercial sex workers (CSWs) within a legalized prostitution setting in the Netherlands. We also investigated the reasons for nonparticipation and noncompliance. In this cross-sectional study based on ethnographic mapping and targeted sampling, 259 CSWs were interviewed at their work in 3 regions in the Netherlands. The semistructured interviews contained questions on sociodemographics, sexual risk behavior, sex work, awareness of the opportunity to obtain free hepatitis B vaccination, vaccination uptake, and compliance with the full vaccination schedule. Of our sample, 79% reported awareness of the opportunity to obtain hepatitis B vaccination, and 63% reported to be vaccinated against hepatitis B (received > or =1 vaccination). A personal approach by health professionals or was associated with vaccination uptake, when specific sociodemographic variables, sexual behavior, and sex work related covariates were controlled for in the analysis. Window prostitution and the duration of working in the region were associated with awareness of the opportunity to obtain free hepatitis B vaccination. The results of this study suggest that outreach activities (i.e., a personal approach) within this program are beneficial. Transient CSWs are more difficult to reach within the current vaccination program. These results can be used to increase the success of future health programs among this risk group.

Hepatic macrophage complement receptor clearance function following injury.

Science.gov (United States)

Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

1986-03-01

Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA

DEFF Research Database (Denmark)

Grint, D; Peters, L; Schwarze-Zander, C

2013-01-01

All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV infection and ≥ F2 fibrosis should be considered for HCV therapy. This study aimed to determine the rate of HCV treatment uptake among coinfected patients in Europe....

Hepatic bilirubin uptake in the isolated perfused rat liver is not facilitated by albumin binding

International Nuclear Information System (INIS)

Stollman, Y.R.; Gaertner, U.; Theilmann, L.; Ohmi, N.; Wolkoff, A.W.

1983-01-01

Bilirubin uptake by the liver has kinetic characteristics which suggest carrier-mediation. Bilirubin is readily bound to albumin. A liver cell surface receptor for albumin has been postulated. The present study was designed to examine directly whether albumin facilitates the hepatic uptake of bilirubin and whether uptake of bilirubin depends on binding to albumin. Rat liver was perfused with a protein-free fluorocarbon medium, and single-pass uptake of 1, 10, or 200 nmol of [ 3 H]bilirubin was determined after injection as an equimolar complex with 125 I-albumin, with 125 I-ligandin, or free with only a [ 14 C]sucrose reference. Uptake of 10 nmol of [ 3 H]bilirubin was 67.5 +/- 3.7% of the dose when injected with 125 I-albumin, 67.4 +/- 6.5% when injected with 125 I-ligandin, and 74.9 +/- 2.4% when injected with [ 14 C]sucrose (P greater than 0.1). At 200 nmol, uptake fell to 46.4 +/- 3.1% ( 125 I-albumin) and 63.3 +/- 3.4% [( 14 C]sucrose) of injected [ 3 H]bilirubin (P less than 0.01), which suggests saturation of the uptake mechanism. When influx was quantitated by the model of Goresky, similar results were obtained. When [ 3 H]bilirubin was injected simultaneously with equimolar 125 I-albumin and a [ 14 C]sucrose reference, there was no delay in 125 I-albumin transit as compared with that of [ 14 C]sucrose. This suggested that the off-rate of albumin from a putative hepatocyte receptor would have to be very rapid, which is unusual for high affinity receptor-ligand interaction. There was no evidence for facilitation of bilirubin uptake by binding to albumin or for interaction of albumin with a liver cell surface receptor. These results suggest that the hepatic bilirubin uptake mechanism is one of high affinity which can extract bilirubin from circulating carriers such as albumin, ligandin, or fluorocarbon

Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

Directory of Open Access Journals (Sweden)

Furlanetto T.W.

2001-01-01

Full Text Available Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 ± 0.370 to 2.085 ± 0.364 pmol I-/µg DNA at 1 ng/ml (P<0.02, to 1.970 ± 0.302 pmol I-/µg DNA at 10 ng/ml (P<0.003, and to 2.038 ± 0.389 pmol I-/µg DNA at 100 ng/ml (P<0.02. In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 ± 0.408 to 7.312 ± 0.506 pmol I-/µg DNA (P<0.02. A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance.

Science.gov (United States)

Kurabayashi, Atsushi; Tanaka, Chiharu; Matsumoto, Waka; Naganuma, Seiji; Furihata, Mutsuo; Inoue, Keiji; Kakinuma, Yoshihiko

2018-05-01

Our previous study revealed that cyclic hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Transport mechanisms of hepatic uptake and bile excretion in clinical hepatobiliary scintigraphy with 99mTc-N-pyridoxyl-5-methyltryptophan

International Nuclear Information System (INIS)

Kobayashi, Masato; Nakanishi, Takeo; Nishi, Kodai; Higaki, Yusuke; Okudaira, Hiroyuki; Ono, Masahiro; Tsujiuchi, Takafumi; Mizutani, Asuka; Nishii, Ryuichi; Tamai, Ikumi; Arano, Yasushi; Kawai, Keiichi

2014-01-01

Introduction: In clinical hepatobiliary scintigraphy, 99m Tc-N-pyridoxyl-5-methyltryptophan ( 99m Tc-PMT) is an effective radiotracer among the 99m Tc-pyridoxylaminates. However, the mechanisms of human hepatic uptake and bile excretion transport of 99m Tc-PMT have not been determined. We thus investigated the transport mechanisms of human hepatic uptake and bile excretion in hepatobiliary scintigraphy with 99m Tc-PMT. Methods: Four solute carrier (SLC) transporters involved in hepatic uptake were evaluated using human embryonic kidney (HEK) and HeLa cells with high expression of SLC transporters (organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporters (OAT)2 and organic cation transporters (OCT)1) after 5 min of 99m Tc-PMT incubation. Metabolic analysis of 99m Tc-PMT was performed using pooled human liver S9. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters for bile excretion were examined using hepatic ABC transporter vesicles human expressing multiple drug resistance 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein or bile salt export pump. 99m Tc-PMT was incubated for 1, 3 and 5 min with ATP or adenosine monophosphate and these vesicles. SPECT scans were performed in normal and Eisai hyperbilirubinemic (EHBR) model rats, deficient in Mrp2 transporters, without and with verapamil (rat Mdr1 and human MDR1 inhibitor) after intravenous injection of 99m Tc-PMT. Results: Uptake of 99m Tc-PMT in HEK293/OATP1B1 and HeLa/OATP1B3 was significantly higher than that in HEK293- and HeLa-mock cells. 99m Tc-PMT was not metabolized in the human liver S9. In vesicles with high expression of ABC transporters, uptake of MDR1 or MRP2 was significantly higher at all incubation times. Bile excretion of 99m Tc-PMT was also identified by comparison between normal and EHBR rats with and without verapamil on in-vivo imaging. Conclusions: Human hepatic uptake of 99m Tc-PMT was transferred

Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats

International Nuclear Information System (INIS)

Koo, S.I.; Algilani, K.; Norvell, J.E.; Henderson, D.A.

1986-01-01

Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina.

Science.gov (United States)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Mabuchi, Megumi; Naya, Masanao; Kawai, Yuko; Tamaki, Nagara

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123I-BMIPP single-photon emission computed tomography (SPECT) and 15O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with 123I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93+/-0.25, 0.86+/-0.21, 0.97+/-0.30, and 0.99+/-0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76+/-1.29, 1.84+/-0.74, 1.37+/-0.39, and 1.08+/-0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01+/-1.38, 2.20+/-0.95, 1.44+/-0.22, and 1.10+/-0.26, respectively. As 123I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced 123I-BMIPP uptake implies decreased MFR.

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

International Nuclear Information System (INIS)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Mabuchi, Megumi; Tamaki, Nagara; Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Naya, Masanao; Kawai, Yuko

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123 I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123 I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123 I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15 O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123 I-BMIPP single-photon emission computed tomography (SPECT) and 15 O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123 I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123 I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with 123 I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93±0.25, 0.86±0.21, 0.97±0.30, and 0.99±0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76±1.29, 1.84±0.74, 1.37±0.39, and 1.08±0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01±1.38, 2.20±0.95, 1.44±0.22, and 1.10±0.26, respectively. As 123 I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced 123 I-BMIPP uptake implies decreased MFR. (orig.)

Variable uptake feature of focal nodular hyperplasia in Tc-99m phytate hepatic scintigraphy/single-photon emission computed tomography-A parametric analysis.

Science.gov (United States)

Hsu, Yu-Ling; Chen, Yu-Wen; Lin, Chia-Yang; Lai, Yun-Chang; Chen, Shinn-Cherng; Lin, Zu-Yau

2015-12-01

Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9-7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors. Copyright © 2015. Published by Elsevier Taiwan.

Decreased bone uptake of technetium-99m polyphosphate in thalassemia major

International Nuclear Information System (INIS)

Valdez, V.A.; Jacobstein, J.G.

1980-01-01

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renal enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings

Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice.

Science.gov (United States)

Slijepcevic, Davor; Roscam Abbing, Reinout L P; Katafuchi, Takeshi; Blank, Antje; Donkers, Joanne M; van Hoppe, Stéphanie; de Waart, Dirk R; Tolenaars, Dagmar; van der Meer, Jonathan H M; Wildenberg, Manon; Beuers, Ulrich; Oude Elferink, Ronald P J; Schinkel, Alfred H; van de Graaf, Stan F J

2017-11-01

The Na + -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild-type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1-transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno-associated virus-mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α-hydroxylase Cyp7a1 expression was strongly down-regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte-models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643). �

Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.

Science.gov (United States)

Lee, Hyo Young; Jun, Dae Won; Kim, Hyun Jung; Oh, Hyunwoo; Saeed, Waqar Khalid; Ahn, Hyeongsik; Cheung, Ramsey C; Nguyen, Mindie H

2018-03-20

A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). Ezetimibe decreased NAS without improving hepatic steatosis.

Reduced {sup 123}I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

Energy Technology Data Exchange (ETDEWEB)

Kageyama, Hiroyuki; Morita, Koichi; Katoh, Chietsugu; Mabuchi, Megumi; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Tsukamoto, Takahiro; Noriyasu, Kazuyuki; Naya, Masanao [Hokkaido University, Department of Cardiovascular Medicine, Sapporo (Japan); Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Kawai, Yuko [Hokko Memorial Hospital, Department of Cardiovascular Medicine, Sapporo (Japan)

2006-01-01

Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. {sup 123}I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced {sup 123}I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate {sup 123}I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with {sup 15}O-water positron emission tomography (PET). We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent {sup 123}I-BMIPP single-photon emission computed tomography (SPECT) and {sup 15}O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. {sup 123}I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. {sup 123}I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. The numbers of segments with {sup 123}I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93{+-}0.25, 0.86{+-}0.21, 0.97{+-}0.30, and 0.99{+-}0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76{+-}1.29, 1.84{+-}0.74, 1.37{+-}0.39, and 1.08{+-}0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01{+-}1.38, 2.20{+-}0.95, 1.44{+-}0.22, and 1.10{+-}0.26, respectively. As {sup 123}I-BMIPP uptake declined, hyperemic MBF and MFR decreased. In chronic stable angina without previous infarction, reduced {sup 123}I-BMIPP uptake implies decreased MFR. (orig.)

Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

Science.gov (United States)

Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

2011-01-01

In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

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

A systematic review of Hepatitis C virus treatment uptake among people who inject drugs in the European Region

DEFF Research Database (Denmark)

Lazarus, Jeffrey V; Sperle, Ida; Maticic, Mojca

2014-01-01

in relation to the number of patients who either: (a) tested HCV antibody-positive; (b) tested positive for HCV-RNA; or (c) tested positive for HCV-RNA and met additional treatment criteria. RESULTS: Twenty-five articles from 12 countries were included in the review. Among groups of drug-using study......BACKGROUND: Fifteen million adults in the World Health Organization European Region are estimated to have active hepatitis C infection. Intravenous drug use is a major hepatitis C transmission route in this region, and people who inject drugs (PWID) constitute a high-risk and high......-prevalence population. A systematic review was conducted to assess levels of hepatitis C treatment uptake among PWID in Europe. METHODS: Searches in MEDLINE and EMBASE were carried out for articles in any language published between 1 January 2000 and 31 December 2012. Articles were included in the review...

The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake

Science.gov (United States)

Yang, Bei

2012-01-01

Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication. PMID:22031934

Evaluation of hepatic atrophy after transcatheter arterial embolization

International Nuclear Information System (INIS)

Chung, Hwan Hoon; Lee, Mee Ran; Oh, Min Cheol; Park, Chul Min; Seol, Hae Young; Cha, In Ho

1995-01-01

Hepatic atrophy has been recognized as a complication of hepatic and biliary disease but we have often found it in follow up CT after transcatheter arterial embolization (TACE). The purpose of this study is to evaluate the characteristics of hepatic atrophy after TACE. Of 53 patients who had TACE. We evaluated the relationship between the incidence of hepatic atrophy and the number of TACE, and also evaluated the average number of TACE in patients with hepatic atrophy. Of 20 patients who had received more than average number of TACE for development of hepatic atrophy (2 times with portal vein obstruction, 2.7 times without portal vein obstruction in this study), we evaluated the relationship between the lipiodol uptake pattern of tumor and the incidence of hepatic atrophy. There were 8 cases of hepatic atrophy (3 with portal vein obstruction, 5 without portal vein obstruction), average number for development of hepatic atrophy were 2.5 times. As the number of TACE were increased, the incidence of hepatic atrophy were also increased. Of 20 patients who received more than average number of TACE for development of hepatic atrophy, we noted 6 cases of hepatic atrophy in 11 patients with dense homogenous lipiodol uptake pattern of tumor and noted only 1 case of hepatic atrophy in 9 patient with inhomogenous lipiodol uptake pattern. Hepatic atrophy was one of the CT findings after TACE even without portal vein obstruction. Average number of TACE was 2.5 times and risk factors for development of hepatic atrophy were portal vein obstruction, increased number of TACE, and dense homogenous lipiodol uptake pattern of tumor

Hepatic uptake and biliary excretion of manganese in the little skate, Leucoraja erinacea.

Science.gov (United States)

Madejczyk, Michael S; Boyer, James L; Ballatori, Nazzareno

2009-05-01

The liver is a major organ involved in regulating whole body manganese (Mn) homeostasis; however, the mechanisms of Mn transport across the hepatocyte basolateral and canalicular membranes remain poorly defined. To gain insight into these transport steps, the present study measured hepatic uptake and biliary excretion of Mn in an evolutionarily primitive marine vertebrate, the elasmobranch Leucoraja erinacea, the little skate. Mn was rapidly removed from the recirculating perfusate of isolated perfused skate livers in a dose-dependent fashion; however, only a small fraction was released into bile (skate hepatocytes in culture. Mn uptake was inhibited by a variety of divalent metals, but not by cesium. Analysis of the concentration-dependence of Mn uptake revealed of two components, with apparent K(m) values 1.1+/-0.1 microM and 112+/-29 microM. The K(m) value for the high-affinity component was similar to the measured skate blood Mn concentration, 1.9+/-0.5 microM. Mn uptake was reduced by nearly half when bicarbonate was removed from the culture medium, but was unaffected by a change in pH from 6.5 to 8.5, or by substitution of Na with Li or K. Mn efflux from the hepatocytes was also rapid, and was inhibited when cells were treated with 0.5 mM 2,4-dinitrophenol to deplete ATP levels. These data indicate that skate liver has efficient mechanisms for removing Mn from the sinusoidal circulation, whereas overall biliary excretion is low and appears to be mediated in part by an ATP-sensitive mechanism.

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

International Nuclear Information System (INIS)

Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

2002-01-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ( 18 F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes

Decreased uptake of cadmium by a resistant strain of Staphylococcus aureus

Energy Technology Data Exchange (ETDEWEB)

Chopra, I

1971-01-01

Penicillinase plasmids, and some related extrachromosomal elements in Staphylococcus aureus, can specify resistance to inorganic ions, including Hg/sup 2 +/ and Cd/sup 2 +/. There is some tentative evidence that resistance to Hg/sup 2 +/ ions is due to the impermeability of the cells to the ions and not to a higher concentration of free -SH groups in resistance to cadmium ions is unknown. Experiments are described which show that there is a markedly decreased rate of uptake of Cd/sup 2 +/ ions by resistant cells when compared with strains that lack the cad-r gene. The uptake of Cd/sup 2 +/ ions has been studied in the cadmium resistant Staphylococcus aureus strain 8325 (..cap alpha...i/sup +/p/sup +/.cad-r.mer-r) and in its cadmium-sensitive derivative, strain 8324(N). Strain 8325(N) was obtained from 8325 (..cap alpha...i/sup +/.cad-r.mer-r) by isolating a variant which had spontaneously lost the ..cap alpha.. penicillinase plasmid specifying resistance to Cd/sup 2 +/ ions. Cadmium uptake was estimated by adding /sup 115m/CdCl/sub 2/ (final concentration: 10/sup -4/M) to exponentially growing cultures of the sensitive and resistant strains and following the uptake of radioactivity.

Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Sano, Katsuhiro; Ichikawa, Tomoaki; Morisaka, Hiroyuki [University of Yamanashi, Department of Radiology, Chuo-City, Yamanashi (Japan); Saitama Medical University International Medical Center, Department of Diagnostic Radiology, Hidaka-City, Saitama (Japan); Motosugi, Utaroh; Ichikawa, Shintaro [University of Yamanashi, Department of Radiology, Chuo-City, Yamanashi (Japan); Enomoto, Nobuyuki [University of Yamanashi, First Department of Internal Medicine, Yamanashi (Japan); Matsuda, Masanori; Fujii, Hideki [University of Yamanashi, First Department of Surgery, Yamanashi (Japan)

2017-02-15

To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01). Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination. (orig.)

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.

Diagnostic value of liver scintigraphy in fulminant hepatitis and severe acute hepatitis

International Nuclear Information System (INIS)

Shiomi, Susumu; Ikeoka, Naoko; Minowa, Takami; Kuroki, Tetsuo; Harihara, Shigeyoshi; Yamamoto, Sukeo; Ochi, Hironobu; Monna, Takeyuki

1985-01-01

Liver scintigraphy was performed in 12 cases with fulminant hepatitis, in 8 cases with severe acute hepatitis and in 44 cases with acute hepatitis. Scintiphotoes of severe hepatitis showed reduction of liver size, marked visualization of the bone marrow and the spleen, so this pattern was useful to differentiate from acute hepatitis. Relative size of the liver calculated by A.L.I. (anterior liver index) showed significant reduction in severe hepatitis compared with that of acute hepatitis. Three of five patients with died of severe hepatitis showed high uptake in the lung and ribs, but none of fifteen patients with severe hepatitis who recovered showed the abnormal accumulation in the lung and in the ribs. (author)

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

Energy Technology Data Exchange (ETDEWEB)

Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-04-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

Science.gov (United States)

Oh, Ah-Reum; Bae, Jin-Sik; Lee, Junghoon; Shin, Eunji; Oh, Byung-Chul; Park, Sang-Chul; Cha, Ji-Young

2016-01-01

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110] PMID:26350747

Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice.

Science.gov (United States)

Lerat, Hervé; Imache, Mohamed Rabah; Polyte, Jacqueline; Gaudin, Aurore; Mercey, Marion; Donati, Flora; Baudesson, Camille; Higgs, Martin R; Picard, Alexandre; Magnan, Christophe; Foufelle, Fabienne; Pawlotsky, Jean-Michel

2017-08-04

Virus-related type 2 diabetes is commonly observed in individuals infected with the hepatitis C virus (HCV); however, the underlying molecular mechanisms remain unknown. Our aim was to unravel these mechanisms using FL-N/35 transgenic mice expressing the full HCV ORF. We observed that these mice displayed glucose intolerance and insulin resistance. We also found that Glut-2 membrane expression was reduced in FL-N/35 mice and that hepatocyte glucose uptake was perturbed, partly accounting for the HCV-induced glucose intolerance in these mice. Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNFα/SOCS3. Higher hepatic glucose production was observed in the HCV mice, despite higher fasting insulinemia, concomitant with decreased expression of hepatic gluconeogenic genes. Akt kinase activity was higher in HCV mice than in WT mice, but Akt-dependent phosphorylation of the forkhead transcription factor FoxO1 at serine 256, which triggers its nuclear exclusion, was lower in HCV mouse livers. These findings indicate an uncoupling of the canonical Akt/FoxO1 pathway in HCV protein-expressing hepatocytes. Thus, the expression of HCV proteins in the liver is sufficient to induce insulin resistance by impairing insulin signaling and glucose uptake. In conclusion, we observed a complete set of events leading to a prediabetic state in HCV-transgenic mice, providing a valuable mechanistic explanation for HCV-induced diabetes in humans. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

International Nuclear Information System (INIS)

Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan-Xiang; Lezmi, Stéphane

2015-01-01

Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

Energy Technology Data Exchange (ETDEWEB)

Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Flaws, Jodi A. [Department of Comparative Biosciences, University of Illinois Urbana-Champaign (United States); Helferich, William G. [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign (United States); Lezmi, Stéphane, E-mail: slezmi@illinois.edu [Department of Pathobiology, University of Illinois Urbana-Champaign (United States)

2015-04-15

Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

A model to study intestinal and hepatic metabolism of propranolol in the dog.

Science.gov (United States)

Mills, P C; Siebert, G A; Roberts, M S

2004-02-01

A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery.

Soy compared with milk protein in a Western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats.

Science.gov (United States)

Panasevich, Matthew R; Schuster, Colin M; Phillips, Kathryn E; Meers, Grace M; Chintapalli, Sree V; Wankhade, Umesh D; Shankar, Kartik; Butteiger, Dustie N; Krul, Elaine S; Thyfault, John P; Rector, R Scott

2017-08-01

Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy vs. dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Male OLETF rats were randomized to "Western" diets containing milk protein isolate (MPI), soy protein isolate (SPI) or 50:50 MPI/SPI (MS) (n=9-10/group; 21% kcal protein) for 16 weeks. SPI attenuated (Pcontent, and hepatic 16:1 n-7 and 18:1 n-7 PUFA concentrations) (Pbacterial 16S rRNA analysis revealed SPI-intake elicited increases (P<.05) in Lactobacillus and decreases (P<.05) in Blautia and Lachnospiraceae suggesting decreases in fecal secondary bile acids in SPI rats. SPI and MS exhibited greater (P<.05) hepatic Fxr, Fgfr4, Hnf4a, HmgCoA reductase and synthase mRNA expression compared with MPI. Overall, dietary SPI compared with MPI decreased hepatic steatosis and diacylglycerols, changed microbiota populations and altered bile acid signaling and cholesterol homeostasis in a rodent model of obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

A longitudinal analysis of the effect of nonmedical exemption law and vaccine uptake on vaccine-targeted disease rates.

Science.gov (United States)

Yang, Y Tony; Debold, Vicky

2014-02-01

We assessed how nonmedical exemption (NME) laws and annual uptake of vaccines required for school or daycare entry affect annual incidence rates for 5 vaccine-targeted diseases: pertussis, measles, mumps, Haemophilus influenzae type B, and hepatitis B. We employed longitudinal mixed-effects models to examine 2001-2008 vaccine-targeted disease data obtained from the National Notifiable Disease Surveillance System. Key explanatory variables were state-level vaccine-specific uptake rates from the National Immunization Survey and a state NME law restrictiveness level. NME law restrictiveness and vaccine uptake were not associated with disease incidence rate for hepatitis B, Haemophilus influenzae type B, measles, or mumps. Pertussis incidence rate, however, was negatively associated with NME law restrictiveness (b = -0.20; P = .03) and diphtheria-pertussis-tetanus vaccine uptake (b = -0.01; P = .05). State NME laws and vaccine uptake rates did not appear to influence lower-incidence diseases but may influence reported disease rates for higher-incidence diseases. If all states increased their NME law restrictiveness by 1 level and diphtheria-pertussis-tetanus uptake by 1%, national annual pertussis cases could decrease by 1.14% (171 cases) and 0.04% (5 cases), respectively.

A Descriptive Model of Patient Readiness, Motivators, and Hepatitis C Treatment Uptake among Australian Prisoners

Science.gov (United States)

Yap, Lorraine; Carruthers, Susan; Thompson, Sandra; Cheng, Wendy; Jones, Jocelyn; Simpson, Paul; Richards, Alun; Thein, Hla-Hla; Haber, Paul; Lloyd, Andrew; Butler, Tony

2014-01-01

Background Hepatitis C virus infection (HCV) has a significant global health burden with an estimated 2%–3% of the world's population infected, and more than 350,000 dying annually from HCV-related conditions including liver failure and liver cancer. Prisons potentially offer a relatively stable environment in which to commence treatment as they usually provide good access to health care providers, and are organised around routine and structure. Uptake of treatment of HCV, however, remains low in the community and in prisons. In this study, we explored factors affecting treatment uptake inside prisons and hypothesised that prisoners have unique issues influencing HCV treatment uptake as a consequence of their incarceration which are not experienced in other populations. Method and Findings We undertook a qualitative study exploring prisoners' accounts of why they refused, deferred, delayed or discontinued HCV treatment in prison. Between 2010 and 2013, 116 Australian inmates were interviewed from prisons in New South Wales, Queensland, and Western Australia. Prisoners experienced many factors similar to those which influence treatment uptake of those living with HCV infection in the community. Incarceration, however, provides different circumstances of how these factors are experienced which need to be better understood if the number of prisoners receiving treatment is to be increased. We developed a descriptive model of patient readiness and motivators for HCV treatment inside prisons and discussed how we can improve treatment uptake among prisoners. Conclusion This study identified a broad and unique range of challenges to treatment of HCV in prison. Some of these are likely to be diminished by improving treatment options and improved models of health care delivery. Other barriers relate to inmate understanding of their illness and stigmatisation by other inmates and custodial staff and generally appear less amenable to change although there is potential for

A descriptive model of patient readiness, motivators, and hepatitis C treatment uptake among Australian prisoners.

Directory of Open Access Journals (Sweden)

Lorraine Yap

Full Text Available BACKGROUND: Hepatitis C virus infection (HCV has a significant global health burden with an estimated 2%-3% of the world's population infected, and more than 350,000 dying annually from HCV-related conditions including liver failure and liver cancer. Prisons potentially offer a relatively stable environment in which to commence treatment as they usually provide good access to health care providers, and are organised around routine and structure. Uptake of treatment of HCV, however, remains low in the community and in prisons. In this study, we explored factors affecting treatment uptake inside prisons and hypothesised that prisoners have unique issues influencing HCV treatment uptake as a consequence of their incarceration which are not experienced in other populations. METHOD AND FINDINGS: We undertook a qualitative study exploring prisoners' accounts of why they refused, deferred, delayed or discontinued HCV treatment in prison. Between 2010 and 2013, 116 Australian inmates were interviewed from prisons in New South Wales, Queensland, and Western Australia. Prisoners experienced many factors similar to those which influence treatment uptake of those living with HCV infection in the community. Incarceration, however, provides different circumstances of how these factors are experienced which need to be better understood if the number of prisoners receiving treatment is to be increased. We developed a descriptive model of patient readiness and motivators for HCV treatment inside prisons and discussed how we can improve treatment uptake among prisoners. CONCLUSION: This study identified a broad and unique range of challenges to treatment of HCV in prison. Some of these are likely to be diminished by improving treatment options and improved models of health care delivery. Other barriers relate to inmate understanding of their illness and stigmatisation by other inmates and custodial staff and generally appear less amenable to change although there

Increase in Dye:Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAW Cells.

Science.gov (United States)

Vaidyanathan, Sriram; Kaushik, Milan; Dougherty, Casey; Rattan, Rahul; Goonewardena, Sascha N; Banaszak Holl, Mark M; Monano, Janet; DiMaggio, Stassi

2016-09-12

Neutral generation 3 poly(amidoamine) dendrimers were labeled with Oregon Green 488 (G3-OG n ) to obtain materials with controlled fluorophore:dendrimer ratios (n = 1-2), a mixture containing mostly 3 dyes per dendrimer, a mixture containing primarily 4 or more dyes per dendrimer ( n = 4+), and a stochastic mixture ( n = 4 avg ). The UV absorbance of the dye conjugates increased linearly as n increased and the fluorescence emission decreased linearly as n increased. Cellular uptake was studied in RAW cells and HEK 293A cells as a function of the fluorophore:dendrimer ratio (n). The cellular uptake of G3-OG n ( n = 3, 4+, 4 avg ) into RAW cells was significantly lower than G3-OG n ( n = 1, 2). The uptake of G3-OG n ( n = 3, 4+, 4 avg ) into HEK 293A cells was not significantly different from G3-OG 1 . Thus, the fluorophore:dendrimer ratio was observed to change the extent of uptake in the macrophage uptake mechanism but not in the HEK 293A cell. This difference in endocytosis indicates the presence of a pathway in the macrophage that is sensitive to hydrophobicity of the particle.

Is the renal uptake of 99mTc-DMSA decreased in microalbuminuric diabetic patient?

International Nuclear Information System (INIS)

Kim, Seong Jang; Kim, In Ju; Kim, Yong Ki

1999-01-01

Diabetic nephropathy is the most common cause of end stage renal disease and the incidence is progressively increasing. The aim of this study was to investigate the differences of 99m Tc-DMSA renal uptake among diabetic patients with normoalbuminuria, microalbuminuria and overt proteinuria, and then to determine the clinical usefulness of 99m Tc-DMSA in predicting early diabetic nephropathy. 99m Tc-DMSA scan was performed and a total renal uptake of 99m Tc-DMSA was measured in 145 diabetic patients. Patients were divided into 3 groups according to the amount of 24 hour urinary albumin excretion as Group I (normoalbuminuria, 74 cases ), Group II (microalbuminuria, 39 cases), and Group III (overt proteinuria, 32 cases). The differences of 99m Tc-DMSA renal uptake among the 3 groups and the correlation between the renal uptake of 99m Tc-DMSA and other clinical parameters were analyzed. The total renal uptake of 99m Tc-DMSA of Group II (40.8±11.0%) was significantly lower than that of Group I (54.4±6.3%, p 99m Tc-DMSA total renal uptakes correlated negatively with serum creatinine level (r=0.629, p 99m Tc-DMSA total renal uptake of diabetic patients with microalbuminuria was significantly decreased compared with that of patients of normoalbuminuria. Therefore, 99m Tc-DMSA scan can be used as a diagnostic study for early detection of the diabetic nephropathy

Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice Models

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Qin Yi

2018-03-01

Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD, which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD-induced obesity (DIO mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT, glucose tolerance test (GTT, and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in 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.

Profiling of hepatic gene expression in rats treated with fibric acid analogs

International Nuclear Information System (INIS)

Cornwell, Paul D.; Souza, Angus T. de; Ulrich, Roger G.

2004-01-01

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal β-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPARα activation, although signaling through other receptors (e.g. PPARγ, RXR) or through non-receptor pathways cannot be excluded

Decreased uptake with Sulesomab scintigraphy in a case of extra spinal osteitis;Hypofixation de la scintigraphie au sulesomab dans une osteite extrarachidienne

Energy Technology Data Exchange (ETDEWEB)

Ungureanu, C.M.; Angoue, O.; Blagosklonov, O.; Boulahdour, H. [CHU Jean-Minjoz, Service de medecine nucleaire, 25 - Besancon (France); Pauchot, J. [CHU Jean-Minjoz, Service de chirurgie orthopedique, traumatologique, plastique et readaptation fonctionnelle, 25 - Besancon (France)

2010-04-15

Decreased uptake of ischion osteitis with Sulesomab scintigraphy. We report the case of a 28-year-old man, who underwent surgery for a left gluteal muscle abscess. During the surgery multiple specimens were taken from the abscess and the left ischion. These specimens revealed a coagulase-negative Staphylococcus abscess and a coagulase-negative Staphylococcus ischion osteitis. Bone scintigraphy showed an increased uptake in the ischion, while Sulesomab scintigraphy demonstrated a decreased uptake in the same area. If a decreased uptake of Sulesomab has already been described in bone spine infection, it has not yet been described in extra spinal infectious osteitis, to our knowledge

Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

Energy Technology Data Exchange (ETDEWEB)

Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

2015-02-01

Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose Intolerance in High-Fat Diet-Induced Obese Mice.

Science.gov (United States)

Joung, Hyunchae; Kim, Bobae; Park, Hyunjoon; Lee, Kyuyeon; Kim, Hee-Hoon; Sim, Ho-Cheol; Do, Hyun-Jin; Hyun, Chang-Kee; Do, Myoung-Sool

2017-05-01

Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation. C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for 10 weeks. Although body weights were similar among HFD-fed treatment groups, liver weight was decreased, and glucose tolerance test (GTT) results improved in the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also lower in the FM group, and expressions of genes involved in liver lipid metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER) stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER stress, oxidative stress, and inflammation.

Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C.

Science.gov (United States)

Wu, Jing Yuan J; Shadbolt, Bruce; Teoh, Narci; Blunn, Anne; To, Caroline; Rodriguez-Morales, Ilys; Chitturi, Shivakumar; Kaye, Graham; Rodrigo, Kalyana; Farrell, Geoff

2014-06-01

Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments.

Science.gov (United States)

Watanabe, Takao; Kusuhara, Hiroyuki; Watanabe, Tomoko; Debori, Yasuyuki; Maeda, Kazuya; Kondo, Tsunenori; Nakayama, Hideki; Horita, Shigeru; Ogilvie, Brian W; Parkinson, Andrew; Hu, Zhuohan; Sugiyama, Yuichi

2011-06-01

The present study investigated prediction of the overall renal tubular secretion and hepatic clearances of anionic drugs based on in vitro transport studies. The saturable uptake of eight drugs, most of which were OAT3 substrates (rosuvastatin, pravastatin, pitavastatin, valsartan, olmesartan, trichlormethiazide, p-aminohippurate, and benzylpenicillin) by freshly prepared human kidney slices underestimated the overall intrinsic clearance of the tubular secretion; therefore, a scaling factor of 10 was required for in vitro-in vivo extrapolation. We examined the effect of gemfibrozil and its metabolites, gemfibrozil glucuronide and the carboxylic metabolite, gemfibrozil M3, on pravastatin uptake by human kidney slices. The inhibition study using human kidney slices suggests that OAT3 plays a predominant role in the renal uptake of pravastatin. Comparison of unbound concentrations and K(i) values (1.5, 9.1, and 4.0 μM, for gemfibrozil, gemfibrozil glucuronide, and gemfibrozil M3, respectively) suggests that the mechanism of the interaction is due mainly to inhibition by gemfibrozil and gemfibrozil glucuronide. Furthermore, extrapolation of saturable uptake by cryopreserved human hepatocytes predicts clearance comparable with the observed hepatic clearance although fluvastatin and rosuvastatin required a scaling factor of 11 and 6.9, respectively. This study suggests that in vitro uptake assays using human kidney slices and hepatocytes provide a good prediction of the overall tubular secretion and hepatic clearances of anionic drugs and renal drug-drug interactions. It is also recommended that in vitro-in vivo extrapolation be performed in animals to obtain more reliable prediction.

Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

Science.gov (United States)

Wisén, E; Svennerholm, K; Bown, L S; Houltz, E; Rizell, M; Lundin, S; Ricksten, S-E

2018-03-26

Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evaluation of the Potential Impact of Inhibition of Trichloroethylene Metabolism in the Liver on Extra-Hepatic Toxicity

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The interaction between trichloroethylene (TCE) and chloroform (CHCI3) is less than additive, with co-exposure to TCE and CHCl3 resulting in less hepatic and renal toxicity than observed with CHCl3 alone. Vapor uptake data demonstrate that co-exposure to CHCl3 decreases the rate ...

Rain events decrease boreal peatland net CO2 uptake through reduced light availability.

Science.gov (United States)

Nijp, Jelmer J; Limpens, Juul; Metselaar, Klaas; Peichl, Matthias; Nilsson, Mats B; van der Zee, Sjoerd E A T M; Berendse, Frank

2015-06-01

Boreal peatlands store large amounts of carbon, reflecting their important role in the global carbon cycle. The short-term exchange and the long-term storage of atmospheric carbon dioxide (CO2 ) in these ecosystems are closely associated with the permanently wet surface conditions and are susceptible to drought. Especially, the single most important peat forming plant genus, Sphagnum, depends heavily on surface wetness for its primary production. Changes in rainfall patterns are expected to affect surface wetness, but how this transient rewetting affects net ecosystem exchange of CO2 (NEE) remains unknown. This study explores how the timing and characteristics of rain events during photosynthetic active periods, that is daytime, affect peatland NEE and whether rain event associated changes in environmental conditions modify this response (e.g. water table, radiation, vapour pressure deficit, temperature). We analysed an 11-year time series of half-hourly eddy covariance and meteorological measurements from Degerö Stormyr, a boreal peatland in northern Sweden. Our results show that daytime rain events systematically decreased the sink strength of peatlands for atmospheric CO2 . The decrease was best explained by rain associated reduction in light, rather than by rain characteristics or drought length. An average daytime growing season rain event reduced net ecosystem CO2 uptake by 0.23-0.54 gC m(-2) . On an annual basis, this reduction of net CO2 uptake corresponds to 24% of the annual net CO2 uptake (NEE) of the study site, equivalent to a 4.4% reduction of gross primary production (GPP) during the growing season. We conclude that reduced light availability associated with rain events is more important in explaining the NEE response to rain events than rain characteristics and changes in water availability. This suggests that peatland CO2 uptake is highly sensitive to changes in cloud cover formation and to altered rainfall regimes, a process hitherto largely

Congenital syphilitic hepatitis: a radionuclide study

International Nuclear Information System (INIS)

Gates, G.F.; Stanley, P.; Gwinn, J.L.; Miller, J.H.

1978-01-01

A two-month-old girl with congenital syphilitic hepatitis had bizarre liver scintigraphic features showing diminished hepatic uptake of a radiocolloid with accentuated pulmonary and bone marrow accumulation. These features were reversible following penicillin therapy and to our knowledge are previously undescribed manifestations of this multisystemic disease

Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

Science.gov (United States)

Lai, H; Carino, M A

1992-07-01

Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

Science.gov (United States)

Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

2016-02-01

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Profiling of hepatic gene expression in rats treated with fibric acid analogs

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Cornwell, Paul D.; Souza, Angus T. de; Ulrich, Roger G

2004-05-18

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors whose ligands include fatty acids, eicosanoids and the fibrate class of drugs. In humans, fibrates are used to treat dyslipidemias. In rodents, fibrates cause peroxisome proliferation, a change that might explain the observed hepatomegaly. In this study, rats were treated with multiple dose levels of six fibric acid analogs (including fenofibrate) for up to two weeks. Pathological analysis identified hepatocellular hypertrophy as the only sign of hepatotoxicity, and only one compound at the highest dose caused any significant increase in serum ALT or AST activity. RNA profiling revealed that the expression of 1288 genes was related to dose or length of treatment and correlated with hepatocellular hypertrophy. This gene list included expression changes that were consistent with increased mitochondrial and peroxisomal {beta}-oxidation, increased fatty acid transport, increased hepatic uptake of LDL-cholesterol, decreased hepatic uptake of glucose, decreased gluconeogenesis and decreased glycolysis. These changes are likely linked to many of the clinical benefits of fibrate drugs, including decreased serum triglycerides, decreased serum LDL-cholesterol and increased serum HDL-cholesterol. In light of the fact that all six compounds stimulated similar or identical changes in the expression of this set of 1288 genes, these results indicate that hepatomegaly is due to PPAR{alpha} activation, although signaling through other receptors (e.g. PPAR{gamma}, RXR) or through non-receptor pathways cannot be excluded.

Estimation of 123I-metaiodobenzylguanidine lung uptake in heart and lung diseases. With reference to lung uptake ratio and decrease of lung uptake

International Nuclear Information System (INIS)

Fujii, Tadashige; Tanaka, Masao; Yazaki, Yoshikazu; Kitabayashi, Hiroshi; Koizumi, Tomonori; Sekiguchi, Morie; Gomi, Tsutomu; Yano, Kesato; Itoh, Atsuko.

1997-01-01

123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 64 patients with heart and lung diseases. Distribution of MIBG in the chest was evaluated by planar images, using counts ratios of the heart to the mediastinum (H/M) and the unilateral lung to the mediastinum (Lu/M). Most of patients with heart diseases showed obvious lung uptake of MIBG. The ratios of H/M were 1.75±0.20 in the group without heart failure and 1.55±0.19 in the group with heart failure. The ratios of Lu/M in the right and left lung were 1.56±0.16 and 1.28±0.16 in the group without heart failure. And those were 1.45±0.16 and 1.19±0.15 in the group with heart failure. But 3 patients complicated with chronic pulmonary emphysema and one patient with interstitial pneumonia due to dermatomyositis showed markedly decreased lung uptake. The ratios of Lu/M in the right and left lung of these patients were 1.20, 1.17; 1.17, 1.13; 1.01, 0.97 and 1.27, 0.94, respectively. These results suggest that the lung uptake of MIBG may reflect the state of pulmonary endothelial cell function in clinical situations, considering that it has been demonstrated that MIBG may be useful as a marker of pulmonary endothelial cell function in the isolated rat lung. (author)

Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-β-Glucuronide.

Science.gov (United States)

Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

2015-11-02

Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-β-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 μM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1.

The Cascade of Care for an Australian Community-Based Hepatitis C Treatment Service.

Directory of Open Access Journals (Sweden)

Amanda J Wade

Full Text Available Hepatitis C treatment uptake in Australia is low. To increase access to hepatitis C virus treatment for people who inject drugs, we developed a community-based, nurse-led service that linked a viral hepatitis service in a tertiary hospital to primary care clinics, and resulted in hepatitis C treatment provision in the community.A retrospective cohort study of patients referred to the community hepatitis service was undertaken to determine the cascade of care. Logistic regression analyses were used to identify predictors of hepatitis C treatment uptake.Four hundred and sixty-two patients were referred to the community hepatitis service; 344 attended. Among the 279 attendees with confirmed chronic hepatitis C, 257 (99% reported ever injecting drugs, and 124 (48% injected in the last month. Of 201 (72% patients who had their fibrosis staged, 63 (31% had F3-F4 fibrosis. Fifty-five patients commenced hepatitis C treatment; 26 (47% were current injectors and 25 (45% had F3-F4 fibrosis. Nineteen of the 27 (70% genotype 1 patients and 14 of the 26 (54% genotype 3 patients eligible for assessment achieved a sustained virologic response. Advanced fibrosis was a significant predictor of treatment uptake in adjusted analysis (AOR 2.56, CI 1.30-5.00, p = 0.006.Our community hepatitis service produced relatively high rates of fibrosis assessment, hepatitis C treatment uptake and cure, among people who inject drugs. These findings highlight the potential benefits of providing community-based hepatitis C care to people who inject drugs in Australia-benefits that should be realised as direct-acting antiviral agents become available.

Decreased myocardial 123I-MIBF uptake in Parkinson's disease

International Nuclear Information System (INIS)

Iwasa, K.; Takamori, M.; Nakajima, K.; Taki, J.; Yoshikawa, H.; Tada, A.

1998-01-01

We studied myocardial 123 I-metaiodobenzylguanidine (MIBG) accumulation in 12 patients with Parkinson's disease (PD). MIBG is an analog of norepinephrine (NE) and a tracer for sympathetic neuron integrity and function. MIBG uptake of the myocardium was significantly lower in PD than in controls. The heart to mediastinum ratio (H/M) was calculated by using the average count per pixel for the heart and mediastinum. In PD, H/M was lower than in controls (P<0.0001), while the washout ratio of the heart was higher (P<0.001). A decrease in myocardial accumulation of MIBG was observed in the early stage of PD. This suggests that the measurement of MIBF may help the diagnosis of early PD, and the causative factor underlying in PD may be operating the NE neuron as well as dopamine neuron. (au)

Hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver

International Nuclear Information System (INIS)

Weisiger, R.A.; Mendel, C.M.; Cavalieri, R.R.

1986-01-01

Two general models have been proposed for predicting the effects of metabolism, protein binding, and plasma flow on the removal of drugs by the liver. These models differ in the degree of plasma mixing assumed to exist within each hepatic sinusoid. The venous equilibrium model treats the sinusoid as a single well-stirred compartment, whereas the sinusoidal model effectively breaks up the sinusoid into a large number of sequentially perfused compartments which do not exchange their contents except through plasma flow. As a consequence, the sinusoidal model, but not the venous equilibrium model, predicts that the concentration of highly extracted drugs will decline as the plasma flows through the hepatic lobule. To determine which of these alternative models best describes the hepatic uptake process, we looked for evidence that concentration gradients are formed during the uptake of [ 125 I]thyroxine by the perfused rat liver. Autoradiography of tissue slices after perfusion of the portal vein at physiologic flow rates with protein-free buffer containing [ 125 I]thyroxine demonstrated a rapid exponential fall in grain density with distance from the portal venule, declining by half for each 8% of the mean length of the sinusoid. Reversing the direction of perfusate flow reversed the direction of the autoradiographic gradients, indicating that they primarily reflect differences in the concentration of thyroxine within the hepatic sinusoids rather than differences in the uptake capacity of portal and central hepatocytes. Analysis of the data using models in which each sinusoid was represented by different numbers of sequentially perfused compartments (1-20) indicated that at least eight compartments were necessary to account for the magnitude of the gradients seen

Diagnostic value of liver scintigraphy, computed tomography and ultrasonography of fatal hepatitis

International Nuclear Information System (INIS)

Komori, Hideshi; Hirasa, Masahiro; Ibuki, Yasuyoshi

1983-01-01

The purpose of this study was investigate the diagnostic value of liver scintigraphy, computed tomography (CT) and ultrasonography in acute hepatic failure, subacute hepatitis and acute hepatitis. By scintigraphy low uptake in the liver and high uptake in the spleen and bone marrow were observed in hepatic failure. However, uneven liver edge and heterogenous RI destribution were not corresponded to massive necrosis. In fulminant hepatitis, liver size and other findings were variable in patient by patient. But in subacute hepatitis, the findings were typical. The finding of left lobe swelling was observed in a half of patients with acute hepatic failure based on chronic hepatitis. Localized low density area by the CT was detected in most of the cases of subacute hepatitis, and acute hepatitis with submassive hepatic necrosis. But in fulminant hepatitis, that was rare. In these cases, irregular and strong lesion was also obsurved by ultrasonography. These findings by the CT and ultrasonography were corresponded to massive necrosis histrogically ultrasonography revealed narrowing of hepatic vein in fatal hepatitis. Localized low density area by the CT in subacute hepatitis was shown surrounding hepatic vein. We conclude that development of massine hepatic necrosis concern to secondary hepatic ischemia. (author)

Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

International Nuclear Information System (INIS)

Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

2009-01-01

Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

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.)

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

International Nuclear Information System (INIS)

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.

Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis

DEFF Research Database (Denmark)

Bendtsen, Flemming; Henriksen, Jens Henrik; Becker, Povl Ulrik

1987-01-01

.01), azygos venous oxygen saturation (76 vs. 67%, P less than 0.05), ICG clearance (263 vs. 226 ml/min, P less than 0.01), wedged-to-free hepatic vein pressure (16 vs. 13.5 mm Hg, P less than 0.01), hepatic blood flow (1.18 vs. 0.78 l/min, P less than 0.01), cardiac index (3.42 vs. 2.53 l/min . min 2, P less...... mg propranolol. All patients underwent hepatic vein catheterization and had a primed continuous intravenous infusion of ICG. Azygos vein catheterization was performed in six patients. Splanchnic (hepatic-intestinal) oxygen uptake (median control 68 ml/min vs. beta-blockade 56 ml/min, P less than 0...... than 0.01), and heart rate (72 vs. 56 beats per min, P less than 0.01) decreased significantly after oral beta-blockade. The hepatic extraction ratio of ICG increased significantly (0.32 vs. 0.45, P less than 0.01), whereas estimated 'intrinsic' ICG clearance (289 vs. 300 ml/min, n.s.), arterial blood...

Tl-201 per rectum scintigraphy in chronic liver disease: assessment of Tl-201 uptake indices

International Nuclear Information System (INIS)

Moon, Won Jin; Choi, Yun Young; Cho, Suk Shin; Lee, Min Ho

1999-01-01

Heart to liver ratio on Tl-201 per rectal scintigraphy (shunt index) is known to be useful in the assessment of portal systemic shunt. We assessed Tl-201 uptake pattern and early liver/heart uptake rate of Tl-201 and correlated with shunt index in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Fifty eight patients with biopsy-proven chronic liver disease (35 with CAH, 23 with LC) underwent Tl-201 per rectum scintigraphy after instillation of 18.5 MBq of Tl-201 into the upper rectum. We evaluated hepatic uptake (type 1: homogeneous, 2: inhomogeneous segmental, 3: inhomogeneous nonsegmental) and extrahepatic uptake of spleen, heart and kidney (grade 0: no uptake, 1: less than liver, 2: equal to liver, 3: greater than liver). We measured the early liver/heart uptake rate (the slope of the liver to heart uptake ratio for 10 mim) and shunt index (heart to liver uptake ratio). Tl-201 uptake pattern and early liver/heart uptake rate of Tl-201 was correlated with the pathologic diagnosis and shunt index. Hepatic uptake patterns of type 1 and 2 were dominant in CAH (CAH: 27/35, LC: 8/23), and type 3 in LC (CAH: 8/35, LC: 15/23)(p<0.005). The grades of extrahepatic uptake were higher in LC than in CAH (spleen: p<0.001, other soft tissue: p<0.005). The early liver/heart uptake rate of CAH (0.110±0.111) was significantly higher than that of LC (0.014±0.090)(p<0.001). The sensitivity and specificity of the early liver/heart uptake rate were 77.7% and 67.7% in differentiating LC from CAH. There was negative correlation between early liver/heart uptake rate and shunt index (r=-0.3347, p<0.01). Hepatic and extrahepatic uptake pattern and early liver/heart uptake rate on Tl-201 per rectum scintigraphy are useful in the assessment of portal systemic shunt in patients with chronic liver disease

Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

Science.gov (United States)

Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

2011-04-01

We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study

DEFF Research Database (Denmark)

Lindi, Virpi; Schwab, Ursula; Louheranta, Anne

2007-01-01

BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study...

Studies on hemodynamics in liver diseases by the use of colloidal gold198 uptakes by liver and spleen

International Nuclear Information System (INIS)

Matsunaga, Atsushi

1983-01-01

In this study, hepatic blood flow was observed using colloidal gold 198 uptakes by the liver and spleen in the pathogenic conditions in which the uptake was increased in the area of extra hepatic reticuloendothelial systems (especially in splenic RES). The change in the uptake ability of the liver and the contribution to it of intra and extra hepatic shunts were examined. In addition, study was made on the mechanism of how splenic visualization occurred in the colloidal gold 198 scintigram in liver diseases. Out of 84 subjects, 35, 11, 24, and 8 had hepatic cirrhosis and precirrhosis and chronic and acute hepatitis, respectively, and 6 were normal. The results obtained in this study were as follows: (1) The mean value of splenic clearance (splenic blood flow component) in hepatic cirrhosis was 88+-67.5 ml/min. This accounts for approximately 14.6+-11.9 % of the total RES clearance (Classic Effective Hepatic Blood Flow). (2) In hepatic cirrhosis, Classic Hepatic Blood Flow which had been measured up to date was considered to be overestimation by about 19.9+-20.4 % over the mean value of hepatic clearance (hepatic blood flow component) obtained in this study, (3) The hepatic clearance was better indicator of liver disease than the total RES clearance, (4) The ratio between hepatic clearance and cardiac output was considered to be a useful index in assessing the amount of intra and extra hepatic shunts, which had an inverse relationship to the ability of colloid uptake by the liver. (5) Splenic visualization in hepatic cirrhosis was shown to have resulted from the increase in splenic extraction of the colloid, followed by the increase in total splenic blood flow. (author)

Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.

Science.gov (United States)

Farley, Sherry M; Leonard, Scott W; Labut, Edwin M; Raines, Hannah F; Card, David J; Harrington, Dominic J; Mustacich, Debbie J; Traber, Maret G

2012-06-01

The mechanism for increased bleeding and decreased vitamin K status accompanying vitamin E supplementation is unknown. We hypothesized that elevated hepatic α-tocopherol (α-T) concentrations may stimulate vitamin K metabolism and excretion. Furthermore, α-T may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4). In order to investigate these hypotheses, rats were fed phylloquinone (PK) or menadione (MN) containing diets (2 μmol/kg) for 2.5 weeks. From day 10, rats were given daily subcutaneous injections of either α-T (100 mg/kg) or vehicle and were sacrificed 24 h after the seventh injection. Irrespective of diet, α-T injections decreased MK-4 concentrations in brain, lung, kidney, and heart; and PK in lung. These decreases were not accompanied by increased excretion of urinary 5C- or 7C-aglycone vitamin K metabolites, however, the urinary α-T metabolite (α-CEHC) increased ≥ 100-fold. Moreover, α-T increases were accompanied by downregulation of hepatic cytochrome P450 expression and modified expression of tissue ATP-binding cassette transporters. Thus, in rats, high tissue α-T depleted tissue MK-4 without significantly increasing urinary vitamin K metabolite excretion. Changes in tissue MK-4 and PK levels may be a result of altered regulation of transporters. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

{sup 18}F-FDG uptake at the surgical margin after hepatic resection: Patterns of uptake and differential diagnosis

Energy Technology Data Exchange (ETDEWEB)

Peungjesada, Silanath [University New Mexico, Department of Radiology, Albuquerque, NM (United States); Aloia, Thomas A. [University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Unit 444, Houston, TX (United States); Fox, Patricia [University of Texas MD Anderson Cancer Center, Department of Biostatistics, Unit 1411, Houston, TX (United States); Chasen, Beth [University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Unit 1483, Houston, TX (United States); Shin, Sooyoung; Loyer, Evelyne M. [University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Unit 1473, Houston, TX (United States); Baiomy, Ali [Cairo University, National Cancer Center, Cairo (Egypt)

2015-08-15

To evaluate the patterns of {sup 18}F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100 % sensitivity, 87 % specificity, 37 % false positive rate. As expected, SUV{sub max} was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. (orig.)

Hepatic Scintigraphic Findings of Budd-Chiari Syndrome due to Inferior Vena Caval Obstruction

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Hoon; Chung, Soo Kyo; Byun, Jae Young; Lee, Sung Yong; Shinn, Kyung Sub; Kim, Choon Yul; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

1988-03-15

Budd-Chiari syndrome (BCS) is a rare clinical entity characterized by post-sinusoidal portal hypertension caused by the obstruction to the hepatic vein outflow. The diagnosis is suggested by hepatic scintigraphy and is usually confirmed by hepatic venography, inferior vena cavography and biopsy. The scintigraphic finding of BCS caused by the obstruction of main hepatic vein has been reported to consist typically of hypertrophy of the caudate lobe with increased radionuclide accumulation. Such a typical finding has been accounted for by the fact that the venous outflow from the caudate lobe is preserved when the main hepatic vein is obstructed. But usually, the hepatic venous outflow from the caudate lobe is also obstructed in BCS due to inferior vena caval obstruction. So hepatic scintigraphic findings of BCS due to inferior vena caval obstruction show different findings as compared with the BCS due to hepatic vein obstruction. We evaluate the hepatic scintigrams of the 13 cases of BCS due to inferior vena caval obstruction and review the literatures. The results are as follows: 1) We cannot observe the caudate lobe hypertrophy with increased uptake, which is known as a classic finding in BCS due to hepatic vein obstruction. 2) The most prominent hepatic scintigraphic findings of BCS are nonhomogenous uptake in the liver with extrahepatic uptake in the all cases. 3) We can see cold areas at the superior aspect of right hepatic lobe in 7 cases (54%). This is a useful finding suggesting BCS due to inferior vena caval obstruction.

Hepatic Scintigraphic Findings of Budd-Chiari Syndrome due to Inferior Vena Caval Obstruction

International Nuclear Information System (INIS)

Kim, Sung Hoon; Chung, Soo Kyo; Byun, Jae Young; Lee, Sung Yong; Shinn, Kyung Sub; Kim, Choon Yul; Bahk, Yong Whee

1988-01-01

Budd-Chiari syndrome (BCS) is a rare clinical entity characterized by post-sinusoidal portal hypertension caused by the obstruction to the hepatic vein outflow. The diagnosis is suggested by hepatic scintigraphy and is usually confirmed by hepatic venography, inferior vena cavography and biopsy. The scintigraphic finding of BCS caused by the obstruction of main hepatic vein has been reported to consist typically of hypertrophy of the caudate lobe with increased radionuclide accumulation. Such a typical finding has been accounted for by the fact that the venous outflow from the caudate lobe is preserved when the main hepatic vein is obstructed. But usually, the hepatic venous outflow from the caudate lobe is also obstructed in BCS due to inferior vena caval obstruction. So hepatic scintigraphic findings of BCS due to inferior vena caval obstruction show different findings as compared with the BCS due to hepatic vein obstruction. We evaluate the hepatic scintigrams of the 13 cases of BCS due to inferior vena caval obstruction and review the literatures. The results are as follows: 1) We cannot observe the caudate lobe hypertrophy with increased uptake, which is known as a classic finding in BCS due to hepatic vein obstruction. 2) The most prominent hepatic scintigraphic findings of BCS are nonhomogenous uptake in the liver with extrahepatic uptake in the all cases. 3) We can see cold areas at the superior aspect of right hepatic lobe in 7 cases (54%). This is a useful finding suggesting BCS due to inferior vena caval obstruction.

PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

International Nuclear Information System (INIS)

Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Jr, Albert J. Fornace; Peters, Jeffrey M.

2013-01-01

Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering K m , consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity

Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake

International Nuclear Information System (INIS)

Cotting, J.; Zysset, T.; Reichen, J.

1989-01-01

To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after [14C]glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction

Distribution of hepatitis B virus infection in Namibia

African Journals Online (AJOL)

request a laboratory test for hepatitis B for people presenting with jaundice ... surveillance reporting systems for viral hepatitis and uptake of screening for pregnant women in all regions, and ... and clinical information on the patients was sometimes either ..... and management of HBV-positive women and their newborns may.

Blood lipids analysis in patients with hepatitis and hepatic fibrosis

International Nuclear Information System (INIS)

Si Jianhong

2007-01-01

Objective: To investigate the correlationship between blood hepatic fibrosis markers and blood lipids levels. Methods: Serum hepatic fibrosis markers (HA, PC III, IV-C, LN) levels were determined with RIA and serum lipids (TG, TCh HDL; LDL, apoA1, apoB) were measured with biochemical methods in 98 patients with hepatitis in various stages and 50 controls. Liver biopsy was done in all the hepatitis patients. Results: Hepatic fibrosis was classified into 5 grades (S0-S4) according to the pathology shown in the biopsy specimen. The serum lipid levels decreased along with the increase of severity of fibrosis from S0 to S4. Levels in S4 patients were significantly lower than those in controls (P 0.05). Conclusion: The serum hepatic fibrosis markers levels increased and lipids levels decreased along with the progress of hepatitis from acute to cirrhosis. (authors)

Evaluation of hepatic blood flow using 99mTc-GSA in rats with hepatic blood flow manipulation

International Nuclear Information System (INIS)

Hiraguchi, Etsuo

1995-01-01

Blood clearance and hepatic uptake parameters of 99m Tc-DTPA-galactosyl human serum albumin ( 99m Tc-GSA) were evaluated in two groups of rats, normal liver group and CCl 4 induced chronic liver injury group. In each group, four subgroups were classified as follows: simple laparotomy (LAP), hepatic artery ligation (HAL), portal vein ligation (PVL) and both hepatic artery and portal vein ligation (HAL+PVL). 99m Tc-GSA was intravenously injected (50 μg/100 g B.W.) to rats. Heart and liver were targetted as region of interest and time activity curves (TACs) were obtained. The blood clearance parameters (HH4 and Kd) and the hepatic uptake parameters (LHL4 and Ku) were calculated from these TACs. In normal liver group, the mean HH4 of LAP was significantly different from those of PVL and HAL+PVL. Similarly, the other three parameters (LHL4, Kd and Ku) of LAP were significantly different from those of PVL and HAL+PVL. CCl 4 induced chronic liver injury group showed significant difference on all four parameters in four subgroups. Hepatic tissue blood flow rates (HTBFR) calculated by Laser Doppler flowmeter correlated well with 99m Tc-GSA parameters in both groups. These results suggest that 99m Tc-GSA is useful to estimate hepatic blood flow not only in rats with normal liver, but also in rats with CCl 4 induced chronic liver injury. (author)

Superior Glycemic Control with a Glucose-Responsive Insulin Analog: Hepatic and Nonhepatic Impacts.

Science.gov (United States)

Moore, Mary Courtney; Kelley, David E; Camacho, Raul C; Zafian, Peter; Ye, Tian; Lin, Songnian; Kaarsholm, Niels C; Nargund, Ravi; Kelly, Terri M; Van Heek, Margaret; Previs, Stephen F; Moyes, Christopher; Smith, Marta S; Farmer, Ben; Williams, Phil; Cherrington, Alan D

2018-03-14

We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3- 3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2). Whole body insulin clearance (WBIC) and insulin concentrations were not different in P1 vs P2 with HI, but WBIC was 23% higher and arterial insulin 16% lower in P1 vs P2 with GRI. Net hepatic glucose output was similar between treatments in P1. In P2, both treatments induced net hepatic glucose uptake (2.1±0.5 [HI] vs 3.3±0.4 [GRI] mg/kg/min). Nonhepatic glucose uptake (nonHGU, mg/kg/min) in P1 and P2, respectively, differed between treatments (2.6±0.3 and 7.4±0.6 with HI; 2.0±0.2 and 8.1±0.8 with GRI). Thus, glycemia impacted GRI but not HI clearance, with resultant differential effects on HGU and nonHGU. GRI holds promise for decreasing hypoglycemia risk while enhancing glucose uptake under hyperglycemic conditions. © 2018 by the American Diabetes Association.

Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

Science.gov (United States)

Kim, Seong Min; Lee, Bonggi; An, Hye Jin; Kim, Dae Hyun; Park, Kyung Chul; Noh, Sang-Gyun; Chung, Ki Wung; Lee, Eun Kyeong; Kim, Kyung Mok; Kim, Do Hyun; Kim, Su Jeong; Chun, Pusoon; Lee, Ho Jeong; Moon, Hyung Ryong; Chung, Hae Young

2017-07-11

Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice.

Science.gov (United States)

Yan, Caifeng; Chen, Jinfeng; Li, Min; Xuan, Wenying; Su, Dongming; You, Hui; Huang, Yujie; Chen, Nuoqi; Liang, Xiubin

2016-07-01

MicroRNA-9 (miR-9) is involved in the regulation of pancreatic beta cell function. However, its role in gluconeogenesis is still unclear. Our objective was to investigate the role of miR-9 in hepatic glucose production (HGP). MiR-9 expression was measured in livers of high-fat diet (HFD) mice and ob/ob mice. The methylation status of the miR-9-3 promoter regions in hepatocytes was determined by the methylation-specific PCR procedure. The binding activity of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b on the miR-9-3 promoter was detected by chromatin immunoprecipitation (ChIP) and quantitative real-time PCR assays. HGP was evaluated in vitro and in vivo. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were also performed. Reduced miR-9 expression and hypermethylation of the miR-9-3 promoter were observed in the livers of obese mice. Further study showed that the binding of DNMT1, but not of DNMT3a and DNMT3b, to the miR-9-3 promoter was increased in hepatocytes from ob/ob mice. Knockdown of DNMT1 alleviated the decrease in hepatic miR-9 expression in vivo and in vitro. Overexpression of hepatic miR-9 improved insulin sensitivity in obese mice and inhibited HGP. In addition, deletion of hepatic miR-9 led to an increase in random and fasting blood glucose levels in lean mice. Importantly, silenced forkhead box O1 (FOXO1) expression reversed the gluconeogenesis and glucose production in hepatocytes induced by miR-9 deletion. Our observations suggest that the decrease in miR-9 expression contributes to an inappropriately activated gluconeogenesis in obese mice.

Interpretation of Scintigraphic Changes during Chronic Hepatitis and Cirrhosis of the Liver

Energy Technology Data Exchange (ETDEWEB)

Gheorghescu, B.; Jovin, G.; Pavel, D.; Hoanca, O.; Marculescu, Lidia; Suseanu, I.; Sparchez, T. [Centre of Gastroenterology, Bucharest (Romania)

1969-05-15

Photoscintigrams in black and white and in colour were made of the liver and the hepatic clearance was determined by colloidal {sup 198}Au (dimensions 25 - 30 {mu}m) in 82 patients suffering from chronic hepatitis or cirrhosis confirmed by clinical, humeral and histological criteria. The most characteristic changes in the liver scintigram, found particularly in the cirrhosis patients, were: atrophy of the right lobe (partial or total), sometimes pseudo tumoral in appearance; pale or in- homogeneous left lobe; presence of two centres of maximum radiocolloid uptake (left lobe and right lobe); and extrahepatic fixation (spleen, bone marrow). The colour recording system provided better information than the monochromatic system in the diagnosis of cirrhosis. Hepatic clearance showed a decrease, especially in cases of cirrhosis characterized by extrahepatic uptake of the radiocolloid. In the opinion of the authors, the height of the radioactivity curve registered in the temporal region is an indication, during the stabilization phase, of extrahepatic fixation of the colloidal gold. Its height (h{sub 2}) is greater in those cases where the scintigram indicated higher uptake in the spleen and bone marrow. The T 1/2 study of {sup 51}Cr-labelled erythrocytes and their sequestration in the spleen was made in 30 patients exhibiting increased extrahepatic uptake of colloidal gold. The sequestration of labelled erythrocytes was observed in patients showing large-scale splenic uptake of the radiocolloid. Some of the patients whose photoscintigrams previously showed atrophy of the lower region of the right lobe of the liver and obvious presence of the spleen received injections of colloidal gold in the spleen. After intrasplenic injection, the authors obtained the same scintigraphic image in cirrhosis patients, with persistence of the colloidal gold in the spleen, whereas the image of the spleen remained normal in normal subjects. This proves the existence of a lamellar

Clinical Significance of the '99mTc-HIDA Cholescintigraphy in the Neonatal Jaundice

International Nuclear Information System (INIS)

Park, Nan Jae; Kwon, In Soon; Kwon, Jung Sik; Kim, Myung Duk; Lee, Myung Chul; Cho, Bo Yeon; Koh, Chang Soon

1983-01-01

Twenty-nine patients with neonatal jaundice were evaluated with 99m Tc-HIDA cholescintigraphy to elucidate its clinical applicability. Scintigraphic results were interpreted by the degree of early hepatic uptake and the presence or absence of radioactivity in the G-I tract. The results are as follows; 1) In 18 patients with neonatal hepatitis; 8 of 11 patients with decreased hepatic uptake and all 5 patients with good hepatic uptake showed G-I radioactivity. But, the 2 remainders with poor hepatic extraction were not available for evaluation of neonatal jaundice due to patients poor hepatic function. 2) In 9 patients, confirmed as biliary obstruction; all showed no G-I radioactivity but 3 of the 9 showed poor hepatic extraction on scan and they were not available for evaluation. 3) All the 2 patients with postoperative cholangitis showed G-I radioactivity on 99m Tc-HIDA scan. 4) Relationship between histopathologic findings and 99m Tc-HIDA scan; Among 5 patients with biliary cirrhosis 3 showed poor hepatic extraction, the remainders showed decreased and good hepatic uptake respectively. But, the 2 portal fibrosis without cirrhosis and 4 cholestasis showed decreased(4) or good hepatic uptake(2).

Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues

International Nuclear Information System (INIS)

Firth, R.G.; Bell, P.M.; Marsh, H.M.; Hansen, I.; Rizza, R.A.

1986-01-01

Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2- 3 H] or [3- 3 H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM

Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

Science.gov (United States)

Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

2014-01-01

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

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Ryan J Mailloux

Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

Uptake and metabolism of polymerized albumin by rat liver. Role of the scavenger receptor

International Nuclear Information System (INIS)

Wright, T.L.; Roll, F.J.; Jones, A.L.; Weisiger, R.A.

1988-01-01

Hepatitis B virus binds avidly to albumin polymers, which in turn may mediate viral attachment to liver cells. This hypothesis is critically dependent on prior results obtained using glutaraldehyde-polymerized human serum albumin as a model for naturally occurring albumin species. We used the perfused rat liver to characterize the uptake, cellular distribution, and metabolism of glutaraldehyde-polymerized human albumin. 125 I-glutaraldehyde-polymerized human albumin was efficiently removed from the perfusate by the liver (29% extraction). However, few autoradiographic grains were located over hepatic parenchymal cells (6%). Instead, most glutaraldehyde-polymerized human albumin appeared to be removed by endothelial (59%) or Kupffer (31%) cells. Hepatic uptake was strongly inhibited by formaldehyde-treated monomeric albumin, a known ligand of the endothelial scavenger receptor for chemically modified proteins. After uptake, most glutaraldehyde-polymerized human albumin was rapidly degraded and released into the perfusate (74% within 60 min). This process was blocked by chloroquine and leupeptin, suggesting that it involves lysosomal acid hydrolases. We conclude that glutaraldehyde-polymerized albumin is efficiently cleared and degraded by the endothelial scavenger pathway. Glutaraldehyde-polymerized albumin therefore appears to be a poor model for predicting the hepatic handling of naturally occurring albumin species bound to hepatitis B virions. Even if viral particles were to follow this pathway, few would enter parenchymal hepatocytes

Identification of a single sinusoidal bile salt uptake system in skate liver

International Nuclear Information System (INIS)

Fricker, G.; Hugentobler, G.; Meier, P.J.; Kurz, G.; Boyer, J.L.

1987-01-01

To identify the sinusoidal bile acid uptake system(s) of skate liver, photoaffinity labeling and kinetic transport studies were performed in isolated plasma membranes as well as intact hepatocytes. In both preparations photoaffinity labeling with the photolabile bile salt derivative revealed the presence of a predominant bile salt binding polypeptide with an apparent molecular weight of 54,000. The [ 3 H]-labeling of this polypeptide was inhibited by taurocholate and cholate in a concentration-dependent manner and was virtually abolished by 1 mM of the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Kinetic studies of hepatic uptake with taurocholate, cholate, and the photoreactive bile salt derivative indicated the involvement of a single transport system, and all three substrates mutually competed with the uptake of each other. Finally, irreversible inhibition of the bile salt uptake system of photoaffinity labeling of hepatocytes with high concentrations of photolabile derivative reduced the V max but the K m of taurocholate uptake. These findings strongly indicate that a single polypeptide with an apparent molecular weight of 54,000 is involved in sinusoidal bile salt uptake into skate hepatocytes. These findings contrast with similar studies in rat liver that implicate both a 54,000- and 48,000-K polypeptide in bile salt uptake and are consistent with a single Na + -independent transport mechanism for hepatic bile salt uptake in this primitive vertebrate

Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors

International Nuclear Information System (INIS)

Hashimoto, Takashi; Yoneda, Masashi; Shimada, Tadahito; Kurosawa, Mieko; Terano, Akira

2004-01-01

Smoking has been demonstrated to aggravate liver injury. Nicotine, a major pharmacological component of tobacco smoke, affects a multitude of functions. Smoking and nicotine induce synthesis of endothelin (ET)-1. The effect of intraportal infusion of nicotine on hepatic circulation and an involvement of ET-1 and ET receptor in the action of nicotine were investigated in rats. Nicotine (0-100 μg/kg/h) was infused into the portal vein of urethane-anesthetized rats, and changes of hepatic blood flow were evaluated. Intraportal infusion of nicotine dose-dependently decreased hepatic blood flow and increased portal pressure without any alteration of heart rate or arterial blood pressure. This action of intraportal nicotine was completely abolished by pretreatment of ET-1 antibody. Either BQ485 (ET A receptor antagonist) or BQ788 (ET B receptor antagonist) partially reversed the effect of nicotine, and combination of BQ788 and BQ485 completely abolished it. These findings suggest that nicotine inhibits hepatic circulation through ET-1, and ET A and ET B receptor

Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.

Science.gov (United States)

Smits, Loek P; Coolen, Bram F; Panno, Maria D; Runge, Jurgen H; Nijhof, Wouter H; Verheij, Joanne; Nieuwdorp, Max; Stoker, Jaap; Beuers, Ulrich H; Nederveen, Aart J; Stroes, Erik S

2016-03-01

To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P steatosis was 0.87 (95% confidence interval: 0.72, 1.00). This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.

Decreased uptake of 3H-serotonin and endogenous content of serotonin in blood platelets in hypertensive patients

International Nuclear Information System (INIS)

Kamal, L.A.; Le Quan-Bui, K.H.; Meyer, P.

1984-01-01

The uptake and content of serotonin in blood platelets were studied in patients with essential hypertension and in five families in which at least one member was hypertensive. Blood was obtained from male and female normotensive volunteers and hypertensive patients who were free of medication. Lineweaver-Burk plots of 3H-serotonin uptake from both control subjects and hypertensive patients were linear, which suggested simple Michaelis-Menten uptake kinetics. The maximal uptake velocity (Vmax) in hypertensive patients was significantly lower than in control subjects (control . 41.7 +/- 3.3 pmol/min/10(8) platelets, n . 17; hypertensive . 26.6 +/- 3.0 pmol/min/10(8) platelets, n . 16; p less than 0.005). The affinity constant (Km) was slightly but significantly lower in hypertensive patients (control . 0.70 +/- 0.08 microM; hypertensive . 0.46 +/- 0.08 microM; p less than 0.05). The serotonin content in blood platelets determined by high pressure liquid chromatography with electrochemical detection was significantly lower in hypertensive patients (control . 165.0 +/- 12.9 nmol/10(11) platelets, n . 29; hypertensive . 105.9 +/- 10.4 nmol/10(11) platelets, n . 27; p less than 0.001). In the five families investigated, the lowered serotonin content was observed in some normotensive members. The reduced number of carriers of serotonin uptake and the slight decrease in the affinity constant observed in platelets of patients with essential hypertension suggest that serotonin metabolism is altered in essential hypertension and that blood platelets may be a useful model in studying the serotonergic modifications at the molecular level

Cost-effectiveness of hepatitis A vaccination for individuals with chronic hepatitis C.

Science.gov (United States)

Chapko, Michael K; Yee, Helen S; Monto, Alexander; Dominitz, Jason A

2010-02-17

The incidence of hepatitis A infection in the United States has decreased dramatically in recent years because of childhood immunization programs. A decision analysis of the cost-effectiveness of hepatitis A vaccination for adults with hepatitis C was conducted. No vaccination strategy is cost-effective for adults with hepatitis C using the recent lower anticipated hepatitis A incidence, private sector costs, and a cost-effectiveness criterion of $100,000/QALY. Vaccination is cost-effective only for individuals who have cleared the hepatitis C virus when Department of Veterans Affairs costs are used. The recommendation to vaccinate adults with hepatitis C against hepatitis A should be reconsidered. Published by Elsevier Ltd.

Hepatic folate metabolism in the chronic alcoholic monkey

International Nuclear Information System (INIS)

Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

1981-01-01

To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3 H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

Science.gov (United States)

Kim, Min-Hyun; Aydemir, Tolunay B; Kim, Jinhee; Cousins, Robert J

2017-07-18

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14 -/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.

Endurance training decreases the non-linearity in the oxygen uptake-power output relationship in humans.

Science.gov (United States)

Majerczak, Joanna; Korostynski, Michal; Nieckarz, Zenon; Szkutnik, Zbigniew; Duda, Krzysztof; Zoladz, Jerzy A

2012-03-01

In this study, we hypothesized that 5 weeks of cycling endurance training can decrease the magnitude of the non-proportional increase in oxygen uptake (V(O(2))) to power output relationship (V(O(2)) 'excess') at exercise intensities exceeding the lactate threshold (LT). Ten untrained, physically active men performed a bout of incremental cycling exercise until exhaustion before and after training. The mitochondrial DNA copy number, myosin heavy chain composition and content of uncoupling protein 3 and sarcoplasmic reticulum Ca(2+)-ATPases (SERCAs) were analysed in muscle biopsies taken from vastus lateralis before and after training. The training resulted in an enhancement of the power-generating capabilities at maximal oxygen uptake (V(O(2)max)) by ∼7% (P = 0.002) despite there being no changes in V(O(2)max) (P = 0.49). This effect was due to a considerable reduction in the magnitude of the V(O(2)) 'excess' (P 0.05) were found after training. We conclude that the training-induced increase in power-generating capabilities at V(O(2)max) was due to attenuation of the V(O(2)) 'excess' above the LT. This adaptive response seems to be related to the improvement of muscle metabolic stability, as judged by a lowering of plasma ammonia concentration. The enhancement of muscle metabolic stability after training could be caused by a decrease in ATP usage at a given power output owing to downregulation of SERCA2 pumps.

Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

Directory of Open Access Journals (Sweden)

Stephanie M Marshall

Full Text Available An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL support TICE, antisense oligonucleotides (ASO were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP, which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg mice, which predominantly excrete cholesterol via TICE, and wild type (WT littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

acceptance of hepatitis b vaccine by workers in a nigerian teaching

African Journals Online (AJOL)

hi-tech

2000-11-11

Nov 11, 2000 ... uptake of at least one dose of hepatitis B vaccine, and 'compliance' defined as the receipt of the three prescribed ... B infection within the hospital setting - doctors, nurses, and laboratory workers - showed the greatest apathy to ..... Dancocks, A., Hewitt, S. Hepatitis B immunisation status of A &. E healthcare ...

{sup 18}F-FDG PET/CT in Primary AL Hepatic Amyloidosis Associated with Multiple Myeloma

Energy Technology Data Exchange (ETDEWEB)

Son, Youn Mi; Bak, Cheol Hee [Seoul Medical Center, Seoul (Korea, Republic of); Choi, Joon Young; Cheon, Mi Ju; Kim, Young Eun; Lee, Kyung Han; Kim, Byung Tae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2011-10-15

We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased {sup 18}F-FDG uptake in the liver. Although there have been several case studies showing positive {sup 18}F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the {sup 18}F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously.

Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

Science.gov (United States)

Pillitteri, C A; Craig, L E

2013-01-01

Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

Science.gov (United States)

McClain, Donald A.; Abuelgasim, Khadega A.; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M.Celeste; Huang, Jingyu; Simcox, Judith A.; Yoon, Donghoon; Prchal, Josef T.; Gordeuk, Victor R.

2012-01-01

In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzymes genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHLR200W homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wildtype VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHLR200W homozygotes. We expanded these observations in VHLR200W homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc but not Pdk2 was decreased and skeletal muscle expression of Glut1, Pdk1 and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. PMID:23015148

Increasing Coverage of Hepatitis B Vaccination in China

OpenAIRE

Wang, Shengnan; Smith, Helen; Peng, Zhuoxin; Xu, Biao; Wang, Weibing

2016-01-01

Abstract This study used a system evaluation method to summarize China's experience on improving the coverage of hepatitis B vaccine, especially the strategies employed to improve the uptake of timely birth dosage. Identifying successful methods and strategies will provide strong evidence for policy makers and health workers in other countries with high hepatitis B prevalence. We conducted a literature review included English or Chinese literature carried out in mainland China, using PubMed, ...

Hepatitis C Virus Core Protein Decreases Lipid Droplet Turnover

Science.gov (United States)

Harris, Charles; Herker, Eva; Farese, Robert V.; Ott, Melanie

2011-01-01

Steatosis is a frequent complication of hepatitis C virus infection. In mice, this condition is recapitulated by the expression of a single viral protein, the nucleocapsid core. Core localizes to the surface of lipid droplets (LDs) in infected liver cells through a process dependent on host diacylglycerol acyltransferase 1 (DGAT1), an enzyme that synthesizes triglycerides in the endoplasmic reticulum. Whether DGAT1 also plays a role in core-induced steatosis is uncertain. Here, we show that mouse embryonic fibroblasts isolated from DGAT1−/− mice are protected from core-induced steatosis, as are livers of DGAT1−/− mice expressing core, demonstrating that the steatosis is DGAT1-dependent. Surprisingly, core expression did not increase DGAT1 activity or triglyceride synthesis, thus excluding the possibility that core activates DGAT1 to cause steatosis. Instead, we find that DGAT1-dependent localization of core to LDs is a prerequisite for the steatogenic properties of the core. Using biochemical and immunofluorescence microscopy techniques, we show that the turnover of lipids in core-coated droplets is decreased, providing a physiological mechanism for core-induced steatosis. Our results support a bipartite model in which core first requires DGAT1 to gain access to LDs, and then LD-localized core interferes with triglyceride turnover, thus stabilizing lipid droplets and leading to steatosis. PMID:21984835

Effects of 1,2-dibromo-3-chloropropane on hepatic heme synthesis

International Nuclear Information System (INIS)

Moody, D.E.; Clawson, G.A.; Piper, W.N.; Smuckler, E.A.

1984-01-01

Previous studies showed that 1,2-dibromo-3-chloropropane (DBCP) caused a decrease in hepatic microsomal cytochrome P-450 suggesting that hepatic heme metabolism may be affected by DBCP treatment. Various parameters of hepatic heme synthesis were measured at intervals ranging from 0 to 72 hr in male Sprague-Dawley rats given a single oral dose (200 mg/kg) of DBCP. Incorporation of the radiolabeled heme precursor [delta-14C]aminolevulinic acid (14C-ALA) into liver, protein, extracted heme, and subcellular fractions of liver homogenates was significantly decreased to 75, 58, and 81% of controls, respectively, at 24 hr. At 48 and 72 hr after DBCP treatment, the accumulation of 14C-ALA label after 4 hr in liver homogenates and subcellular fractions was significantly increased in comparison to controls. These changes in 14C-ALA uptake were accompanied by decreases in total liver and microsomal heme, but not mitochondrial heme. Decreases were found in the spectral content of two heme proteins, cytochromes P-450 and b5, and the activity of another heme protein, catalase. Heme oxygenase activity increased to 130, 151, 209, and 186% of control values at 12, 24, 48, and 72 hr after DBCP, respectively. A slight, but significant, increase in ALA-synthetase to 112% of controls occurred at 24 hr, and slight, but significant, decreases in ALA-dehydratase to 90 and 80% of control occurred at 12 and 24 hr, respectively. No significant changes in uroporphyrinogen-1-synthetase or ferrochelatase at the time points tested was noted. The porphyrin content of liver was increased to 130% of control, while the serum and urine porphyrin levels were decreased to 30% of the control values at 24 hr. Liver ALA content was not significantly altered through the time period studied, but serum and urine levels were increased at 24 hr to 176 and 130% of the control values, respectively. In conclusion, the decreases in liver heme proteins following a single oral dose of DBCP are accompanied by

Hepatic taurine transport: a Na+-dependent carrier on the basolateral plasma membrane

International Nuclear Information System (INIS)

Bucuvalas, J.C.; Goodrich, A.L.; Suchy, F.J.

1987-01-01

Highly purified rat basolateral liver plasma membrane vesicles were used examine the mechanism and the driving forces for hepatic uptake of the β-amino acid, taurine. An inwardly directed 100 mM NaCl gradient stimulated the initial rate of taurine uptake and energized a transient twofold accumulation of taurine above equilibrium (overshoot). In contrast, uptake was slower and no overshoot was detected in the presence of a KCl gradient. A negative intravesicular electrical potential generated by the presence of permeant anions or an outwardly directed K + gradient with valinomycin increased Na + -stimulated taurine uptake. External Cl - stimulated Na + -dependent taurine uptake independent of effects on the transmembrane electrical potential difference. Na + -dependent taurine uptake showed a sigmoidal dependence on extravesicular Na + concentration, suggesting multiple Na + ions are involved in the translocation of each taurine molecule. Na + -dependent taurine uptake demonstrated Michaelis-Menten kinetics with a maximum velocity of 0.537 nmol x mg protein -1 x min -1 and an apparent K/sub m/ of 174 μM. [ 3 H]taurine uptake was inhibited by the presence of excess unlabeled taurine, β-alanine, or hypotaurine but not by L-glutamine or L-alanine. In summary, using basolateral liver plasma membrane vesicles, the authors have shown that hepatic uptake of taurine occurs by a carrier-mediated, secondary active transport process specific for β-amino acids. Uptake is electrogenic, stimulated by external Cl - , and requires multiple Na + ions for the translocation of each taurine molecule

Branched-chain amino acids for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Koretz, R L; Kjaergard, L L

2003-01-01

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy....

Diagnostic pharmaco-scintigraphy with hepatic intra-arterial technetium-99m macroaggregated albumin in the determination of tumour to non-tumour uptake ratio in hepatocellular carcinoma

International Nuclear Information System (INIS)

Lau, W.Y.; Leung, T.W.T.; Chan, M.; Leung, N.W.Y.; Metreweli, C.; Li, A.K.C.

1994-01-01

Between October 1990 and March 1993, 124 patients with hepatocellular carcinoma (HCC) underwent diagnostic pharmaco-scintigraphy with hepatic intraarterial technetium-99m macroaggregated albumin (TcMAA) to determine the tumorous to non-tumorous liver tissue uptake ratio (T/N ratio). There were 110 males and 14 females. Ages ranged from 16 to 73 with a median of 55 years. The range of T/N ratio was 0.7 to 19.3 with a median of 3.8. 12 patients with inoperable HCC were subsequently selected by predetermined criteria to undergo treatment with hepatic intraarterial yttrium-90 microspheres and the T/N ratios in these patients were validated by beta probe dosimetry and liquid scintillation count of multiple liver biopsies. The T/N ratio determined by preoperative diagnostic TcMAA scan corrected well with intraoperative beta probe dosimetry, with coefficient of correlation r = 0.82. Preoperative TcMAA scan also correlated well with liquid scintillation count of biopsy specimens. (author)

Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

Energy Technology Data Exchange (ETDEWEB)

Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W. [Catholic University College of Medicine, Seoul (Korea, Republic of)

1994-03-15

Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on {sup 99m}Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

Radiocolloid Uptake in the Pancreas Islet Cell Tumor: Case Report

International Nuclear Information System (INIS)

Yang, W. J.; Chung, S. K.; Yeon, S. K.; Shinn, K. S.; Bahk, Y. W.

1994-01-01

Colloid uptake in various hepatic conditions such as focal nodular hyperplasia, regenerating nodular in the cirrhotic liver, hamartoma, hemangioma and rarely hepatoma has been documented. Extrahepatic tumors may show colloid uptake and they include splenic hemangioma, malignant fibrous histiocytoma, breast carcinoma and Kaposi's sarcoma. The mechanism of colloid uptake in those lesions is associated with phagocytic activity in or around the tumors. We report a pancreas islet cell tumor that showed colloid uptake on 99m Tc-phytate liver scan without histologic evidence of phagocytosis by tumor cells or infiltration of phagocytes in the tumor. Microscopically the tumor was highly vascular and showed diffuse hemorrhage throughout the tumor. We postulated that extravasation of the colloid into the tumor interstitium caused nonspecific colloid uptake in this tumor. It is expected that hemorrhagic tumor may show nonspecific colloid uptake without phagocytosis in or about the lesion.

188Re-SSS lipiodol: radiolabelling and biodistribution following injection into the hepatic artery of rats bearing hepatoma.

Science.gov (United States)

Garin, Etienne; Denizot, Benoit; Noiret, Nicolas; Lepareur, Nicolas; Roux, Jerome; Moreau, Myriam; Herry, Jean-Yves; Bourguet, Patrick; Benoit, Jean-Pierre; Lejeune, Jean-Jacques

2004-10-01

Although intra-arterial radiation therapy with 131I-lipiodol is a useful therapeutic approach to the treatment of hepatocellular carcinoma, various disadvantages limit its use. To describe the development of a method for the labelling of lipiodol with 188Re-SSS (188Re (S2CPh)(S3CPh)2 complex) and to investigate its biodistribution after injection into the hepatic artery of rats with hepatoma. 188Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 188Re, in cold lipiodol. The radiochemical purity (RCP) of labelling was checked immediately. The 188Re-SSS lipiodol was injected into the hepatic artery of nine rats with a Novikoff hepatoma. They were sacrificed 1, 24 and 48 h after injection, and used for ex vivo counting. Labelling of 188Re-SSS lipiodol was achieved with a yield of 97.3+/-2.1%. The immediate RCP was 94.1+/-1.7%. Ex vivo counting confirmed a predominantly hepatic uptake, with a good tumoral retention of 188Re-SSS lipiodol, a weak pulmonary uptake and a very faint digestive uptake. The 'tumour/non-tumoral liver' ratio was high at 1, 24 and 48 h after injection (2.9+/-1.5, 4.1+/-/4.1 and 4.1+/-0.7, respectively). Using the method described here, 188Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. The biodistribution in rats with hepatoma indicates a good tumoral retention of 188Re-SSS lipiodol associated with a predominant hepatic uptake, a weak pulmonary uptake and a very faint digestive uptake. This product should be considered for intra-arterial radiation therapy in human hepatoma.

Novel Index (Hepatic Receptor: IHR) to Evaluate Hepatic Functional Reserve Using (99m)Tc-GSA Scintigraphy.

Science.gov (United States)

Hasegawa, Daisuke; Onishi, Hideo; Matsutomo, Norikazu

2016-02-01

This study aimed to evaluate the novel index of hepatic receptor (IHR) on the regression analysis derived from time activity curve of the liver for hepatic functional reserve. Sixty patients had undergone (99m)Tc-galactosyl serum albumin ((99m)Tc-GSA) scintigraphy in the retrospective clinical study. Time activity curves for liver were obtained by region of interest (ROI) on the whole liver. A novel hepatic functional predictor was calculated with multiple regression analysis of time activity curves. In the multiple regression function, the objective variables were the indocyanine green (ICG) retention rate at 15 min, and the explanatory variables were the liver counts in 3-min intervals until end from beginning. Then, this result was defined by IHR, and we analyzed the correlation between IHR and ICG, uptake ratio of the heart at 15 minutes to that at 3 minutes (HH15), uptake ratio of the liver to the liver plus heart at 15 minutes (LHL15), and index of convexity (IOC). Regression function of IHR was derived as follows: IHR=0.025×L(6)-0.052×L(12)+0.027×L(27). The multiple regression analysis indicated that liver counts at 6 min, 12 min, and 27 min were significantly related to objective variables. The correlation coefficient between IHR and ICG was 0.774, and the correlation coefficient between ICG and conventional indices (HH15, LHL15, and IOC) were 0.837, 0.773, and 0.793, respectively. IHR had good correlation with HH15, LHL15, and IOC. The finding results suggested that IHR would provide clinical benefit for hepatic functional assessment in the (99m)Tc-GSA scintigraphy.

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

Science.gov (United States)

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.

Liver scintigraphy of fulminant hepatitis

International Nuclear Information System (INIS)

Tamaki, Nagara; Ishihara, Takashi; Mori, Toru

1980-01-01

The liver scintigraphies of five patients with fulminant hepatitis were examined. Scintiphotos using sup(99m)Tc-phytate were taken within two weeks after the onset. Scintiphotos of 12 normal subjects, 11 cases with acute hepatitis, 17 cases with liver cirrhosis were served as control. Their scintiphotos showed reduction of the size, well-maintained uptake, mostly homogenous RI distribution, and no left lobe enlargement, which could differentiate them from the chronic liver dysfunction. In one of the cases chronological changes in liver scintigraphy were observed. The size of the liver was reduced progressively until the 16th day and re-enlarged at the 30th day and thereafter. Three indices [S/W, (R + L)/W, and L/R] were calculated. S: area of liver, R or L: longitudinal length of the right or left lobe, W: body width. Relative size of the liver expressed by S/W or (R + L)/W showed significant reduction in fulminant hepatitis compared with acute hepatitis. However, they were not different significantly from those of normal subjects. Except for liver cirrhosis, L/R (left lobe swelling index) did not show significant differences among fulminant hepatitis, normal subjects, and acute hepatitis. These indices were also useful in follow-up study of the liver scintigraphy. The liver scintigraphy in the early phase of fulminant hepatitis seems to reflect the degree of massive hepatic necrosis. It is also useful to differentiate chronic hepatic failure. Apparant reduction in scintigraphical liver size seems to suggest poor prognosis, however, it should also kept in mind that the size of the liver in this condition might change quite rapidly and greatly. (author)

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

Directory of Open Access Journals (Sweden)

Wilmon F Grant

2011-02-01

Full Text Available To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD contained equivalent levels of n-3 fatty acids (FA's and higher levels of n-6 FA's than the control diet (CTR, we found significant decreases in docosahexaenoic acid (DHA and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

DEFF Research Database (Denmark)

Bendtsen, F; Christensen, N J; Sørensen, T I

1991-01-01

Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80...... to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained...

The Hepatitis C Genotype 1 Paradox: Cost per Treatment Is Increasing, but Cost per Cure Is Decreasing

Directory of Open Access Journals (Sweden)

Stephen D Shafran

2015-01-01

Full Text Available Significant attention has been focused on the perceived increase in the cost of antiviral treatment for hepatitis C genotype 1 infection since the approval of the first direct-acting antiviral agents in 2011. Using Canadian list prices, the present analysis points out a paradox: while the cost per antiviral regimen is increasing, the cost per cure is decreasing, especially with interferon-free therapy. In a publicly funded health care system, the lowest cost per cure is a more valuable measure of value for public money than the cost per regimen.

The hepatitis C genotype 1 paradox: cost per treatment is increasing, but cost per cure is decreasing.

Science.gov (United States)

Shafran, Stephen D

2015-01-01

Significant attention has been focused on the perceived increase in the cost of antiviral treatment for hepatitis C genotype 1 infection since the approval of the first direct-acting antiviral agents in 2011. Using Canadian list prices, the present analysis points out a paradox: while the cost per antiviral regimen is increasing, the cost per cure is decreasing, especially with interferon-free therapy. In a publicly funded health care system, the lowest cost per cure is a more valuable measure of value for public money than the cost per regimen.

Scintigraphic aspect of liver in hepatitis. [/sup 198/Au-radiocolloid

Energy Technology Data Exchange (ETDEWEB)

Silva, W M; Medeiros, M [Hospital dos Servidores do Estado, Rio de Janeiro (Brazil). Servico de Medicina Nuclear

1976-01-01

A series of scintigraphs was made in a group of 15 patients with viral hepatitis, and compared with biochemical tests. Although in some patients the last biochemical tests were only slightly elevated, and in others entirely normal, they all continued to show abnormal scintigraphs with a mottled aspect and splenic uptake. It is supposed that some sequellae remain in the hepatic tissue even though the patient responds well in clinical and laboratory tests.

Decreased blood hepatitis B surface antibody levels linked to e-waste lead exposure in preschool children

Energy Technology Data Exchange (ETDEWEB)

Xu, Xijin [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong (China); Chen, Xiaojuan; Zhang, Jian [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Guo, Pi [Department of Public Health, Shantou University Medical College, Shantou 515041, Guangdong (China); Fu, Tingzao; Dai, Yifeng [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China); Lin, Stanley L. [Department of Pathophysiology and Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, Guangdong (China); Huo, Xia, E-mail: xhuo@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, and Guangdong Provincial Key Laboratory of Infectious Diseases, Shantou University Medical College, Shantou 515041, Guangdong (China)

2015-11-15

Highlights: • Secondary exploratory analyses displayed a correlation of blood Pb to HBsAb levels. • Generalized linear mixed models were used to analyze two-phase data. • Children from an e-waste area had higher blood Pb levels and lower HBsAb titers. • Nearly 50% of Pb-exposed children fail to develop sufficient HBV immunity. • Different vaccination strategies are required for in e-waste areas. - Abstract: Lead (Pb) is a widespread environmental contaminant that can profoundly affect the immune system in vaccinated children. To explore the association between blood Pb and HBsAb levels in children chronically exposed to Pb, we measured hepatitis B surface antibody (HBsAb) titers, to reflect the immune response in the children of Guiyu, an electronic and electrical waste (e-waste) recycling area well known for environmental Pb contamination. We performed secondary exploratory analyses of blood Pb levels and plasma HBsAb titers in samples, taken in two phases between 2011 and 2012, from 590 children from Guiyu (exposed group) and Haojiang (reference group). Children living in the exposed area had higher blood Pb levels and lower HBsAb titers compared with children from the reference area. At each phase, generalized linear mixed models (GLMMs) showed that HBsAb titers were significantly negatively associated with child blood Pb levels. This work shows that a decreased immune response to hepatitis B vaccine and immune system might have potential harm to children with chronic Pb exposure. Importantly, nearly 50% of chronically exposed children failed to develop sufficient immunity to hepatitis in response to vaccination. Thus different vaccination strategies are needed for children living under conditions of chronic Pb exposure.

Decreased blood hepatitis B surface antibody levels linked to e-waste lead exposure in preschool children

International Nuclear Information System (INIS)

Xu, Xijin; Chen, Xiaojuan; Zhang, Jian; Guo, Pi; Fu, Tingzao; Dai, Yifeng; Lin, Stanley L.; Huo, Xia

2015-01-01

Highlights: • Secondary exploratory analyses displayed a correlation of blood Pb to HBsAb levels. • Generalized linear mixed models were used to analyze two-phase data. • Children from an e-waste area had higher blood Pb levels and lower HBsAb titers. • Nearly 50% of Pb-exposed children fail to develop sufficient HBV immunity. • Different vaccination strategies are required for in e-waste areas. - Abstract: Lead (Pb) is a widespread environmental contaminant that can profoundly affect the immune system in vaccinated children. To explore the association between blood Pb and HBsAb levels in children chronically exposed to Pb, we measured hepatitis B surface antibody (HBsAb) titers, to reflect the immune response in the children of Guiyu, an electronic and electrical waste (e-waste) recycling area well known for environmental Pb contamination. We performed secondary exploratory analyses of blood Pb levels and plasma HBsAb titers in samples, taken in two phases between 2011 and 2012, from 590 children from Guiyu (exposed group) and Haojiang (reference group). Children living in the exposed area had higher blood Pb levels and lower HBsAb titers compared with children from the reference area. At each phase, generalized linear mixed models (GLMMs) showed that HBsAb titers were significantly negatively associated with child blood Pb levels. This work shows that a decreased immune response to hepatitis B vaccine and immune system might have potential harm to children with chronic Pb exposure. Importantly, nearly 50% of chronically exposed children failed to develop sufficient immunity to hepatitis in response to vaccination. Thus different vaccination strategies are needed for children living under conditions of chronic Pb exposure

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.

Science.gov (United States)

Xu, Zhe-Rong; Li, Jin-You; Dong, Xin-Wei; Tan, Zhong-Ju; Wu, Wei-Zhen; Xie, Qiang-Min; Yang, Yun-Mei

2015-08-24

In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats

DEFF Research Database (Denmark)

Galbo, H; Saugmann, P; Richter, Erik

1979-01-01

Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other...

Seroprevalence of Hepatitis A Twelve Years After the Implementation of Toddlers' Vaccination: A Population-Based Study in Israel.

Science.gov (United States)

Bassal, Ravit; Weil, Merav; Cohen, Daniel; Sofer, Danit; Mendelson, Ella; Shohat, Tamy

2017-10-01

In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objective of the present study was to evaluate the seroprevalence of hepatitis A virus antibodies in the Israeli population before and after the introduction of the program. A cross-sectional serosurvey using the National Serum Bank was conducted on 1883 and 2027 serum samples collected before and after introduction of the vaccine, respectively. Serologic tests for the presence of hepatitis A IgG antibodies were performed using an automated enzyme-linked fluorescent assay. The age-adjusted seroprevalence rates of hepatitis A virus antibodies before implementation of hepatitis A vaccination program were 47.1% [95% confidence interval (CI): 44.7%-49.5%] among Jews and 82.8% (95% CI: 79.6%-85.9%) among Arabs, increasing 12 years after to 67.4% (95% CI: 64.7%-70.0%) and 88.2% (95% CI: 86.1%-90.2%), respectively. The seropositivity rate among Jews and Arabs increased significantly among the cohorts included in the program. However, among Jews, a significant increase in seropositivity was also detected among age groups not included in the vaccination program. The decrease in the incidence of hepatitis A in Israel is a consequence of high vaccine uptake, persistent seropositivity rates after vaccination and the considerable number of people vaccinated beyond the program.

Hepatic metabolism of toluene after gastrointestinal uptake in humans

DEFF Research Database (Denmark)

Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

1993-01-01

The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...

Increased serum cortisol binding in chronic active hepatitis

International Nuclear Information System (INIS)

Orbach, O.; Schussler, G.C.

1989-01-01

A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

Combining functional CT and FDG PET allows the calculation of FDG extraction fraction and hepatic glucose phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Griffiths, M R [Centre for Medical and Health Physics, Queensland University of Technology (Australia); Wesley Research Institute, QLD (Australia); Miles, K A [Centre for Medical and Health Physics, Queensland University of Technology (Australia); Wesley Research Institute, QLD (Australia); Southern X-ray Clinics, Brisbane [Australia; Keith, C J [Wesley Research Institute, QLD (Australia)

2002-09-01

Perfusion data from Functional CT and FDG-PET data may be combined to provide additional information about the uptake of FDG. We have developed methods to calculate FDG extraction fraction in tissues and to quantify hepatic glucose phosphorylation in the liver. Extraction fraction: Functional CT and FDG-PET studies were used to obtain measurements of perfusion and glucose uptake respectively within ten pulmonary nodules. The net influx constant (Ki) was determined from SUV measurements for each lung mass Extraction fraction (E) for each mass lesion was determined from: E=Ki/(Px[1-Hct]). A pixel by pixel calculation allowed generation of extraction fraction maps. The extraction fraction measurements ranged (median) from 0.6% to 4.81% (2.7%). The values for a benign nodule and an organising pneumonia were 0.6% and 0.71% respectively. Extraction fraction measurements for the malignant nodules ranged from 2.01% to 4.81%. A clearer separation of benign and malignant lesions is seen with E values rather than with SUV. Hepatic Glucose Phosphorylation: Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Hepatic perfusion and the net influx constant were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). By combining functional CT measurements of blood flow with PET measurements of FDG uptake, it is possible to calculate the extraction fraction of FDG and Hepatic glucose phosphorylation. The use of the extraction fraction has improved the distinction between malignant and

Combining functional CT and FDG PET allows the calculation of FDG extraction fraction and hepatic glucose phosphorylation

International Nuclear Information System (INIS)

Griffiths, M.R.; Miles, K.A.; Keith, C.J.

2002-01-01

Perfusion data from Functional CT and FDG-PET data may be combined to provide additional information about the uptake of FDG. We have developed methods to calculate FDG extraction fraction in tissues and to quantify hepatic glucose phosphorylation in the liver. Extraction fraction: Functional CT and FDG-PET studies were used to obtain measurements of perfusion and glucose uptake respectively within ten pulmonary nodules. The net influx constant (Ki) was determined from SUV measurements for each lung mass Extraction fraction (E) for each mass lesion was determined from: E=Ki/(Px[1-Hct]). A pixel by pixel calculation allowed generation of extraction fraction maps. The extraction fraction measurements ranged (median) from 0.6% to 4.81% (2.7%). The values for a benign nodule and an organising pneumonia were 0.6% and 0.71% respectively. Extraction fraction measurements for the malignant nodules ranged from 2.01% to 4.81%. A clearer separation of benign and malignant lesions is seen with E values rather than with SUV. Hepatic Glucose Phosphorylation: Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Hepatic perfusion and the net influx constant were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). By combining functional CT measurements of blood flow with PET measurements of FDG uptake, it is possible to calculate the extraction fraction of FDG and Hepatic glucose phosphorylation. The use of the extraction fraction has improved the distinction between malignant and

Hepatic blood flow with colloidal 198Au in the diagnosis of chronic hepatitis in children

International Nuclear Information System (INIS)

Marian, L.; Szantay, V.

1975-01-01

Tracer quantities of colloidal 198 Au were used to estimate the hepatic blood flow in normal children and in children with active or progressive chronic hepatitis and also to obtain scintigrams of the liver. In active chronic hepatitis a significant decrease in HBF values was observed, suggesting that the method may be used as a diagnostic criterion which is superior to hepatic scintigraphy. In progressive chronic hepatitis HBF values even lower than those in active hepatitis were observed. Together with more characteristic clinical findings and abnormal results of biochemical function tests, they underline the value of the method in estimating the severity and the evolution of the disease. (orig.) [de

Skeletal muscle glucose uptake during dynamic exercise in humans

DEFF Research Database (Denmark)

Richter, Erik; Kiens, Bente; Saltin, Bengt

1988-01-01

uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted......To study the role of muscle mass in glucoregulation, six subjects worked with the knee extensors of one leg on a specially constructed cycle ergometer. The knee extensors of one leg worked either alone or in combination with the knee extensors of the other leg and/or with the arms. Substrate usage...... to net lactate uptake. Decreased glucose uptake could not be explained by decreased perfusion. It is concluded that thigh muscle glucose uptake is affected by the size of the total muscle mass engaged in exercise. The decrease in thigh glucose uptake, when arm cranking was added and O2 uptake...

Hepatic nuclear sterol regulatory binding element protein 2 abundance is decreased and that of ABCG5 increased in male hamsters fed plant sterols.

Science.gov (United States)

Harding, Scott V; Rideout, Todd C; Jones, Peter J H

2010-07-01

The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P 6-fold (P = 0.029) and >2-fold (P sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis.

Limited but increasing use of treatment for hepatitis C across Europe in patients coinfected with HIV and hepatitis

DEFF Research Database (Denmark)

Mocroft, A; Rockstroh, J; Soriano, V

2006-01-01

Uptake of hepatitis C (HCV) treatment in HIV-coinfected patients is not well described. Of 2356 HCV-seropositive patients, 180 (7.6%) started HCV treatment with interferon-based therapies. In multivariate Poisson-regression models, there was a 38% increase per year in the incidence of starting HCV...... treatment (95% CI 26 - 51%, ppatients, it remains infrequent and variable...

Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

Science.gov (United States)

Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

2000-03-01

Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

Exenatide improves both hepatic and adipose tissue insulin resistance: A dynamic positron emission tomography study.

Science.gov (United States)

Gastaldelli, Amalia; Gaggini, Melania; Daniele, Giuseppe; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Iozzo, Patricia

2016-12-01

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. Fifteen male subjects (age = 56 ± 8 years; body mass index = 29 ± 1 kg/m 2 ; A1c = 5.7 ± 0.1%) were studied on two occasions, with a double-blind subcutaneous injection of EX (5 μg) or placebo (PLC) 30 minutes before a 75-g oral glucose tolerance test (OGTT). During OGTT, we measured hepatic (HGU) and adipose tissue (ATGU) glucose uptake with [ 18 F]2-fluoro-2-deoxy-D-glucose/positron emission tomography, lipolysis (RaGly) with [U- 2 H 5 ]-glycerol, oral glucose absorption (RaO) with [U- 13 C 6 ]-glucose, and hepatic glucose production (EGP) with [6,6- 2 H 2 ]-glucose. Adipo-IR and Hep-IR were calculated as (FFA 0-120min ) × (Ins 0-120min ) and (EGP 0-120min ) × (Ins 0-120min ), respectively. EX reduced RaO, resulting in reduced plasma glucose and insulin concentration from 0 to 120 minutes postglucose ingestion. EX decreased Hep-IR (197 ± 28 to 130 ± 37; P = 0.02) and increased HGU of orally administered glucose (23 ± 4 to 232 ± 89 [μmol/min/L]/[μmol/min/kg]; P = 0.003) despite lower insulin (23 ± 5 vs. 41 ± 5 mU/L; P < 0.02). EX enhanced insulin suppression of RaGly by decreasing Adipo-IR (23 ± 4 to 13 ± 3; P = 0.009). No significant effect of insulin was observed on ATGU (EX = 1.16 ± 0.15 vs. PLC = 1.36 ± 0.13 [μmol/min/L]/[μmol/min/kg]). Acute EX administration (1) improves Hep-IR, decreases EGP, and enhances HGU and (2) reduces Adipo-IR, improves the antilipolytic effect of insulin, and reduces plasma free fatty acid levels during OGTT. (Hepatology 2016;64:2028-2037). © 2016 by the American Association for the Study of Liver Diseases.

The interactive effects of a gradual temperature decrease and long-term food deprivation on cardiac and hepatic blood flows in rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

Petersen, L H; Dzialowski, E; Huggett, D B

2011-11-01

The aim of the present study was to determine the extent to which the fish liver is perfused with blood. Transonic® flow probes were therefore implanted around the ventral aorta and hepatic vein(s) to record baseline blood flows in rainbow trout (Oncorhynchus mykiss) previously held under two different feeding regimes (food-deprived or fed to satiation, 8-12 weeks). Fish from both groups were exposed to a gradual temperature decrease (12°C to 5°C) and physical disturbance. Cardiac output (Q), stroke volume (Sv) and hepatic venous blood flow (HVBF) were significantly reduced in food-deprived trout at 12°C. Heart rate was not significantly affected by nutritional status, but was significantly reduced when temperature was decreased to 5°C. Physically disturbing each fish at 12°C and 5°C showed that the performance capacity of the heart was not affected by food deprivation as the capacity to increase Q and Sv was not reduced in the food-deprived group. Overall this study showed that food deprivation in rainbow trout reduced cardiac and hepatic blood flows. However, long-term food deprivation did not affect the capacity of the heart to acutely increase performance. Copyright © 2011. Published by Elsevier Inc.

99mTc-DPD uptake in juvenile arthritis

International Nuclear Information System (INIS)

Stender Hansen, E.; Holm, I.E.; Buenger, C.; Knudsen, V.; Noer, I.; Bach Christensen, S.

1986-01-01

Unilateral arthritis of the knee was induced in mongrel puppies by intraarticular injections of 1% Carragheenan. Bone metabolism was studied by a scintimetric technique on static 99m Tc-diphosphonate bone scans every 2nd week during the induction of arthritis for 3 months and monthly in a postarthritic phase of another 3 months. Changes in uptake of radionuclide were present after 2 weeks. The induction phase was characterized by a decreased uptake in the calcification layer of the juxta-articular growth plates and a moderately increased epiphyseal uptake. The postarthritic phase was characterized by normalization of growth plate uptake and a marked increase in epiphyseal uptake. Using contact autoradiography, the epiphyseal uptake was seen mainly in a narrow subchondral and subsynovial bone layer, around bone cysts and osteophytes, whereas central epiphyseal bone was osteopenic with decreased uptake of tracer. The study suggests that the early scintigraphic appearance of juvenile non-suppurative arthritis may be an overall decrease in uptake of 99m Tc-diphosphonate due to a depression of growth plate metabolism. (author)

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway

Directory of Open Access Journals (Sweden)

Zhe-Rong Xu

2015-08-01

Full Text Available In this study, we examined the effects of apple polyphenols (APs on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE−/− mice were fed a western-type diet and orally treated with APs (100 mg/kg or atorvastatin (10 mg/kg for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL cholesterol and markedly up-regulated the glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs. Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

Diagnostic Accuracy 99mTc-DISIDA Scintigraphy in Biliary Atresia

International Nuclear Information System (INIS)

Hyun, In Young; Lee, Dong Soo; Lee, Kyung Han; Kim, Jong Ho; Chung, June Key; Suh, Jung Key; Lee, Myung Chul; Koh, Chang Soon

1994-01-01

We evaluated the diagnostic accuracy of 99m Tc-DISIDA scintigraphy as a mean of differentiating biliary atresia from neonatal hepatitis. 99m Tc-DISIDA scintigraphy was visually interpreted by assessing the presence or absence of radioactivity in the intestine or gall bladder. In patients without intestinal radioactivity, we measured the hepatic retention index and the hepatic uptake index. The hepatic retention index was expressed as the amount of change of liver activity from 5 minutes to 30 minutes postinjection. The hepatic uptake index was graded visually with 5 minute images using the following scoring scheme :grade 0 (normal hepatic uptake), grade 1 (decreased hepatic up take), grade 2 (hepatic uptake equal to cardiac uptake), and grade 3 (hepatic uptake less than cardiac uptake). Age, total bilirubin, and hepatic uptake index were compared between the biliary atresia and the neonatal hepatitis group, between neonatal hepatitis patients with and without intestinal radioactivity, and between the biliary atresia and neonatal hepatitis patients with absent intestinal radioactivity. The results were as follows : l) None of the 30 biliary atresia patients showed intestinal radioactivity, while 31/40 neonatal hepatitis patients showed intestinal radioactivity. The sensitivity, specificity, and accuracy of the presence of intestinal radioactivity or the diagnosis of biliary atresia was 100%, 78%, and 87%, respectively. 2) In patients with absent intestinal radioactivity the mean hepatic retention index was 1.5 ± 0.6 in the 16 biliary atresia patient,s, and 1.1 ± 0.2 in the 7 neonatal hepatitis patients(p 99m Tc-DISIDA scintigraphy is accurate in the differential diagnosis of biliary atresia and neonatal hepatitis. In patients without intestinal radioactivity, the hepatic retention index and hepatic uptake index, along with the patients age and total bilirubin level may supplement diagnosis and improve diagnostic accuracy.

Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept.

Science.gov (United States)

Bural, Gonca G; Torigian, Drew A; Burke, Anne; Houseni, Mohamed; Alkhawaldeh, Khaled; Cucchiara, Andrew; Basu, Sandip; Alavi, Abass

2010-06-01

The aim of this study was to compare hepatic standardized uptake values (SUVs) and hepatic metabolic volumetric products (HMVP) between patients of diffuse hepatic steatosis and control subjects with normal livers. Twenty-seven subjects were included in the study (13 men and 14 women; age range, 34-72 years). All had 18F-2-fluoro-2-D-deoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) scans with an interscan interval of 0-5 months. Twelve of 27 subjects had diffuse hepatic steatosis on MRI. The remaining 15 were selected as age-matched controls based on normal liver parenchyma on MRI. Mean and maximum hepatic SUVs were calculated for both patient groups on FDG-PET images. Hepatic volumes were measured from MRI. HMVP in each subject was subsequently calculated by multiplication of hepatic volume by mean hepatic SUV. HMVPs as well as mean and maximum hepatic SUVs were compared between the two study groups. HMVPs, mean hepatic SUVs, and maximum hepatic SUVs were greater (statistically significant, p < 0.05) in subjects with diffuse hepatic steatosis compared to those in the control group. The increase in HMVP is the result of increased hepatic metabolic activity likely related to the diffuse hepatic steatosis. The active inflammatory process related to the diffuse hepatic steatosis is the probable explanation for the increase in hepatic metabolic activity on FDG-PET study.

Hepatitis B Virus Vaccination Status of Laboratory Workers in ...

African Journals Online (AJOL)

This study aimed to evaluate the frequency of Hepatitis B virus vaccine uptake among medical laboratory workers (Scientists, technicians and phlebotomists) practicing in hospitals in Warri, Delta state, Nigeria. This was a cross-sectional descriptive study. Informed consent was received from subjects before inclusion in the ...

Limited but increasing use of treatment for hepatitis C across Europe in patients coinfected with HIV and hepatitis

DEFF Research Database (Denmark)

Mocroft, A; Rockstroh, J; Soriano, V

2006-01-01

Uptake of hepatitis C (HCV) treatment in HIV-coinfected patients is not well described. Of 2356 HCV-seropositive patients, 180 (7.6%) started HCV treatment with interferon-based therapies. In multivariate Poisson-regression models, there was a 38% increase per year in the incidence of starting HCV...... treatment (95% CI 26 - 51%, pHIV-coinfected patients, it remains infrequent and variable...

The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.

Science.gov (United States)

Flisiak, Robert; Horban, Andrzej; Gallay, Philippe; Bobardt, Michael; Selvarajah, Suganya; Wiercinska-Drapalo, Alicja; Siwak, Ewa; Cielniak, Iwona; Higersberger, Jozef; Kierkus, Jarek; Aeschlimann, Christian; Grosgurin, Pierre; Nicolas-Métral, Valérie; Dumont, Jean-Maurice; Porchet, Hervé; Crabbé, Raf; Scalfaro, Pietro

2008-03-01

Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.

18F-FDG PET/CT Equivalent of the Hepatic Hot Spot Sign With CT Correlation.

Science.gov (United States)

Jundt, Michael C; Broski, Stephen M; Binkovitz, Larry A

2018-05-01

A 43-year-old woman presented with an FDG-avid mediastinal Ewing sarcoma invading and nearly occluding the superior vena cava. Geographic increased FDG uptake in hepatic segment IVA was the only other site of nonphysiologic FDG activity. This focal activity was without an underlying mass, had atypical morphology for a hepatic metastasis, and correlated well with prior CT findings of abnormal segment IVA enhancement resulting from the recruitment of portocaval collaterals. In the correct setting, the F-FDG hepatic hot spot should be considered in the differential of a focal FDG-avid hepatic lesion in segment IVA.

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

International Nuclear Information System (INIS)

Lenoir, Laurence; Garin, Etienne; Edeline, Julien; Rolland, Yann; Pracht, Marc; Raoul, Jean-Luc; Ardisson, Valerie; Bourguet, Patrick; Clement, Bruno; Boucher, Eveline

2012-01-01

Identifying gastroduodenal uptake of 99m Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind. (orig.)

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

Energy Technology Data Exchange (ETDEWEB)

Lenoir, Laurence; Garin, Etienne [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); University of Rennes 1, Rennes (France); Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Rolland, Yann [Comprehensive Cancer Institute Eugene Marquis, Department of Medical Imaging, CS 44229, Rennes (France); Pracht, Marc [Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France); Raoul, Jean-Luc [Comprehensive Cancer Institute Paoli Calmette, Department of Medical Oncology, Marseille (France); Ardisson, Valerie [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); Bourguet, Patrick [Comprehensive Cancer Institute Eugene Marquis, Department of Nuclear Medicine, CS 44229, Rennes (France); University of Rennes 1, Rennes (France); Clement, Bruno [Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Boucher, Eveline [Liver Metabolisms and Cancer, INSERM, U-991, Rennes (France); Comprehensive Cancer Institute Eugene Marquis, Department of Medical Oncology, CS 44229, Rennes (France)

2012-05-15

Identifying gastroduodenal uptake of {sup 99m}Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind. (orig.)

Decreased miR-106a inhibits glioma cell glucose uptake and proliferation by targeting SLC2A3 in GBM.

Science.gov (United States)

Dai, Dong-Wei; Lu, Qiong; Wang, Lai-Xing; Zhao, Wen-Yuan; Cao, Yi-Qun; Li, Ya-Nan; Han, Guo-Sheng; Liu, Jian-Min; Yue, Zhi-Jian

2013-10-14

MiR-106a is frequently down-regulated in various types of human cancer. However the underlying mechanism of miR-106a involved in glioma remains elusive. The association of miR-106a with glioma grade and patient survival was analyzed. The biological function and target of miR-106a were determined by bioinformatic analysis and cell experiments (Western blot, luciferase reporter, cell cycle, ntracellular ATP production and glucose uptake assay). Finally, rescue expression of its target SLC2A3 was used to test the role of SLC2A3 in miR-106a-mediated cell glycolysis and proliferation. Here we showed that miR-106a was a tumor suppressor miRNA was involved in GBM cell glucose uptake and proliferation. Decreased miR-106a in GBM tissues and conferred a poor survival of GBM patients. SLC2A3 was identified as a core target of miR-106a in GBM cells. Inhibition of SLC2A3 by miR-106a attenuated cell proliferation and inhibited glucose uptake. In addition, for each biological process we identified ontology-associated transcripts that significantly correlated with SLC2A3 expression. Finally, the expression of SLC2A3 largely abrogated miR-106a-mediated cell proliferation and glucose uptake in GBM cells. Taken together, miR-106a and SLC2A3 could be potential therapeutic approaches for GBM.

Estimation of the Arterial Fraction of Total Hepatic Flow from Radionuclide Angiogram Using 99mTc-DISIDA

International Nuclear Information System (INIS)

Lee, Hae Gin; Lim, Gye Yeon; Yang, Il Kwon; Kim, Hack Hee; Lim, Jung Ik; Bahk, Yong Whee; Han, Sok Won; Han, Nam Ik; Lee, Young Sok

1991-01-01

Arterial fraction of total hepatic blood flow was estimated by a new method, slope method, on radionuclide angiogram using 99m Tc-DISIDA and was compared with that from 99m Tc-Phytate radionuclide angiogram. This study included 11 of normal subjects, 37 of intermediate group with various liver diseases, and 25 patients with liver cirrhosis. We analyzed the data with slope method from radionuclide angiograms and the results were compared with hepatic arterial fractions from uptake method, introduced by Lee et al. at 1986. The hepatic arterial fractions from radionuclide angiograms using 99m Tc-DISIDA and 99m Tc- Phytate were 0.32 ± 0.09 and 0.31 ± 0.11 respectively in normal subjects, and 0.75 ± 0.18 and 0.77 ± 0.21 respectively in patients with liver cirrhosis. The hepatic arterial fractions by the slope method was well correlated with those of the uptake method on 99m Tc-DISIDA scan. There was high correlation between the hepatic arterial fractions from 99m Tc-DISIDA and 99m Tc-Phytate scans. Hepatic arterial fraction estimated by the slope method is a useful index for the diagnosis of liver cirrhosis and the evaluation of status of portal hypertension.

Control of Hepatic Glucose Metabolism by Islet and Brain

Science.gov (United States)

Rojas, Jennifer M.; Schwartz, Michael W.

2014-01-01

Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

Influence of zinc on the biokinetics of Zn-65 and hepatic trace elements of ethanol treated rats

International Nuclear Information System (INIS)

Dhawan, D.K.; Pathak, A.; Pathak, R.; Mahmood, A.

2002-01-01

Influence of zinc on the biokinetics of 65 Zn and hepatic trace elements of ethanol treated rats. The effect of zinc on the biokinetics of 65 Zn in liver and whole body and its relation to the hepatic levels of different elements was evaluated in male wistar rats under alcoholic conditions. The rats were segregated into four treatment groups viz., normal control, ethanol treated, zinc treated and combined zinc+ethanol treated. Animals were fed 3ml of 30% ethanol orally daily and zinc in the form of zinc sulfate (ZnSo 4 7H 2 O) was administrated to rats at a dose level of 227mg/L mixed in their drinking water for a total duration of 2 months. Whole body counting studies indicated that the Tb 1 i.e., the faster elimination of the radiotracer. On the contrary, Tb 2 i.e., the slower component was increased significantly following ethanol treatment. Percent uptake values of 65 Zn were found to be increased in liver, intestine, muscle and kidney and decreased in bone under alcoholic conditions. A significant elevation was noticed in in vitro uptake 65 Zn in ethanol treated animals. In the above said conditions, the values were reverted back to within normal limits upon zinc supplementation to these ethanol intoxicated animals, except in the case of in vitro 65 Zn uptake in liver where the uptake was further increased upon combined treatment. A significant decrease in zinc contents was noticed in ethanol treated rats, which however were raised to normal levels upon zinc supplementation. Copper levels, on the other hand, were found to be significantly enhanced in both ethanol fed and combined ethanol+zinc supplemented animals. Calcium levels were found to e significantly decreased in both ethanol and zinc treated rats, which however were further reduced upon zinc supplementation to ethanol fed rats. However, no significant change was observed in the concentrations of sodium and potassium in any of the treatment groups. Therefore, zinc appears to play a protective role by

Computed tomography in hepatic trauma

International Nuclear Information System (INIS)

Moon, K.L. Jr.; Federle, M.P.

1983-01-01

Twenty-five patients with hepatic injury from blunt upper abdominal trauma were examined by computed tomography (CT). The spectrum of CT findings was recorded, and the size of the hepatic laceration and the associated hemoperitoneum were correlated with the mode of therapy used in each case (operative vs nonoperative). While the need for surgery correlated roughly with the size of the hepatic laceration, the size of the associated hemoperitoneum was an important modifying factor. Fifteen patients with hepatic lacerations but little or no hemoperitoneum were managed nonoperatively. CT seems to have significant advantages over hepatic scintigraphy, angiography, and diagnostic peritoneal lavage. By combining inforamtion on the clinical state of the patient and CT findings, therapy of hepatic injury can be individualized and the incidence of nontherapeutic laparotomies decreased

Drug-induced hepatic injury

DEFF Research Database (Denmark)

Friis, Henrik; Andreasen, P B

1992-01-01

The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.......5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.......7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected...

Tumor cytotoxicity by endothelial cells. Impairment of the mitochondrial system for glutathione uptake in mouse B16 melanoma cells that survive after in vitro interaction with the hepatic sinusoidal endothelium.

Science.gov (United States)

Ortega, Angel L; Carretero, Julian; Obrador, Elena; Gambini, Juan; Asensi, Miguel; Rodilla, Vicente; Estrela, José M

2003-04-18

High GSH content associates with high metastatic activity in B16-F10 melanoma cells cultured to low density (LD B16M). GSH homeostasis was investigated in LD B16M cells that survive after adhesion to the hepatic sinusoidal endothelium (HSE). Invasive B16M (iB16M) cells were isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sorting. HSE-derived NO and H(2)O(2) caused GSH depletion and a decrease in gamma-glutamylcysteine synthetase activity in iB16M cells. Overexpression of gamma-glutamylcysteine synthetase heavy and light subunits led to a rapid recovery of cytosolic GSH, whereas mitochondrial GSH (mtGSH) further decreased during the first 18 h of culture. NO and H(2)O(2) damaged the mitochondrial system for GSH uptake (rates in iB16M were approximately 75% lower than in LD B16M cells). iB16M cells also showed a decreased activity of mitochondrial complexes II, III, and IV, less O(2) consumption, lower ATP levels, higher O(2) and H(2)O(2) production, and lower mitochondrial membrane potential. In vitro growing iB16M cells maintained high viability (>98%) and repaired HSE-induced mitochondrial damages within 48 h. However, iB16M cells with low mtGSH levels were highly susceptible to TNF-alpha-induced oxidative stress and death. Therefore depletion of mtGSH levels may represent a critical target to challenge survival of invasive cancer cells.

Opt-Out Panel Testing for HIV, Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study.

Directory of Open Access Journals (Sweden)

Sarah O'Connell

Full Text Available Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.An opt-out ED blood borne virus screening programme was piloted from March 2014 to January 2015. Patients undergoing blood sampling during routine clinical care were offered HIV 1&2 antibody/antigen assay, HBV surface antigen and HCV antibody tests. Linkage to care where necessary was co-ordinated by the study team. New diagnosis and prevalence rates were defined as the new cases per 1000 tested and number of positive tests per 1000 tested respectively.Over 45 weeks of testing, of 10,000 patient visits, 8,839 individual patient samples were available for analysis following removal of duplicates. A sustained target uptake of >50% was obtained after week 3. 97(1.09%, 44(0.49% and 447(5.05% HIV, Hepatitis B and Hepatitis C tests were positive respectively. Of these, 7(0.08%, 20(0.22% and 58(0.66% were new diagnoses of HIV, Hepatitis B and Hepatitis C respectively. The new diagnosis rate for HIV, Hepatitis B and Hepatitis C was 0.8, 2.26 and 6.5 per 1000 and study prevalence for HIV, Hepatitis B and Hepatitis C was 11.0, 5.0 and 50.5 per 1000 respectively.Opt-out blood borne viral screening was feasible and acceptable in an inner-city ED. Blood borne viral infections were prevalent in this population and newly diagnosed cases were diagnosed and linked to care. These results suggest widespread blood borne viral testing in differing clinical locations with differing population demographic risks may be warranted.

Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

NARCIS (Netherlands)

Bahr, Matthias J.; Boeker, Klaus H. W.; Manns, Michael P.; Tietge, Uwe J. F.

Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis.

Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

Science.gov (United States)

Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

2017-06-03

Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

Science.gov (United States)

Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

2017-08-01

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

Science.gov (United States)

Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

2016-01-15

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

Effect of Green Tea Extract Encapsulated Into Chitosan Nanoparticles on Hepatic Fibrosis Collagen Fibers Assessed by Atomic Force Microscopy in Rat Hepatic Fibrosis Model.

Science.gov (United States)

Safer, Abdel-Majeed A; Hanafy, Nomany A; Bharali, Dhruba J; Cui, Huadong; Mousa, Shaker A

2015-09-01

The present study examined the effect of Green Tea Extract (GTE) encapsulated into Chitosan Nanoparticles (CS-NPs) on hepatic fibrosis in rat model as determined by atomic force microscopy (AFM). The bioactive compounds in GTE encapsulated into CS-NPs were determined using LC-MS/MS method. Additionally, the uptake of GTE-CS NPs in HepG2 cells showed enhanced uptake. In experimental fibrosis model, AFM was used as a high resolution microscopic tool to investigate collagen fibers as an indicator of hepatic fibrosis induced by treatment with CCl4. Paraffin sections of fibrotic liver tissues caused by CC4 treatment of rats and the effect of GTE-CS NPs treatment with or without CCl4 on hepatic fibrosis were examined. Liver tissues from the different groups of animals were de-waxed and processed as for normal H/E staining and Masson's trichrome staining to locate the proper area of ECM collagen in the CCl4 group versus collagen in liver tissues treated with the GTE-CS NPs with or without CCl4. Selected areas of paraffin sections were trimmed off and fixed flat on top of mica and inserted in the AFM stage. H/E staining, Masson's trichrome stained slides, and AFM images revealed that collagen fibers of 250 to 300 nm widths were abundant in the fibrotic liver samples while those of GTE-CS NPs were clear as in the control group. Data confirmed the hypothesis that GTE-CS NPs are effective in removing all the extracellular collagen caused by CCl4 in the hepatic fibrosis rat liver.

Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

Science.gov (United States)

Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

2012-04-15

A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun [Pusan National Univ. Hospital, Busan (Korea, Republic of)

2014-06-15

Although diffuse splenic {sup 18}F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma

International Nuclear Information System (INIS)

Kim, Keunyoung; Kim, Seongjang; Kim, Injoo; Kim, Dong Uk; Kim, Heeyoung; Kim, Sojung; Ahn, Sang Hyun

2014-01-01

Although diffuse splenic 18 F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p <0.001) and white blood cell count (p =0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p <0.001) and the hematocrit (p <0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET

18F-FAC PET selectively images hepatic infiltrating CD4 and CD8 T cells in a mouse model of autoimmune hepatitis.

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Salas, Jessica R; Chen, Bao Ying; Wong, Alicia; Cheng, Donghui; Van Arnam, John S; Witte, Owen N; Clark, Peter M

2018-04-26

Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation ( 18 F-FDG and 18 F-FAC) and hepatocyte biology ( 18 F-DFA) can visualize and quantify hepatic infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with Concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with 18 F-FDG, 18 F-FAC, and 18 F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis or vehicle were imaged with 18 F-FDG, 18 F-FAC, and 18 F-DFA PET. 18 F-FAC PET was performed on mice treated with ConA, and vehicle or dexamethasone. Biopsy samples of patients suffering from autoimmune hepatitis were immunostained for deoxycytidine kinase (dCK). Results: Hepatic accumulation of 18 F-FDG and 18 F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of 18 F-DFA was 41% lower in a mouse model of autoimmune hepatitis compared to control mice. Increased hepatic 18 F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic 18 F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic 18 F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic 18 F-FDG accumulation by 109% and decreased hepatic 18 F-DFA accumulation by 20% but had no effect on hepatic 18 F-FAC accumulation (non-significant 2% decrease). 18 F-FAC PET provided a non-invasive biomarker of the efficacy of

Hepatic resection and regeneration. Past and present

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Hatsuse, Kazuo

2007-01-01

Hepatic surgery has been performed on condition that the liver regenerates after hepatic resection, and the development of liver anatomy due to Glisson, Rex, and Couinaud has thrown light on hepatic surgery Understanding of feeding and drainage vessels became feasible for systemic hepatic resection; however, it seems to have been the most important problem to control the bleeding during hepatic resection. New types of devices such as cavitron ultrasonic surgical aspirator (CUSA) and Microwave coagulation were exploited to control blood loss during hepatic surgery. Pringle maneuver for exclusion feeding vessels of the liver and the decrease of central venous pressure during anesthesia enabled further decrease of blood loss. Nowadays, 3D-CT imaging may depict feeding and drainage vessels in relation to liver mass, and surgeons can simulate hepatic surgery in virtual reality before surgery, allowing hepatectomy to be performed without blood transfusion. Thus, hepatic resection has been a safe procedure, but there's been a significant research on how much of the liver can be resected without hepatic failure. A prediction scoring system based on ICGR15, resection rates, and age is mostly reliable in some criteria. Even if hepatectomy is performed with a good prediction score, the massive bleeding and associated infection may induce postoperative hepatic failure, while the criteria of postoperative hepatic failure have not yet established. Hepatic failure is supposed to be induced by the apoptosis of mature hepatocytes and necrosis originated from microcirculation disturbance of the liver. Prostaglandin E1 for the improvement of microcirculation, steroid for the inhibition of cytokines inducing apoptosis, and blood purification to exclude cytokines have been tried separately or concomitantly. New therapeutic approaches, especially hepatic regeneration from the stem cell, are expected. (author)

Effects of salt stress on phosphorus uptake by european rape sheiaralle

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Li Guihua; Zhang Jianfeng; Wei Dongpu; Yang Juncheng; Mei Yong

2007-01-01

The effects of different salinity on phosphorus uptake by European rape Sheiaralle were studied under hydroponics and sand culture conditions. The results showed that above ground uptake of instant P increased with the salinity increased, the uptake of 32 P by roots firstly decreased and then increased with the increase salinity. Instant P uptake by Brassica napus was lower under different salinity treatment than in non-saline condition (P - , but the biomass yield decreased much faster than P uptake, so P relatively condensed, and uptake of P by Brassica napus increased as the salinity (including non-saline treatment) was increased (P<0.05). Fresh weight of Brassica napus decreased significantly with the salinity increased (P<0.05). (authors)

Time trends in pediatric hospitalizations for hepatitis A in Greece (1999–2013): Assessment of the impact of universal infant immunization in 2008

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Papaevangelou, V.; Alexopoulou, Z.; Hadjichristodoulou, C.; Kourlamba, G.; Katsioulis, A.; Theodoridou, K.; Spoulou, V.; Theodoridou, M.

2016-01-01

ABSTRACT Hepatitis A vaccine was introduced in the Greek National Immunization Program in 2008. To estimate possible impact of the universal vaccination implementation, time trends of hospitalizations for hepatitis A at the Infectious Diseases Unit of a Tertiary Pediatric Hospital in Athens during 1999–2013 were analyzed. Hepatitis A hospitalizations were recorded from the discharge database and were expressed as frequencies and rate of annual departmental hospitalizations. Time series analysis (ARIMA) was used to explore trends and the impact of the vaccination. Moreover, changes in patient age, population group distribution and the duration of hospitalization were also examined. Hepatitis A hospitalizations rate significantly decreased between pre-vaccination (1999–2008) and post-vaccination (2009–2013) era from 50.5 to 20.8/1000 hospitalizations (p = 0.005). A 3-year periodicity and a trend of reduction on hepatitis A hospitalizations rates across years were noted. Roma children had significant higher rates of hepatitis A hospitalization, followed by immigrant children. Importantly, possibly due to preceding vaccine availability with considerable uptake in private market and unvaccinated group/pockets of children (Roma), overall vaccination effect was less apparent when compared to data from other countries that implemented universal vaccination. No significant change in patient age, population group distribution, or duration of hospitalization was observed. High risk groups such as Roma children should be targeted for vaccination to reduce future outbreaks. PMID:27141813

Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat.

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Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua

2015-03-01

Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

Role of organic phosphorous in diagnosis of viral hepatitis patients B and C

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Ahmed, A.M.; Abdel Aziz, S.M.; El Sherbin, E.M.

2002-01-01

Biochemical and radiochemical analysis were performed on blood of egyptian men infected with hepatitis B, C and mixed B and C viruses as well as normal controls. The results revealed remarkable significant and very highly significant increases in ALT and AST activities in all patient groups. Regarding ALP enzyme, it showed significant increases in hepatitis C (Gr.III) and mixed hepatitis B and C (Gr. IV), whereas it showed a highly significant decrease in hepatitis B virus (Gr.II). GGT activity was highly significantly increased in Gr.II and Gr.III while non-significant change in Gr.IV was detected. Some biochemical compounds in blood especially phosphorus might taken as an early diagnostic tool for hepatitis phosphorus might taken as an early diagnostic tool for hepatitis B and C viruses. Inorganic phosphorus showed very high significant decreases in Gr.III and Gr.IV and a significant decrease in Gr.II. In respect with organic phosphorus, there were very high significant decrease in Gr.III, significant decrease in Gr.II and high significant decrease in Gr.IV

Clinical assessment of hepatic functional reserve using 99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases. Validation of the use of SPECT and a new indicator

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Onodera, Yuya; Tamaki, Nagara; Miyasaka, Kazuo; Takahashi, Kazuei; Sugai, Yukio; Togashi, Tadashi

2003-01-01

It is generally known that scintigraphy of 99m Tc diethylenetriamine pentaacetic acid-galactosyl human serum albumin ( 99m Tc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99m Tc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases. A liver phantom (a 50% concentration of 99m Tc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99m Tc-GSA was divided by a syringe SPECT of 99m Tc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99m Tc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects. The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r=0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild

Decrease in seroprevalence of Hepatitis A after the implementation of nationwide disposable tableware use in Taiwan

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Kan Wei-Chih

2010-11-01

Full Text Available Abstract Background Taiwan is an endemic area of viral hepatitis, including hepatitis A, which is transmitted mainly from the fecal-oral route. In order to reduce the transmission through food intake, the government implemented a policy of nationwide disposal tableware use in public eating places in 1982. We conducted a study to estimate the seroprevalence of Hepatitis A in a group of workers in Taiwan in 2005, determine the risk factors, and compare seroprevalence to published estimates in Taiwan to evaluate changes in the seroprevalence after the implementation of the nationwide disposal tableware use. Methods We recruited workers of an industrial park during their annual health examinations in 2005 and measured their anti-hepatitis A virus IgG titer using microparticle enzyme immunoassay. We compared the seroprevalence across different birth cohorts within the study population and also analyzed data from previous studies. Results The overall sero-positive rate was 22.0% in the 11,777 participants. The rate was much lower among those who were covered by the program since birth (born after 1982 in comparison with those who were not (2.7% vs. 25.3%, p Conclusions Data from both the current and previous studies in different time periods supported the effectiveness of disposal tableware in preventing the transmission of hepatitis A.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

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Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

2013-02-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

International Nuclear Information System (INIS)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

2013-01-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

Effects of urban stream burial on nitrogen uptake and ...

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Urbanization has resulted in extensive burial and channelization of headwater streams, yet little is known about impacts on stream ecosystem functions critical for reducing downstream nitrogen pollution. To characterize the biogeochemical impact of stream burial, we measured NO3- uptake, using 15N-NO3- isotope tracer releases, and whole stream metabolism, during four seasons in three paired buried and open streams reaches within the Baltimore Ecosystem Study Long-term Ecological Research Network. Stream burial increased NO3- uptake lengths, by a factor of 7.5 (p < 0.01) and decreased nitrate uptake velocity and areal nitrate uptake rate by factors of 8.2 (p = 0.01) and 9.6 (p < 0.001), respectively. Stream burial decreased gross primary productivity by a factor of 9.2 (p < 0.05) and decreased ecosystem respiration by a factor of 4.2 (p = 0.06). From statistical analysis of Excitation Emissions Matrices (EEMs), buried streams were also found to have significantly less labile dissolved organic matter. Furthermore, buried streams had significantly lower transient storage and water temperatures. Overall, differences in NO3- uptake and metabolism were primarily explained by decreased transient storage and light availability in buried streams. We estimate that stream burial increases daily watershed nitrate export by as much as 500% due to decreased in-stream retention and may considerably decrease carbon export via decreased primary production. These results

Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison.

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Lafferty, L; Treloar, C; Guthrie, J; Chambers, G M; Butler, T

2017-02-01

Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes. © 2016 John Wiley & Sons Ltd.

Decreased insulin secretory response of pancreatic islets during culture in the presence of low glucose is associated with diminished 45Ca2+ net uptake, NADPH/NADP+ and GSH/GSSG ratios

International Nuclear Information System (INIS)

Verspohl, E.J.; Kaiser, P.; Wahl, M.; Ammon, H.P.T.

1988-01-01

In isolated rat pancreatic islets maintained at a physiologic glucose concentration (5.6 mM) the effect of glucose on parameters which are known to be involved in the insulin secretion coupling such as NADPH, reduced glutathione (GSH), 86 Rb + efflux, and 45 Ca ++ net uptake were investigated. The insulinotropic effect of 16.7 mM glucose was decreased with the period of culturing during the first 14 days being significant after 2 days though in control experiments both protein content and ATP levels per islet were not affected and insulin content was only slightly decreased. Both NADPH and GSH decreased with time of culture. 86 Rb + efflux which is decreased by enhancing the glucose concentration from 3 to 5.6 mM in freshly isolated islets was not affected by culturing whatsoever, even not after 14 days of culture when there was not longer any insulin responsiveness to glucose. The 45 Ca ++ net uptake was decreased during culturing. The data indicate (1) that the diminished glucose-stimulated release of insulin during culturing is not due to cell loss or simple energy disturbances, (2) that more likely it is the result of a diminished 45 Ca ++ net uptake as a consequence of the inability of islet cells to maintain proper NADPH and GSH levels, and (3) that potassium ( 86 Rb + ) efflux may not be related to changes of NADPH and GSH

Measurement of hepatic volume and effective blood flow with radioactive colloids: Evaluation of development in liver diseases

International Nuclear Information System (INIS)

Fujii, M.; Uchino, H.; Kyoto Univ.

1982-01-01

Changes in hepatic volume and the blood flow effectively perfusing the liver parenchyma were studied as an assessment of the severity of liver diseases. Hepatic effective blood flow was estimated as the hepatic fractional clearance of radioactive colloids, obtained from the disappearance rate multiplied by the fraction of injected dose taken up by the liver. The hepatic fractional clearance was normal or not markedly decreased in patients with acute hepatitis which had developed favorably, but was severely decreased in patients with fulminant hepatitis. In liver diseases, the ratio of hepatic volume to fractional clearance was found to increase as the clearance decreased. In subjects with normal clearance, hepatic fractional clearance was correlated significantly with liver volume, indicating that hepatic effective blood flow is proportional to parenchymal volume in an unanesthetized, resting state. In biopsied cases changes in volume and blood flow accorded well with changes indicated by morphological criteria. In chronic persistent hepatitis, effective hepatic blood flow is not diminished. However, hepatic blood flow were observed between the cirrhosis or chronic aggressive hepatitis, and normal control groups. Extension of chronic inflammatory infiltration into the parenchyma distinguishes chronic aggressive hepatitis from chronic persistent hepatitis. Architecture is often disturbed in the former. These changes should be accompanied by disturbance of microcirculation. The present study indicates that the decrease in effective hepatic blood flow in chronic hepatitis and cirrhosis has two aspects: one is a summation of microcirculatory disturbances, and the other is a decrease in liver cell mass. (orig.)

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

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Oikawa, S; Oetzel, G R

2006-08-01

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections.

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Hayley Bennett

Full Text Available The prevalence of the hepatitis C virus (HCV remains high amongst people who inject drugs (PWID and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV.A dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality, with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR rates of 90-100% and increased uptake over varied horizons.SoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015-2027 ranged from 20-580 and 34-912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications, with a projected £5.4 million cost saving.While improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health

Aluminium alleviates manganese toxicity to rice by decreasing root symplastic Mn uptake and reducing availability to shoots of Mn stored in roots.

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Wang, Wei; Zhao, Xue Qiang; Hu, Zhen Min; Shao, Ji Feng; Che, Jing; Chen, Rong Fu; Dong, Xiao Ying; Shen, Ren Fang

2015-08-01

Manganese (Mn) and aluminium (Al) phytotoxicities occur mainly in acid soils. In some plant species, Al alleviates Mn toxicity, but the mechanisms underlying this effect are obscure. Rice (Oryza sativa) seedlings (11 d old) were grown in nutrient solution containing different concentrations of Mn(2+) and Al(3+) in short-term (24 h) and long-term (3 weeks) treatments. Measurements were taken of root symplastic sap, root Mn plaques, cell membrane electrical surface potential and Mn activity, root morphology and plant growth. In the 3-week treatment, addition of Al resulted in increased root and shoot dry weight for plants under toxic levels of Mn. This was associated with decreased Mn concentration in the shoots and increased Mn concentration in the roots. In the 24-h treatment, addition of Al resulted in decreased Mn accumulation in the root symplasts and in the shoots. This was attributed to higher cell membrane surface electrical potential and lower Mn(2+) activity at the cell membrane surface. The increased Mn accumulation in roots from the 3-week treatment was attributed to the formation of Mn plaques, which were probably related to the Al-induced increase in root aerenchyma. The results show that Al alleviated Mn toxicity in rice, and this could be attributed to decreased shoot Mn accumulation resulting from an Al-induced decrease in root symplastic Mn uptake. The decrease in root symplastic Mn uptake resulted from an Al-induced change in cell membrane potential. In addition, Al increased Mn plaques in the roots and changed the binding properties of the cell wall, resulting in accumulation of non-available Mn in roots. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

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Schiano, T D; Te, H S; Thomas, R M; Hussain, H; Bond, K; Black, M

2001-10-01

Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.

Radioiodine uptake by plants from soils

International Nuclear Information System (INIS)

Sabova, T.

1976-01-01

The uptake and accumulation of radioiodine by wheat, maize and peas from various types of soil have been studied. The uptake depends on the type of soil, on its content of organic matter and on the amount of fertilizer. Radioiodine is mainly accumulated in the roots. Accumulation in above-ground plant parts decreases in the following order: wheat, maize, peas. Uptake was highest from humus and clay soils and lowest from black and meadow soils. Application of chloride fertilizer or carrier iodine lead to an increase of radioiodine uptake in the whole plant. (author)

Dynamic Study on the Hepatobiliary Diseases with Combination of {sup 131}I-Rose bengal and {sup 198}Au-Colloid Scintiphotography

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Rhee, Yong Kok [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1971-03-15

The radioactive {sup 131}I-Rose bengal serial scintiphotography was performed in 62 patients with the hepatobiliary diseases and in 20 normal subjects. This approach permitted visualization of the hepatic uptake of {sup 131}I-Rose bengal from the circulation and its excretion into the biliary trees and the intestines. In some of these patients, gallbladder function was examined, using eggs as a gallbladder constrictor. The time of maximum hepatic uptake was well correlated to the conventional biochemical liver function tests. In addition to {sup 131}I-Rose bengal scintiphotography, {sup 198}Au-colloid scintiphotography was also performed to make comparison of these two tests. The results obtained were as follows: 1) In normal subjects, the maximum hepatic uptake of {sup 131}I-Rose bengal occurred at 23+-2.9 minutes, the initial hepatic excretion at 34+-5.1 minutes, the visualization of the gallbladder at 29+-5.7 minutes and the intestinal visualization at 54+-25.8 minutes. The radioactivity in the gallbladder decreased to 10.7+-5.0% one hour after the ingestion of eggs. 2) In the patients with cirrhosis of the liver, there was a delayed and decreased hepatic uptake. The maximum hepatic uptake occurred at 43+-12.9 minutes. The differences in the results of uptake between the cirrhotic and the normal group were statistically significant. The initial hepatic excretion occurred at 60+-18.5 minutes and had tendency of delaying compared with the normal controls. The gallbladder was visualized in 13 of 16 cases (81%) and its visualization occurred at 49+-14.6 minutes with a tendency to be delayed compared with the normal controls. The intestinal visualization occurred at 63+-15.8 minutes and its delaying tendency was somewhat more prominent. 3) In patients with hepatitis, the maximum hepatic uptake occurred at 59+-21.4 minutes and was significantly delayed. The initial hepatic excretion occurred at 82+-34.3 minutes and the results revealed a delaying tendency. The

Dynamic Study on the Hepatobiliary Diseases with Combination of 131I-Rose bengal and 198Au-Colloid Scintiphotography

International Nuclear Information System (INIS)

Rhee, Yong Kok

1971-01-01

The radioactive 131 I-Rose bengal serial scintiphotography was performed in 62 patients with the hepatobiliary diseases and in 20 normal subjects. This approach permitted visualization of the hepatic uptake of 131 I-Rose bengal from the circulation and its excretion into the biliary trees and the intestines. In some of these patients, gallbladder function was examined, using eggs as a gallbladder constrictor. The time of maximum hepatic uptake was well correlated to the conventional biochemical liver function tests. In addition to 131 I-Rose bengal scintiphotography, 198 Au-colloid scintiphotography was also performed to make comparison of these two tests. The results obtained were as follows: 1) In normal subjects, the maximum hepatic uptake of 131 I-Rose bengal occurred at 23±2.9 minutes, the initial hepatic excretion at 34±5.1 minutes, the visualization of the gallbladder at 29±5.7 minutes and the intestinal visualization at 54±25.8 minutes. The radioactivity in the gallbladder decreased to 10.7±5.0% one hour after the ingestion of eggs. 2) In the patients with cirrhosis of the liver, there was a delayed and decreased hepatic uptake. The maximum hepatic uptake occurred at 43±12.9 minutes. The differences in the results of uptake between the cirrhotic and the normal group were statistically significant. The initial hepatic excretion occurred at 60±18.5 minutes and had tendency of delaying compared with the normal controls. The gallbladder was visualized in 13 of 16 cases (81%) and its visualization occurred at 49±14.6 minutes with a tendency to be delayed compared with the normal controls. The intestinal visualization occurred at 63±15.8 minutes and its delaying tendency was somewhat more prominent. 3) In patients with hepatitis, the maximum hepatic uptake occurred at 59±21.4 minutes and was significantly delayed. The initial hepatic excretion occurred at 82±34.3 minutes and the results revealed a delaying tendency. The gallbladder was visualized in 15

Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity

DEFF Research Database (Denmark)

Henriksen, Jens Henrik; Ring-Larsen, H; Christensen, N J

1987-01-01

clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3...

Hepatic ABC transporters and triglyceride metabolism.

Science.gov (United States)

Parks, John S; Chung, Soonkyu; Shelness, Gregory S

2012-06-01

Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations. Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels. New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.

IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.

Science.gov (United States)

Shi, Huijie; Wang, Qingchun; Yang, Liu; Xie, Shouxia; Zhu, Haibo

2017-09-01

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2',3',5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) can eliminate hepatic steatosis in hamsters fed a high-fat diet (HFD), as a model of NAFLD. Compared with HFD-only controls, IMM-H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1 H-MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM-H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM-H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo , IMM-H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. Thus, IMM-H007 has therapeutic potential for NAFLD.

Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

Science.gov (United States)

Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

2017-03-01

Atmospheric CO 2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO 3 - ) or ammonium (NH 4 + ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO 2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO 2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO 3 - or NH 4 + as the N source. Elevated CO 2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO 2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO 2 plus warming, reduced NO 3 - -uptake rate per g root was correlated with a decrease in the concentration of NO 3 - -uptake proteins per g root, reduced NH 4 + uptake was correlated with decreased activity of NH 4 + -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO 2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

The 5th Canadian Symposium on Hepatitis C Virus: We Are Not Done Yet—Remaining Challenges in Hepatitis C

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Nicholas van Buuren

2016-01-01

Full Text Available Hepatitis C virus (HCV affects approximately 268,000 Canadians and results in more years of life lost than any other infectious disease in the country. Both the Canadian Institutes of Health Research (CIHR and the Public Health Agency of Canada (PHAC have identified HCV-related liver disease as a priority and supported the establishment of a National Hepatitis C Research Network. In 2015, the introduction of new interferon- (IFN- free therapies with high cure rates (>90% and few side effects revolutionized HCV therapy. However, a considerable proportion of the population remains undiagnosed and treatment uptake remains low in Canada due to financial, geographical, cultural, and social barriers. Comprehensive prevention strategies, including enhanced harm reduction, broader screening, widespread treatment, and vaccine development, are far from being realized. The theme of the 2016 symposium, “We’re not done yet: remaining challenges in Hepatitis C,” was focused on identifying strategies to enhance prevention, diagnosis, and treatment of HCV to reduce disease burden and ultimately eliminate HCV in Canada.

Hydrogen uptake by Azolla-Anabaena

International Nuclear Information System (INIS)

Ruschel, A.P.; Freitas, J.R. de; Silva, P.M.

1984-01-01

The hydrogen uptake in the Azolla-Anabaena system is studied. Tritium is used as tracer. Plants are incubated under different atmosphere composition: a) Air + 3 H 2 ; b) Air + CO 2 + 3 H 2 + CO; c) Air + 3 H 2 + CO; d) Air + CO 2 + 3 H 2 + CO to study the pathway of absorbed hydrogen in the Azolla - Anabaena system. Azolla-Anabaena showed greater hydrogen uptake under argonium atmosphere than under air. Carbon monoxide decreased hydrogen uptake. There are evidences of recycling of the hydrogen evolved through notrogenease. (Author) [pt

The Blood Disappearance Rate of 198Au-Colloid and Changes of Hepatic Blood Flow During Position Change in Normal Persons and in Patients with Various Hepatic Diseases

International Nuclear Information System (INIS)

Cho, Bo Yeon; Hong, Kee Suk; Koh, Chang Soon; Lee, Mun Ho

1977-01-01

To evaluate the diagnostic significance of the blood disappearance rate of 198 Au-colloid and to evaluate the change of hepatic blood flow during position change from supine to erect, we measured the half time of blood disappearance rate of 198 Au-colloid using external counting method in 94 normal persons and in 77 patients with various hepatic diseases. The results obtained were as follows: 1) In normal control, the mean blood disappearance half time of 198 Au-colloid in supine position was 2.7±0.4 minutes. There was no significant difference of hepatic blood flow in age and sex. 2) In acute hepatitis, chronic hepatitis and hepatic cirrhosis, the mean blood disappearance half times in supine position were 3.0±0.45, 3.5±0.74, 7.2±3.6 minutes respectively. The hepatic blood flow of the patients with chronic hepatitis and hepatic cirrhosis were significantly decreased than that of normal control. 3) In the normal control and acute hepatitis, the decreases of the hepatic blood flow during the position change from supine to erect were 27.7% and 22.6% respectively.

Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

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Lucia Natarelli

Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

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

Science.gov (United States)

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.

[Viral hepatitis A - possible diagnostic and therapeutic problems].

Science.gov (United States)

Husa, Petr; Husa, Petr

Viral hepatitis A (VHA) is the disease which has an ancient history. Reports of epidemic jaundice were described by Hippocrates in Greece during the 5th century B.C. Incidence of VHA in developed countries is dropping in last decades. What was once common disease is now very rare, usually emerging in local epidemies. With decreasing incidence of hepatitis A clinicians losing practical experiences with disease. Authors present possible diagnostic and therapeutic problems based on their experience with large epidemic of hepatitis A, which occurred in 2016-2017 in Brno area.Key words: hepatitis A (VHA) - hepatitis A virus (HAV).

Increase vs. decrease of calcium uptake by isolated heart cells induced by H2O2 vs. HOCl

International Nuclear Information System (INIS)

Kaminishi, T.; Matsuoka, T.; Yanagishita, T.; Kako, K.J.

1989-01-01

Adult rat heart myocytes were labeled rapidly with exogenous [45Ca2+]. Addition of 2.5 mM H2O2 to the heart cell suspension raised the content of rapidly exchangeable intracellular Ca2+ twofold, whereas addition of 1-30 mM HOCl decreased the Ca2+ content. The H2O2-induced increase in Ca2+ content was dependent on the medium Na+, pH, and temperature but was not significantly affected by addition of verapamil, diltiazem, amiloride, or 3-aminobenzamide. The [3H]ouabain binding to myocytes was suppressed by H2O2, whereas the Ca2+ efflux from myocytes was not influenced. An uncoupler, carbonyl cyanide m-chlorophenylhydrazone, reduced Ca2+ content, implying that the H2O2-induced change in Ca2+ content was not directly related to ATP depletion. On the other hand, the H2O2-induced Ca2+ accumulation in myocytes was prevented by deferoxamine or o-phenanthroline. These results suggest that H2O2 inhibited Na+-K+-ATPase, resulting in an increase in intracellular Na+ concentration and stimulation of sarcolemmal Na+-Ca2+ exchange activity, which caused a transient net Ca2+ influx into myocytes. By contrast, HOCl decreased the Ca2+ content of the rapidly exchangeable pool below control levels and this action of HOCl was antagonized by 1,4-dithiothreitol. HOCl accelerated Ca2+ efflux from myocytes. Ca2+ uptake and Ca2+-ATPase of the isolated sarcoplasmic reticular (SR) fraction were highly sensitive to the action of HOCl. Ca2+ uptake by intracellular sites, studied with myocytes permeabilized with digitonin, was inhibited by both H2O2 and HOCl. Thus these results suggest that HOCl inhibits the SR Ca2+ pump, resulting in the observed acceleration of Ca2+ efflux from and decline in Ca2+ content of myocytes

Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

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Young-il Kim

Full Text Available Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA, which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA, which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

Accretion of visceral fat and hepatic insulin resistance in pregnant rats.

Science.gov (United States)

Einstein, Francine H; Fishman, Sigal; Muzumdar, Radhika H; Yang, Xiao Man; Atzmon, Gil; Barzilai, Nir

2008-02-01

Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF-; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 +/- 0.3, Preg 10.0 +/- 1.0 g, P Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg.kg(-1).min(-1)) was highest in Nonpreg (19.4 +/- 2.0), lowest in Preg (11.1 +/- 1.4), and intermediate in PVF- (14.7 +/- 0.6; P insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 +/- 1.3, Preg 9.3 +/- 0.5 mg.kg(-1).min(-1); P insulin sensitivity was similar to nonpregnant levels in PVF- (HGP 4.9 +/- 0.8 mg.kg(-1).min(-1)). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 +/- 0.4 vs. Preg 3.2 +/- 0.3 mg/g) and decreased with removal of VF (PVF- 1.3 +/- 0.4 mg/g; P insulin action in pregnancy.

Effects of hepatic ischemia-reperfusion injury on the P-glycoprotein activity at the liver canalicular membrane and blood-brain barrier determined by in vivo administration of rhodamine 123 in rats.

Science.gov (United States)

Miah, Mohammad K; Shaik, Imam H; Bickel, Ulrich; Mehvar, Reza

2014-04-01

To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker. Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis. P-gp protein levels at the liver canalicular membrane were increased by twofold after 24 h of reperfusion. However, the biliary excretion of RH-123 was reduced in these rats by 26%, presumably due to IR-induced reductions in the liver uptake of the marker and hepatic ATP concentrations. At the BBB, a 24% overexpression of P-gp in the 24-h IR animals was associated with a 30% decrease in the apparent brain uptake clearance of RH-123. The pharmacokinetics or brain distribution of RH-123 was not affected by the 12-h IR injury. Hepatic IR injury may alter the peripheral pharmacokinetics and brain distribution of drugs that are transported by P-gp and possibly other transporters.

Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV.

Science.gov (United States)

Deterding, Katja; Tegtmeyer, Björn; Cornberg, Markus; Hadem, Johannes; Potthoff, Andrej; Böker, Klaus H W; Tillmann, Hans L; Manns, Michael P; Wedemeyer, Heiner

2006-12-01

The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.

CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

Directory of Open Access Journals (Sweden)

Yuan Liu

2013-12-01

Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

Viral hepatitis vaccination during pregnancy.

Science.gov (United States)

Zhao, Yueyuan; Jin, Hui; Zhang, Xuefeng; Wang, Bei; Liu, Pei

2016-04-02

Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy.

Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

Science.gov (United States)

The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid tran...

Hepatic Arterial Perfusion Scintigraphy with '99mTc-Macroaggregated Albumin in Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Kim, Gang Deuk; Sohn, Kwang Joon; Min, Kyung Yoon; Kwon, Young Mi; Kim, Chang Guhn; Noh, Byung Suk; Won, Jong Jin

1994-01-01

Hepatic arterial perfusion scintigraphy with '9 9m Tc macroggregated albumin (HAPS) study was carried out in 16 patients with hepatocellular carcinoma (HCC) and in six patients without liver tumor to evaluate HAPS findings of hepatocellular carcinoma and use fullness of HAPS. HAPS with planar and SPECT study were performed in 22 patients after conventional hepatic or celiac arteriography. For HAPS study, 4 5 mCi of MAA mixed with 2 ml of saline was injected into proper hepatic artery or its distal branches at the rate of approximately 1 ml/sec. We analysed 21 HCCs over 2 cm in diameter(average diameter: 6.4 cm) and 17 of 21 HCCs were over 4 cm in diameter. CT, sonography and angiography were performed within two week in all 16 patients and liver scan was performed in 12 patients. Three different pattern of tumor perfusion were observed in 16 patients with HCC. 1) diffuse increased perfusion in 16 of 21(76%) 2) increased peripheral perfusion in 4 of 21(19%) 3) diffuse decreased perfusion in 1 of 21 (5%) Arteriovenous shunt indicated by lung uptake of MAA were observed in 9 of 16 (56% ). In contrast, angiography demonstrates arteriovenous shunt in 2 of 16 (13%). There was no accumulation of radioactivity on RRC blood pool scan in all six patients with HCC examined. HAPS is useful study in evaluation of perfusion pattern or vascularity of HCC and in detection of arteriovenous shunt.

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium.

Science.gov (United States)

Huang, Jian; Zhao, Lei; Yang, Ping; Chen, Zhen; Ruan, Xiong Z; Huang, Ailong; Tang, Ni; Chen, Yaxi

2017-09-15

Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS. We recently found that CD36 overexpression enhanced HBV replication. In this study, we further explored the mechanism by which CD36 overexpression promotes HBV replication. Our data showed that CD36 overexpression increased HBV replication, and CD36 knockdown inhibited HBV replication. RNA sequencing found some of the differentially expressed genes were involved in calcium ion homeostasis. CD36 overexpression elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic calcium level. Calcium chelator BAPTA-AM could override the HBV replication increased by CD36 overexpression, and the calcium activator thapsigargin could improve the HBV replication reduced by CD36 knockdown. We further found that CD36 overexpression activated Src kinase, which plays an important role in the regulation of the store-operated Ca 2+ channel. An inhibitor of Src kinase (SU6656) significantly reduced the CD36-induced HBV replication. We identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. CD36 may represent a potential therapeutic target for the treatment of CHB patients with MS. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats.

Science.gov (United States)

Arpacı, Hande; Çomu, Faruk Metin; Küçük, Ayşegül; Kösem, Bahadır; Kartal, Seyfi; Şıvgın, Volkan; Turgut, Hüseyin Cihad; Aydın, Muhammed Enes; Koç, Derya Sebile; Arslan, Mustafa

2016-01-01

Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.

Modeling the Health and Economic Burden of Hepatitis C Virus in Switzerland.

Science.gov (United States)

Müllhaupt, Beat; Bruggmann, Philip; Bihl, Florian; Blach, Sarah; Lavanchy, Daniel; Razavi, Homie; Semela, David; Negro, Francesco

2015-01-01

Chronic hepatitis C virus infection is a major cause of liver disease in Switzerland and carries a significant cost burden. Currently, only conservative strategies are in place to mitigate the burden of hepatitis C in Switzerland. This study expands on previously described modeling efforts to explore the impact of: no treatment, and treatment to reduce HCC and mortality. Furthermore, the costs associated with untreated HCV were modeled. Hepatitis C disease progression and mortality were modeled. Baseline historical assumptions were collected from the literature and expert interviews and strategies were developed to show the impact of different levels of intervention (improved drug cure rates, treatment and diagnosis) until 2030. Under the historical standard of care, the number of advanced stage cases was projected to increase until 2030, at which point the annual economic burden of untreated viremic infections was projected to reach €96.8 (95% Uncertainty Interval: €36 - €232) million. Scenarios to reduce HCV liver-related mortality by 90% by 2030 required treatment of 4,190 ≥F2 or 3,200 ≥F3 patients annually by 2018 using antivirals with a 95% efficacy rate. Delaying the implementation of these scenarios by 2 or 5 years reduced the impact on mortality to 75% and 57%, respectively. With today's treatment efficacy and uptake rates, hepatitis C disease burden is expected to increase through 2030. A substantial reduction in disease burden can be achieved by means of both higher efficacy drugs and increased treatment uptake. However, these efforts cannot be undertaken without a simultaneous effort to diagnose more infections.

Central effects of humanin on hepatic triglyceride secretion.

Science.gov (United States)

Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H

2015-08-01

Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. Copyright © 2015 the American Physiological Society.

Hepatitis C virus treatment rates and outcomes in HIV/hepatitis C virus co-infected individuals at an urban HIV clinic.

Science.gov (United States)

Murray, Melanie C M; Barrios, Rolando; Zhang, Wendy; Hull, Mark; Montessori, Valentina; Hogg, Robert S; Montaner, Julio S G

2011-01-01

The factors associated with hepatitis C virus (HCV) treatment uptake and responses were assessed among HCV/HIV co-infected individuals referred for HCV therapy at an urban HIV clinic. Retrospective review of HIV/HCV patients enrolled in the HCV treatment program at the John Ruedy Immunodeficiency Clinic in Vancouver. The factors associated with treatment uptake were assessed using multivariate analysis. A total of 134 HCV/HIV co-infected individuals were recalled for assessment for HCV therapy. Overall 64 (48%) initiated treatment, and of those treated 49 (76.6%) attained end treatment response, whereas 35 (57.8%) achieved sustained virological response (SVR). When evaluated by genotype, 53% (17/32) of those with genotype 1, and 65% (20/31) of those with genotype 2 or 3 infections attained SVR. In treated individuals, alanine aminotransferase dropped significantly after treatment (P<0.001). During treatment, CD4 counts dropped significantly (P<0.001) in all patients. The counts recovered to baseline in patients who achieved SVR, but remained lower in patients who failed the therapy (P=0.015). On multivariate analysis, history of injection drug use (odds ratio: 3.48; 95% confidence interval: 1.37-8.79; P=0.009) and low hemoglobin levels (odds ratio: 4.23; 95% confidence interval: 1.36-13.10; P=0.013) were associated with those who did not enter the treatment. Only half of treatment-eligible co-infected patients referred for the therapy initiated treatment. Of those referred for the therapy, history of injection drug use was associated with lower rates of treatment uptake. Treated HIV/HCV co-infected individuals benefitted from both decreased alanine aminotransferase (independent of SVR), and rates of SVR similar to those described in HCV monoinfected patients.

Prevention of hepatitis B

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Marta Estera Kowalska

2017-07-01

Full Text Available Hepatitis B (Hepatitis B is a hepatitis B virus (HBV -based liver disease. This virus has an affinity for liver cells, it can cause both acute and chronic viral infections of varying severity. The consequences of chronic HBV infection can be cirrhosis and liver cancer. In Poland in 1989 a preventive program was implemented to reduce HBV infection. Universal vaccinations have been introduced to reduce the prevalence of Type B hepatitis B from 40.3 / 100,000 in 1989 to 7/100 in 2000. In the last 20 years in Poland there has been huge progress in the prevention and suppression of HBV infections. Decrease in the incidence of hepatitis B is mainly the result of the introduction of compulsory vaccination and improving hygiene procedures and improve sanitation aimed at aborting the pathways of the virus. However, still a large part of society is not immune on HBV infection acting potential group of the risk of infection. In addition, in the era of a growing group of followers. movements of the anti vaccine it is necessary to continue to promote knowledge of HBV and the efficacy and safety of vaccination.

Studies on the clinical course of chronic hepatitis in the patients who underwent serial needle liver biopsies

International Nuclear Information System (INIS)

Hirata, Tetsuro

1984-01-01

In order to evaluate the changes in biochemical liver function tests and hepatic scintigraphic findings of chronic hepatitis, the author analyzed 35 patients who underwent serial liver biopsies. The results were summerized as follows: 1. Histological deteriorations in chronic hepatitis more inclined to be presented in the scintigraphic abnormalities such as the increased uptake of radioisotope in the spleen and bone marrow than the deteriorations in biochemical liver function tests. Moreover, the increased radioisotope uptake by spleen and bone marrow in hepatic scintigram highly correlated with histological deteriorations. On the other hand, in the cases with histological improvement no scintigraphic improvement was ovserved. 2. Comparing the changes in the result of liver function tests with histological features, biochemical deteriorations significantly correlated with histological deteriorations, although biochemical improvements were not reliable indicators of histological improvements. 3. Changes in biochemical parameters such as serum GOT, GPT, albumin, γ-globulin, TTT and ALP were analyzed by means of Hayashi's second method of quantification and predictive values for histological feactures were calculated. As a result, histological deteriorations were predicted in 89.5% of the cases, but histological improvements were predicted only in 66.7%. In the various biochemical parameters, γ-globulin was considered as most important in predicting histological features and ALP was ranked the second. (J.P.N.)

Hepatic uptake of radioiodine in patients with thyroid cancer: the good, the bad and the aesthetically impaired

International Nuclear Information System (INIS)

Roman, M.; Larcos, G.; Gruenewald, S.; Devadas, M.; Boyages, S.

2002-01-01

Full text: There is debate over the prognostic significance of diffuse hepatic uptake (DHU) of radioiodine in patients with thyroid cancer (DTC). Accordingly we compared outcome in DTC patients with and without DHU and no abnormality on their radioiodine scan. We reviewed 408 studies in 198 patients who underwent radioiodine scanning (treatment or surveillance) for DTC over a five-year period. Of these 234 (57%) showed DHU; 100/408 showed no evidence of functioning thyroid tissue. These were 22 high dose I 131 treatments, 48 I 131 and 30 I 123 surveillance scans in 72 patients (54 women, 18 men, age: 43( 14 years; tumour type: 88% papillary, 10% follicular, 2% other; mean follow-up 12.2 (11.1 months). Outcome was assessed by clinical, pathological (thyroglobulin or histopathology) and/or radioiodine scanning. Of the 100 scans there were 17 (17%) that had DHU (group A) and 83 (83%) that were negative (group B). In group A, eight of 17 (47%) had or developed residual functioning thyroid tissue or DTC versus 29 of 83 (35%) in group B (p=ns). The only factor associated with DHU was high dose I 131 (p<0.001) but not the gender, age or type of cancer. We conclude that (a) DHU is common in patients with DTC; (b) if there is otherwise physiological distribution of radioiodine, DHU does not indicate an adverse short term outcome in DTC patients. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

DEFF Research Database (Denmark)

Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

2002-01-01

-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver...... with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat...... 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO...

Treatment with radioisotopes (RI), (40). A discussion of a morphological diagnosis and a diagnosis of cell function in the liver with sup(99m)Tc-HIDA (sup(99m)Tc-PI) and sup(99m)Tc-phytate

Energy Technology Data Exchange (ETDEWEB)

Asahara, A [Central Hospital of JNR, Tokyo (Japan)

1978-11-01

sup(99m)Tc-N-N-(N'(2,6 dimethylphenyl) carbamoyl methyl) iminodiacetic acid (sup(99m)Tc-HIDA) or sup(99m)Tc-phytate was administered to the same case, and their uptake into the liver was discussed by hepatic scintigraphy and hepatogram. As a result, hepatic images of subjects with normal liver function and those with cholelithiasis whose biliary flow was normal were the same, and there was no difference in a morphological diagnosis between them. Sufficient images could not be obtained because sup(99m)Tc-HIDA uptake into the liver decreased in acute hepatitis and acute obstructive jaundice, but sufficient images could be obtained by using sup(99m)Tc-phytate and its uptake into the liver was normal. The uptake of both agents decreased in most of the subjects with liver cirrhosis. As a collective result of both agents, various specific patterns of their uptake were showed according to diseases. sup(99m)Tc-phytate is more useful when an examination is made only to take hepatic image, because this agent is less limit for hepatic imaging. Uptake of sup(99m)Tc-HIDA and sup(99m)Tc-phytate into the liver and their excretion were almost the same in most of diseases, and there was no difference in diagnostic application merits between them. Excretion rate of sup(99m)Tc-HIDA was very low in Dubin-Johnson syndrome, but that of sup(99m)Tc-pyridoxylidene isoleusin (PI) was almost normal. It was supposed that metabolism of sup(99m)Tc-HIDA in hepatic cells differs from that of sup(99m)Tc-PI. (Tsunoda, M.).

Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

Science.gov (United States)

Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

2016-01-01

In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

Hepatic Complications of Anorexia Nervosa.

Science.gov (United States)

Rosen, Elissa; Bakshi, Neeru; Watters, Ashlie; Rosen, Hugo R; Mehler, Philip S

2017-11-01

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.

Meal-induced changes in splanchnic blood flow and oxygen uptake in middle-aged healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Søndergaard, SB; Møller, Søren

2006-01-01

OBJECTIVE: For decades, the determination of changes in splanchnic blood flow and oxygen uptake after a meal has been used in the management of patients with suspected chronic intestinal ischaemia. However, little is known about the normal meal-induced responses. The aim of the present study...... was therefore to measure the splanchnic blood flow and oxygen uptake before and after a standardized meal in a group of middle-aged normal volunteers. MATERIAL AND METHODS: Splanchnic blood flow and oxygen uptake were determined at baseline and after a 3600-kJ mixed meal in 8 healthy women (50-70 years) and 10...... healthy men (52-76 years). Splanchnic blood flow was measured during hepatic vein catheterization by indirect Fick principle with indocyanine green as the indicator. Splanchnic oxygen uptake was calculated from splanchnic blood flow and the arteriovenous oxygen difference. RESULTS: The meal induced...

The 3rd Canadian Symposium on Hepatitis C Virus: Expanding Care in the Interferon-Free Era

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Sonya A MacParland

2014-01-01

Full Text Available Hepatitis C virus (HCV currently infects approximately 250,000 individuals in Canada and causes more years of life lost than any other infectious disease in the country. In August 2011, new therapies were approved by Health Canada that have achieved higher response rates among those treated, but are poorly tolerated. By 2014/2015, short-course, well-tolerated treatments with cure rates >95% will be available. However, treatment uptake is poor due to structural, financial, geographical, cultural and social barriers. As such, ‘Barriers to access to HCV care in Canada’ is a crucial topic that must be addressed to decrease HCV disease burden and potentially eliminate HCV in Canada. Understanding how to better care for HCV-infected individuals requires integration across multiple disciplines including researchers, clinical services and policy makers to address the major populations affected by HCV including people who inject drugs, baby boomers, immigrants and Aboriginal and/or First Nations people. In 2012, the National CIHR Research Training Program in Hepatitis C organized the 1st Canadian Symposium on Hepatitis C Virus (CSHCV in Montreal, Quebec. The 2nd CSHCV was held in 2013 in Victoria, British Columbia. Both symposia were highly successful, attracting leading international faculty with excellent attendance leading to dialogue and knowledge translation among attendees of diverse backgrounds. The current article summarizes the 3rd CSHCV, held February 2014, in Toronto, Ontario.

SEIR model simulation for Hepatitis B

Science.gov (United States)

Side, Syafruddin; Irwan, Mulbar, Usman; Sanusi, Wahidah

2017-09-01

Mathematical modelling and simulation for Hepatitis B discuss in this paper. Population devided by four variables, namely: Susceptible, Exposed, Infected and Recovered (SEIR). Several factors affect the population in this model is vaccination, immigration and emigration that occurred in the population. SEIR Model obtained Ordinary Differential Equation (ODE) non-linear System 4-D which then reduces to 3-D. SEIR model simulation undertaken to predict the number of Hepatitis B cases. The results of the simulation indicates the number of Hepatitis B cases will increase and then decrease for several months. The result of simulation using the number of case in Makassar also found the basic reproduction number less than one, that means, Makassar city is not an endemic area of Hepatitis B.

Epidemiology of hepatitis B and hepatitis C in Lebanon.

Science.gov (United States)

Abou Rached, Antoine; Abou Kheir, Selim; Saba, Jowana; Ammar, Walid

2016-03-01

Hepatitis B and C are two potentially life threatening liver infections. Lebanon is ranked as a zone of moderate endemicity. This study aimed to determine the prevalence of hepatitis B and C in Lebanon and their distribution according to age, region and sex. This national prospective cross-sectional study was conducted from January 2011 till December 2012 in the six Lebanese Governorates in collaboration with municipalities, the Ministry of Public Health, Health Centres and dispensaries. An upcoming screening for hepatitis B and C was announced? in different districts of each Governorate. All individuals presenting to local laboratory, not known to have chronic hepatitis, were asked for a blood sample and answered a questionnaire addressing sex, age, place of birth and residence. Screening tests were "Abbots" for hepatitis B and "Human Hexagon" for hepatitis C. PCR testing was used to confirm the positivity of the previous tests. Of 31147 individuals screened, 542 had a rapid test positive for HBV (prevalence 1.74%, 95% CI 1.6-1.89) with a male to female ratio of 1.08. This prevalence was higher in the South and Nabatieh (1.9%) compared to Beirut (0.73%). Of 31,147 individuals screened, 64 had a rapid test positive for HCV (prevalence 0.21%, 95% CI 0.16-0.27) with a male to female ratio of 0.85. This prevalence was higher in Nabatieh (0.61%) compared to Mount Lebanon (0.08%). The prevalence of HBV and HCV in Lebanon is 1.74% and 0.21%, respectively with a higher prevalence in South and Nabatieh districts. These data rank Lebanon amongst countries with low endemicity for both viruses. Decrease in the prevalence of HBV is due to awareness campaign as well as success of the MOPH National Hepatitis Program in vaccinating all new born since 1998 and in screening and vaccinating high risk groups. Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

OpenAIRE

Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime

2013-01-01

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA le...

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

Directory of Open Access Journals (Sweden)

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.

Use of HOMA-IR in hepatitis C.

Science.gov (United States)

Eslam, M; Kawaguchi, T; Del Campo, J A; Sata, M; Khattab, M Abo-Elneen; Romero-Gomez, M

2011-10-01

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent manner and contributes to steatosis, progression of fibrosis and resistance to interferon plus ribavirin therapy. Our understanding of HCV-induced IR has improved considerably over the years, but certain aspects concerning its evaluation still remain elusive to clinical researchers. One of the most important issues is elucidating the ideal method for assessment of IR in the setting of hepatitis C. The hyperinsulinaemic euglycaemic clamp is the gold standard method for determining insulin sensitivity, but is impractical as it is labour intensive and time-consuming. To date, all human studies except for four where IR was evaluated in the HCV setting, an estimation of IR has been used rather than direct measurements of insulin-mediated glucose uptake. The most commonly used estimation in the HCV population is the homeostasis model assessment of insulin resistance (HOMA-IR) which is calculated from a single measurement of fasting insulin and glucose. In this article, we review the use and reporting of HOMA in the literature and provide guidance on its appropriate as well as inappropriate use in the hepatitis setting. © 2011 Blackwell Publishing Ltd.

Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake

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Angela Oliveira Pisco

2014-10-01

Full Text Available Expression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC transporters expression, preventing further accumulation of drugs. However, we found that decreased accumulation of drugs and fluorescent dyes was also contributed by a reduced uptake by the resistant cells. Confocal time-lapse microscopy and flow cytometry revealed that fluid-phase endocytosis was diminished in drug-resistant cells compared to drug-sensitive cells. Drug uptake was increased by insulin co-treatment when cells were grown in methylcellulose and monitored under the microscope, but not when cultured in suspension. We propose that multi-drug resistance is not solely achieved by enhanced efflux capacity but also by supressed intake of the drug offering an alternative target to overcome drug resistance or potentiate chemotherapy.

The Blood Disappearance Rate of 1{sup 98A}u-Colloid and Changes of Hepatic Blood Flow During Position Change in Normal Persons and in Patients with Various Hepatic Diseases

Energy Technology Data Exchange (ETDEWEB)

Cho, Bo Yeon [Capital Armed Force General Hospital, Seoul (Korea, Republic of); Hong, Kee Suk; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1977-03-15

To evaluate the diagnostic significance of the blood disappearance rate of {sup 198}Au-colloid and to evaluate the change of hepatic blood flow during position change from supine to erect, we measured the half time of blood disappearance rate of {sup 198}Au-colloid using external counting method in 94 normal persons and in 77 patients with various hepatic diseases. The results obtained were as follows: 1) In normal control, the mean blood disappearance half time of {sup 198}Au-colloid in supine position was 2.7+-0.4 minutes. There was no significant difference of hepatic blood flow in age and sex. 2) In acute hepatitis, chronic hepatitis and hepatic cirrhosis, the mean blood disappearance half times in supine position were 3.0+-0.45, 3.5+-0.74, 7.2+-3.6 minutes respectively. The hepatic blood flow of the patients with chronic hepatitis and hepatic cirrhosis were significantly decreased than that of normal control. 3) In the normal control and acute hepatitis, the decreases of the hepatic blood flow during the position change from supine to erect were 27.7% and 22.6% respectively.

Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

Energy Technology Data Exchange (ETDEWEB)

Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

1985-07-01

The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

Kinetics of zinc uptake and exchange by primary cultures of rat hepatocytes

International Nuclear Information System (INIS)

Pattison, S.E.; Cousins, R.J.

1986-01-01

The kinetics of 65 Zn 2+ uptake and exchange by hepatocytes in primary culture have been examined in detail to provide a basis for analyzing hormonal regulation of hepatic zinc metabolism. 65 Zn 2+ uptake was found to be a biphasic process. The slow phase represents an exchange between Zn 2+ in the medium and preexisting, intracellular zinc pools. This exchange rate was saturable with a medium zinc concentration of 9.5 microM eliciting one-half the maximum exchange rate and a maximum exchange rate of 9.9 pmol Zn 2+ . min-1 . mg protein-1 in the presence of bovine serum albumin. In the absence of albumin, a secondary, nonsaturable uptake rate was observed. The slow phase was relatively selective, and of the divalent transition metal ions tested, only Cd 2+ and Mn 2+ caused inhibition. The rate of exchange suggests total hepatocyte zinc has a turnover rate of approximately 30 h. The fast phase of 65 Zn 2+ reflects net Zn 2+ accumulation into a labile pool. The initial rates for this process were too fast to be measured accurately, but steady-state measurements allowed determination of the labile pool size. The pool dimensions saturated in the presence [Kapp = 28.6 microM; pool capacity = 0.44 nmol Zn 2+ /mg protein] and absence [Kapp = 11.8 microM; pool capacity = 0.34 nmol Zn 2+ /mg protein] of bovine serum albumin. Kinetics and equilibria of Zn 2+ uptake into the labile pool suggest that the latter acts as a source of Zn 2+ for the slow-exchange phase. Dexamethasone stimulated slow Zn 2+ exchange and also increased the labile pool size. The data suggest physiological factors alter hepatic zinc metabolism by influencing both intracellular Zn 2+ pools

Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

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Norio Yokoigawa

2009-04-01

Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

Uptake and transport of chromium in plants

International Nuclear Information System (INIS)

Ramachandran, V.; D'souza, T.J.; Mistry, K.B.

1980-01-01

The uptake of chromium, an important soil and water pollutant, by five different plant species was examined in nutrient culture experiments using chromium-51 as a tracer. The concentration in aerial tissues of both trivalent and hexavalent forms of chromium was the greatest in peas followed by beans, tomato and the cereals over identical uptake periods. The uptake of 51 Cr 3+ was, in general, greater than 51 CrO 4 2- . Studies with bean plants indicated that shoot uptake of both forms of chromium decreased with increasing pH and salt concentration of the external solution. Concentrations of 10 -4 M and 10 -5 M DNP inhibited 51 Cr uptake by bean shoots. (author)

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

International Nuclear Information System (INIS)

Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

2013-01-01

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

Energy Technology Data Exchange (ETDEWEB)

Cao Wei, E-mail: cawe-001@163.com [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Li Jing, E-mail: lijing02@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Burn and Plastic Surgery (China); Wu Zhiqun, E-mail: zhiqunwu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Zhou Changxi, E-mail: changxizhou@163.com [Chinese PLA General Hospital, Department of Respiratory Disease (China); Liu Xi, E-mail: xiliu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China); Wan Yi, E-mail: yiwan@163.com [The Fourth Military Medical University, Department of Health Statistics, Institute for Health Informatics (China); Duan Yunyou, E-mail: yunyouduan@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China)

2013-06-15

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Ozone uptake, water loss and carbon exchange dynamics in annually drought-stressed Pinus ponderosa forests: measured trends and parameters for uptake modeling.

Science.gov (United States)

Panek, Jeanne A

2004-03-01

This paper describes 3 years of physiological measurements on ponderosa pine (Pinus ponderosa Dougl. ex Laws.) growing along an ozone concentration gradient in the Sierra Nevada, California, including variables necessary to parameterize, validate and modify photosynthesis and stomatal conductance algorithms used to estimate ozone uptake. At all sites, gas exchange was under tight stomatal control during the growing season. Stomatal conductance was strongly correlated with leaf water potential (R2=0.82), which decreased over the growing season with decreasing soil water content (R2=0.60). Ozone uptake, carbon uptake, and transpirational water loss closely followed the dynamics of stomatal conductance. Peak ozone and CO2 uptake occurred in early summer and declined progressively thereafter. As a result, periods of maximum ozone uptake did not correspond to periods of peak ozone concentration, underscoring the inappropriateness of using current metrics based on concentration (e.g., SUM0, W126 and AOT40) for assessing ozone exposure risk to plants in this climate region. Both Jmax (maximum CO2-saturated photosynthetic rate, limited by electron transport) and Vcmax (maximum rate of Rubisco-limited carboxylation) increased toward the middle of the growing season, then decreased in September. Intrinsic water-use efficiency rose with increasing drought stress, as expected. The ratio of Jmax to Vcmax was similar to literature values of 2.0. Nighttime respiration followed a Q10 of 2.0, but was significantly higher at the high-ozone site. Respiration rates decreased by the end of the summer as a result of decreased metabolic activity and carbon stores.

Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

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Chuan Wang

Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

International Nuclear Information System (INIS)

Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan; Kim, Hyung Sik; Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung; Oh, Seon-Hee; Jun, Dae Won; Lee, Byung-Hoon

2017-01-01

Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

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Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyung Sik [School of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Oh, Seon-Hee [The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Jun, Dae Won [Internal Medicine, Hanyang University School of Medicine, Seoul 133-791 (Korea, Republic of); Lee, Byung-Hoon, E-mail: lee@snu.ac.kr [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of)

2017-02-01

Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

OpenAIRE

Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

2016-01-01

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal bu...

β-Carotene-9′,10′-Oxygenase Status Modulates the Impact of Dietary Tomato and Lycopene on Hepatic Nuclear Receptor–, Stress-, and Metabolism-Related Gene Expression in Mice123

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Tan, Hsueh-Li; Moran, Nancy E.; Cichon, Morgan J.; Riedl, Ken M.; Schwartz, Steven J.; Erdman, John W.; Pearl, Dennis K.; Thomas-Ahner, Jennifer M.; Clinton, Steven K.

2014-01-01

Tomato and lycopene (ψ, ψ-carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with β-carotene-9′,10′-monooxygenase (Bco2) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2−/− mice (3-wk-old; n = 36) were fed semi-purified control, 10% tomato powder–containing, or 0.25% lycopene beadlet–containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2−/− mice compared with WT (P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apolipoprotein (apo)-6′-, apo-8′-, and apo-12′-lycopenal concentrations. Hepatic expression of β-carotene-15,15’-monooxygenase was increased in Bco2−/− mice compared with WT (P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes (≥1.5-fold, P lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor-α, histone deacetylase 3, nuclear receptor coactivator 4, RevErbA-β, glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ, coactivator 1 β was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid

Carbon tetrachloride treatment induces anorexia independently of hepatitis in rats.

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Okamoto, T; Okabe, S

2000-08-01

Oxidative stress is involved in the development of anorexia. In the present study, we examined the possible involvement of anorexia in oxygen radical-induced hepatitis. A low dose of carbon tetrachloride (1 ml/kg of a 1:1 solution with olive oil) was orally administered to rats with and without food restriction. In rats with food restriction, carbon tetrachloride treatment induced hepatitis and reduced the body weight gain. In contrast, carbon tetrachloride treatment did not induce hepatitis in rats without food restriction, but the body weight was decreased. In these rats, the loss of body weight was accompanied by a decrease in food intake. The present results indicate that the administration of a low dose of carbon tetrachloride to rats without food restriction induced anorexia independently of hepatitis.

Silicate reduces cadmium uptake into cells of wheat

International Nuclear Information System (INIS)

Greger, Maria; Kabir, Ahmad H.; Landberg, Tommy; Maity, Pooja J.; Lindberg, Sylvia

2016-01-01

Cadmium (Cd) is a health threat all over the world and high Cd content in wheat causes high Cd intake. Silicon (Si) decreases cadmium content in wheat grains and shoot. This work investigates whether and how silicate (Si) influences cadmium (Cd) uptake at the cellular level in wheat. Wheat seedlings were grown in the presence or absence of Si with or without Cd. Cadmium, Si, and iron (Fe) accumulation in roots and shoots was analysed. Leaf protoplasts from plants grown without Cd were investigated for Cd uptake in the presence or absence of Si using the fluorescent dye, Leadmium Green AM. Roots and shoots of plants subjected to all four treatments were investigated regarding the expression of genes involved in the Cd uptake across the plasma membrane (i.e. LCT1) and efflux of Cd into apoplasm or vacuole from the cytosol (i.e. HMA2). In addition, phytochelatin (PC) content and PC gene (PCS1) expression were analysed. Expression of iron and metal transporter genes (IRT1 and NRAMP1) were also analysed. Results indicated that Si reduced Cd accumulation in plants, especially in shoot. Si reduced Cd transport into the cytoplasm when Si was added both directly during the uptake measurements and to the growth medium. Silicate downregulated LCT1 and HMA2 and upregulated PCS1. In addition, Si enhanced PC formation when Cd was present. The IRT1 gene, which was downregulated by Cd was upregulated by Si in root and shoot facilitating Fe transport in wheat. NRAMP1 was similarly expressed, though the effect was limited to roots. This work is the first to show how Si influences Cd uptake on the cellular level. - Highlights: • Si decreases accumulation and translocation of Cd in plants at tissue level. • This work is the first to show how Si influences Cd uptake. • Si decreases Cd uptake into cell and downregulates heavy metal transporter LCT1. • Si downregulates HMA2 transporter, which regulates Cd transport from root to shoot. • Si increases phytochelatin formation

Relationship between the murine Ah locus and 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatic metabolism, enzyme induction, and toxicity

International Nuclear Information System (INIS)

Shen, E.S.

1988-01-01

The influence of the Ah locus and hepatic microsomal enzyme induction on 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) metabolism and hepatotoxicity was investigated using C57BL/6J (C57) and DBA/2J (DBA) mice. C57 mice are more sensitive to toxic and enzyme inductive effects of 2,3,7,8-TCDD than DBA mice. Characterization of interstrain differences in hepatic enzyme induction, 2,3,7,8-TCDD metabolism, and hepatotoxicity may aid in identifying the mechanism(s) of 2,3,7,8-TCDD toxicity. The hepatic uptake and metabolism of [ 14 C]2,3,7,8-TCDD were studied using isolated hepatocytes from control and 2,3,7,8-TCDD-pretreated C57 and DBA mice. Pretreated mice were injected with 2,3,7,8-TCDD at doses that maximally induce aryl hydrocarbon hydroxylase activity or at doses that approach the LD 50 value. Despite the induction of hepatic 7-ethoxyresorufin O-deethylase activity and benzo[a]pyrene metabolism, all 2,3,7,8-TCDD pretreatment doses failed to increase the rate of [ 14 C]2,3,7,8-TCDD metabolism for both C57 and DBA mice. These results suggest that the uptake and rate of hepatic metabolism of 2,3,7,8-TCDD do not correlate with genetic differences at the murine Ah locus

Hepatic diseases related to triglyceride metabolism.

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Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

2013-10-01

Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

Clofibrate improves glucose tolerance in fat-fed rats but decreases hepatic glucose consumption capacity

NARCIS (Netherlands)

Gustafson, LA; Kuipers, F; Wiegman, C; Sauerwein, HP; Romijn, JA; Meijer, AJ

2002-01-01

Background/Aims: High-fat (HF) diets cause glucose intolerance. Fibrates improve glucose tolerance. We have tried to obtain information on possible hepatic mechanisms contributing to this effect. Methods: Rats were fed a HF diet, isocaloric with the control diet, for 3 weeks without or with

First pass effect by infusing 99mTc-human serum albumin into the hepatic artery

International Nuclear Information System (INIS)

Ozawa, Takashi; Kimura, Kousaburou; Koyanagi, Yasuhisa

1988-01-01

The fundamental principles of intra-arterial infusion chemotherapy are thought to be increased local drug concentration and the ''first-pass'' effect. The concentration in the rest of the body can only be decreased if there is local elimination of the infused drug before reaching the systemic circulation. This is referred to as the ''first-pass'' effect. In the evaluation of ''first-pass'' effect, the uptake of liver after infusing 99m Tc-human serum albumin ( 99m Tc-HSA) in the hepatic artery by injecting the subcutaneously implanted silicon reservoir was compared with that obtained after intravenous administration of 99m Tc-HSA. In order to remove the factor of portal infusion, each count of liver up take had been continued for only 24 seconds after starting the liver uptake. The results are as follows : for 24 cases excepting 6 cases with catheter obstruction, the mean i.a./i.v. ratio was 7.92 ± 3.34 (range 3.25 to 17.25). Although the elimination rate of drugs in the liver varies with each drug, the infusion of intraarterial chemotherapy should be about 8 times more concentrative than intravenous administration on the ''first-pass'' effect. (author)

Ontogeny of the rat hepatic adrenoceptors

International Nuclear Information System (INIS)

McMillian, M.K.

1985-01-01

Hepatic alpha-1, alpha-2, and beta-2 adrenoceptors were characterized during development of the rat through Scatchard analysis of ( 3 H)-prazosin, ( 3 H)-rauwolscine and ( 125 I)-pindolol binding to washed particle membrane preparations. Major changes in adrenoceptor number occur shortly before birth and at weaning. The fetal rat liver is characterized by a large number of alpha-2 adrenoceptors which falls 10-20 fold at birth. The number of hepatic beta adrenoceptors decreases 30-50% during the third week after birth increases slightly at weaning, then decreases gradually in the adult. Hepatic alpha-1 adrenoceptor number increases 3-5 fold at weaning to become the predominant adrenoceptor in the adult rat liver. The basis for the fall in alpha-2 number at birth remains unclear. The fall in beta receptor number at the end of the second week post-natally appears dependent on increased insulin and corticosterone secretion as well as increased NE release form nerve terminals. The basis for the increase in beta number at weaning and the sex-dependent loss of beta function but not receptor number in the adult rat remains unknown. The dramatic increases in alpha-1 number and function at weaning are dependent on increased adrenocortical secretion, adrenalectomy prevents the normal. This effect of adrenocorticoids might be mediated through glycogen, as glycogen depletion during fasting decreases alpha-1 receptor number and function at weaning are dependent on increased adrenocortical secretion, adrenalectomy prevents the normal. This effect of adrenocorticoids might be mediated through glycogen, as glycogen depletion during fasting decreases alpha-1 receptor number and function. These findings suggest that hepatic adrenoceptor number adapts from the low carbohydrate diet of the suckling rat to the high carbohydrate diet of the adult at weaning

Feature Hepatitis: Hepatitis Can Strike Anyone

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

Directory of Open Access Journals (Sweden)

Maria João Nunes

Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

Metabolic and improved organ scan studies. III. 13N-ammonia metabolic studies in hepatic encephalopathy

International Nuclear Information System (INIS)

Anon.

1976-01-01

Results are reported from an investigation into the nature of hepatic encephalopathy, through study of the uptake and metabolism of 13 N-labeled ammonia by the brain in relation to liver function, in order to develop improved methods for the management of patients with this condition

The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion injury

Science.gov (United States)

Berardo, Clarissa; Siciliano, Veronica; Rizzo, Vittoria; Adorini, Luciano; Richelmi, Plinio

2018-01-01

Background We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. Material and methods Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated. After a 60 min reperfusion, serum, tissue and bile ADMA levels, liver mRNA and protein expression of ADMA transporters (CAT-1, CAT-2A, CAT-2B, OCT-1, MATE-1), and enzymes involved in ADMA synthesis (protein-arginine-N-methyltransferase-1, PRMT-1) and metabolism (dimethylarginine-dimethylaminohydrolase-1, DDAH-1) were measured. Results OCA administration induced a further increase in biliary ADMA levels both in sham and I/R groups, with no significant changes in hepatic ADMA content. A reduction in CAT-1, CAT-2A or CAT-2B transcripts was found in OCA-treated sham-operated rats compared with vehicle. Conversely, OCA administration did not change CAT-1, CAT-2A or CAT-2B expression, already reduced by I/R. However, a marked decrease in OCT-1 and increase in MATE-1 expression was observed. A similar trend occurred with protein expression. Conclusion The reduced mRNA expression of hepatic CAT transporters suggests that the increase in serum ADMA levels is probably due to decreased liver uptake of ADMA from the systemic circulation. Conversely, the mechanism involved in further increasing biliary ADMA levels in sham and I/R groups treated with OCA appears to be MATE-1-dependent. PMID:29346429

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

Science.gov (United States)

Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Pstrategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

Science.gov (United States)

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Effect of rhamnolipids on the uptake of PAHs by ryegrass

International Nuclear Information System (INIS)

Zhu Lizhong; Zhang Ming

2008-01-01

A hydroponic experiment was conducted to investigate the effect of rhamnolipids, a biosurfactant, on the uptake of polycyclic aromatic hydrocarbons (PAHs) by ryegrass. Results showed that rhamnolipids could enhance the uptake of PAHs by ryegrass roots. With increasing concentration of rhamnolipids, the PAH content in ryegrass roots initially increased and then decreased, while the PAH content in ryegrass shoots did not change. Batch studies also showed that the sorption of phenanthrene by fresh ryegrass roots was dependent on rhamnolipid concentration and showed the same trends as the uptake experiment. The increase of permeability of ryegrass root cells with the increase of rhamnolipid concentration may lead to the initial enhancement of PAH content in ryegrass roots, and the decrease of PAH adsorption onto the root surface with further increase of rhamnolipids led to the decrease of PAH content in ryegrass roots. - Rhamnolipids, a biosurfactant, can promote the uptake of PAHs by ryegrass, which indicates a potential application of surfactant-enhanced phytoremediation

Effect of rhamnolipids on the uptake of PAHs by ryegrass

Energy Technology Data Exchange (ETDEWEB)

Zhu Lizhong [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China); Ministry of Education Key Laboratory of Environmental Remediation and Ecological Health, Zhejiang University, Hangzhou, Zhejiang 310029 (China)], E-mail: zlz@zju.edu.cn; Zhang Ming [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China)], E-mail: zhangming@zju.edu.cn

2008-11-15

A hydroponic experiment was conducted to investigate the effect of rhamnolipids, a biosurfactant, on the uptake of polycyclic aromatic hydrocarbons (PAHs) by ryegrass. Results showed that rhamnolipids could enhance the uptake of PAHs by ryegrass roots. With increasing concentration of rhamnolipids, the PAH content in ryegrass roots initially increased and then decreased, while the PAH content in ryegrass shoots did not change. Batch studies also showed that the sorption of phenanthrene by fresh ryegrass roots was dependent on rhamnolipid concentration and showed the same trends as the uptake experiment. The increase of permeability of ryegrass root cells with the increase of rhamnolipid concentration may lead to the initial enhancement of PAH content in ryegrass roots, and the decrease of PAH adsorption onto the root surface with further increase of rhamnolipids led to the decrease of PAH content in ryegrass roots. - Rhamnolipids, a biosurfactant, can promote the uptake of PAHs by ryegrass, which indicates a potential application of surfactant-enhanced phytoremediation.

Hepatic Encephalopathy

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Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice.

Science.gov (United States)

Wei, Zhikui; Lei, Xia; Petersen, Pia S; Aja, Susan; Wong, G William

2014-04-01

Transgenic overexpression of CTRP9, a secreted hormone downregulated in obesity, confers striking protection against diet-induced obesity and type 2 diabetes. However, the physiological relevance of this adiponectin-related plasma protein remains undefined. Here, we used gene targeting to establish the metabolic function of CTRP9 in a physiological context. Mice lacking CTRP9 were obese and gained significantly more body weight when fed standard laboratory chow. Increased food intake, due in part to upregulated expression of hypothalamic orexigenic neuropeptides, contributed to greater adiposity in CTRP9 knockout mice. Although the frequency of food intake remained unchanged, CTRP9 knockout mice increased caloric intake by increasing meal size and decreasing satiety ratios. The absence of CTRP9 also resulted in peripheral tissue insulin resistance, leading to increased fasting insulin levels, impaired hepatic insulin signaling, and reduced insulin tolerance. Increased expression of lipogenic genes, combined with enhanced caloric intake, contributed to hepatic steatosis in CTRP9 knockout mice. Loss of CTRP9 also resulted in reduced skeletal muscle AMPK activation and mitochondrial content. Together, these results provide the genetic evidence for a physiological role of CTRP9 in controlling energy balance via central and peripheral mechanisms.

Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

Science.gov (United States)

Perry, Cassandra H; Smith, William R; St Claire, Robert L; Brouwer, Kenneth R

2011-04-01

Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery. In this study, manual and automated studies are investigated and equivalence is demonstrated. In addition, automated applications using model probe substrates and inhibitors to assess the cholestatic potential of drugs and evaluate hepatic drug transport are examined. The successful automation of this technology provides a more reproducible and less labor-intensive approach, reducing potential operator error in complex studies and facilitating technology transfer.

Hepatic 123I-insulin binding kinetics in non-insulin-dependent (Type 2) diabetic patients after i.v. bolus administration

International Nuclear Information System (INIS)

Oolbekkink, M.; Veen, E.A. van der; Heine, R.J.; Hollander, W. den; Nauta, J.J.P.

1989-01-01

Insulin binding kinetics in the liver were studied in non insulin dependent (Type 2) diabetic patients, by i.v. bolus administration of 123 I-insulin. Eight Type 2 diabetic patients were compared with six male volunteers. Uptake of 123 I-insulin by liver and kidneys was measured by dynamic scintigraphy with a gamma camera during 30 min. Images of liver and kidneys appeared within 2-3 min after administration of 123 I-insulin at a dose of 1 mCi (37 MBq). Peak radioactivity for the liver was found 7.5±0.2 and 6.9±0.3 min after injection for the healthy and the diabetic subjects, respectively (N.S.). The percentage 123 I-insulin hepatic uptake was not significantly different for the diabetic and the healthy subjects. Although a large variation exists for maximal uptake of radioactivity within both groups, the data suggest that binding differences in the liver in Type 2 diabetic patients, as compared to healthy subjects, may not account for hepatic insulin resistance. (orig.)

Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat.

Science.gov (United States)

Ventura, M A; Woollett, L A; Spady, D K

1989-01-01

These studies were undertaken to examine the effect of fish oil, safflower oil, and hydrogenated coconut oil on the major processes that determine the concentration of low density lipoprotein (LDL) in plasma, i.e., the rate of LDL production and the rates of receptor-dependent and receptor-independent LDL uptake in the various organs of the body. When fed at the 20% level, fish oil reduced plasma LDL-cholesterol levels by 38% primarily by increasing LDL receptor activity in the liver. Dietary safflower oil also increased hepatic LDL receptor activity; however, since the rate of LDL production also increased, plasma LDL-cholesterol levels remained essentially unchanged. Hydrogenated coconut oil had no effect on LDL receptor activity but increased the rate of LDL-cholesterol production causing plasma LDL-cholesterol levels to increase 46%. Dietary fish oil had no effect on the receptor-dependent transport of asialofetuin by the liver, suggesting that the effect of fish oil on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physical properties of hepatic membranes. Finally, dietary fish oil increased hepatic cholesteryl ester levels and suppressed hepatic cholesterol synthesis rates, suggesting that the up-regulation of hepatic LDL receptor activity in these animals was not simply a response to diminished cholesterol availability in the liver. PMID:2760200

The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.

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Willemse, S B; Razavi-Shearer, D; Zuure, F R; Veldhuijzen, I K; Croes, E A; van der Meer, A J; van Santen, D K; de Vree, J M; de Knegt, R J; Zaaijer, H L; Reesink, H W; Prins, M; Razavi, H

2015-11-01

Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.

Assessment of hepatic functional reserve for hepatic resection using 99mTc-PMT scintigraphy in comparison with 99mTc-GSA scintigraphy

International Nuclear Information System (INIS)

Sakuma, Atsushi

2000-01-01

99m Tc-diethylenetriamine-pentaacetic acid-galactosyl human serum albumin( 99m Tc-GSA) scintigraphy has been reported as a useful study of hepatic functional reserve recently. We have performed 99m Tc-N-pyridoxyl-5-methyl-tryptophan( 99m Tc-PMT) and 99m Tc-GSA preoperatively for evaluation of hepatic functional reserve and compared the usefulness of those scintigraphy study. Twenty-four patients who were the candidates of hepatic resection underwent 99m Tc-PMT scintigraphy preoperatively. Hepatic blood flow coefficient (K value), the amount of hepatic blood flow (HBF), and the ratio of portal blood flow (PVR) were computed. 99m Tc-GSA scintigraphy was also performed within two weeks of the 99m Tc-PMT scintigraphy, and the ratio of disappearance (HH 15 ) and the hepatic uptake ratio (LHL 15 ) were computed. The relationship between K value, HBF, PVR, HH 15 and LHL 15 was analyzed. Their correlation with other liver function tests was also examined. K value and HBF did not show statistically significant correlations with HH 15 and LHL 15 , PVR correlated statistically significantly HH 15 and LHL 15 . K value correlated with the preoperative values of cholinesterase, Fischer ratio, γ-globulin, ICGR 15 , albumin, and platelet count. There was a statistically significant correlation between LHL 15 and the value of cholinesterase, γ-globulin, platelet count, and Fischer ratio. When the liver resection of subsegmentectomy or more was indicated in 10 patients, nine patients had LHL 15 value less than 0.9 which delineated possibility of poor prognosis. However, judging from K value and HBF, liver resection was considered feasible and it was all successfully performed, resulting in good prognosis. From this study, it is suspected that 99m Tc-GSA scintigraphy reflect the severity of liver fibrosis and the amount of portal blood flows, and 99m Tc-PMT scintigraphy reflect the hepatic blood flow and ability of protein synthesis. It was proved that 99m Tc-PMT scintigraphy is

Effect of iron, taurine and arginine on rat hepatic fibrosis

International Nuclear Information System (INIS)

Song Liangwen; Wang Dewen; Cui Xuemei

1997-01-01

Objective: The promotion role of iron on pathogenesis of hepatic fibrosis and the protective role of taurine and L-arginine against hepatic fibrosis were studied. Method: The model of rat radiation hepatic fibrosis was used. Experimental rats were divided into 0 Gy, 30 Gy, 30 Gy + iron, 30 Gy + taurine and 30 Gy + L-arginine groups. Serum iron, liver tissue hydroxyproline (Hyp) and malondialdehyde (MDA) were measured one and three months respectively after irradiation of hepatic tissue, production and distribution characteristics of hepatic tissue type I and III collagen were observed with a polarizing microscope. Results: Administration of iron agent could significantly increase hepatic tissue MDA content and serum iron concentration, one month after irradiation, hepatic tissue Hyp in 30 Gy + iron group began to increase, and collagen in hepatic tissue obviously increased. Taurine and L-arginine could reduce serum iron concentration and decrease production of hepatic fissure Hyp. Conclusion: Exogenous iron agent could promote early development of radiation hepatic fibrosis; taurine and arginine could diminish pathologic alteration of hepatic fibrosis to a certain extent

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults

Science.gov (United States)

Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

2016-01-01

Background Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. Objective To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. Methods This study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. Results The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (Phepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme. PMID:27093614

Hepatic drug clearance following traumatic injury.

Science.gov (United States)

Slaughter, R L; Hassett, J M

1985-11-01

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Time trend of reported cases and publications: hepatitis E in comparison to hepatitis A - D in Germany from 2001 to 2016.

Science.gov (United States)

Wehmeyer, Malte H; Hartl, Johannes; von Wulffen, Moritz; Lohse, Ansgar W; Pischke, Sven

2018-01-01

The frequency of autochthonous hepatitis E virus (HEV) infections in Western countries has increased since the millennium, probably due to a higher awareness for HEV. The aim of this study was to analyze the epidemiological situation and regional distribution of HEV in comparison to hepatitis A - D in Germany. Data of the reported cases, patients' travel histories, and the regional distribution of hepatitis A - E virus infections from 2001 to 2017 were extracted from databases of the Robert Koch Institute. The number of publications per year on each hepatitis virus was used as a surrogate parameter for scientific awareness. The incidence of HEV infections increased from 31 reported cases in 2001 to 1991 cases in 2016 with a rate of autochthonous HEV infections of 44.4 % in 2001 and 83.9 % in 2016. In 2016, the HEV incidence was 4.4/100 000 in Eastern Germany and 2.0/100 000 in Western Germany. From 2001 to 2016, the numbers of hepatitis A and C virus infections decreased, while the number of hepatitis B virus infections initially decreased followed by an increase since 2014. The incidence of hepatitis D virus infections remained low. The incidence rates of hepatitis A - D virus infections were comparable between Eastern and Western Germany in 2016. There was a strong correlation between publications on HEV and reported HEV cases (Pearson r = 0.9803, p < 0.01). Especially in Eastern Germany, but also in Western Germany, the rate of reported HEV cases and the scientific awareness for this disease increased strongly since 2001. © Georg Thieme Verlag KG Stuttgart · New York.

Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.

Science.gov (United States)

Cotter, David G; Ercal, Baris; d'Avignon, D André; Dietzen, Dennis J; Crawford, Peter A

2014-07-15

Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period. Copyright © 2014 the American Physiological Society.

Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization

International Nuclear Information System (INIS)

Chabrot, Pascal; Cardot, Jean-Michel; Guibert, Pierre; Bouculat, François; Cassagnes, Lucie; Léger-Enreille, Anne; Buc, Emmanuel; Dechelotte, Pierre; Bommelaer, Gilles; Boyer, Louis; Abergel, Armand

2012-01-01

Purpose: To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine. Material and Methods: We analysed plasmatic and hepatic drug concentration in four groups of six mini-pigs each according to the modality of administration of CDDP (1 mg/kg): IV, IHA, IHA with partial embolization using absorbable gelatine (IHA-Pe), and IHA with complete embolization (IHA-Te). Unbounded plasmatic and hepatic platinum concentrations were measured. Concentration and pharmacokinetics parameters were compared using analysis of variance. Results: For all groups, there was a rapid and biexponential decrease in free platinum concentration. Plasmatic terminal half-life (T 1/2 ) was significantly decreased after embolization at 191, 178, 42, and 41 min after IV, IHA, IHA-Pe, and IHA-Te administration, respectively. Maximal plasmatic concentration and systemic exposure to CDDP (AUC 24 ) values were significantly decreased after embolization (C max p = 0.0075; AUC 24 p = 0.0053). Hepatic CDDP concentration rapidly peaked and then decreased progressively. After 24 h, the residual concentration represented 45, 47, 60, and 63 % of C max , respectively, after IV, IHA, IHA-Pe, and IHA-Te. Hepatic T 1/2 and AUC ∞ values were increased after embolization, but the differences were not statistically significant. Conclusion: This preliminary study confirms the feasibility of a pig model to study systemic and hepatic CDDP pharmacokinetics. Systemic exposure is lower after embolization, which could minimize systemic toxicity. Hepatic T 1/2 elimination and hepatic exposition values are increased with IHA compared with IV administration.

Lung damage and pulmonary uptake of serotonin in intact dogs

International Nuclear Information System (INIS)

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

1985-01-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [ 3 H]serotonin and the extravascular volume accessible to [ 14 C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage

Uptake of benzyladenine by excised watermelon cotyledons.

Science.gov (United States)

Lampugnani, M G; Fantelli, R; Longo, G P; Longo, C P; Rossi, G

1981-07-01

The uptake of 8-[(14)C]N(6)-benzyladenine (BA) was studied in excised watermelon (Citrullus vulgaris Schrad.) cotyledons 24 hours after the start of imbibition. The passive nature of this uptake is suggested by the following evidence: (a) no sign of saturation on increasing external concentration of BA; (b) no decrease in uptake under conditions that inhibit ATP synthesis; (c) no change in amount of radioactivity absorbed when cotyledons are frozen and thawed before the uptake test. About two-thirds of the radioactivity taken up is released after 12 hours of washing. If the washing is performed at 2 C very little radioactivity is released.There seems to be a correlation between the level of radioactivity (i.e. of BA + derivatives) present in the cotyledons and the magnitude of hormonal responses that are observed four days after uptake. This relationship holds regardless of whether a given level of radioactivity has been reached after a short period of uptake or after a long period of uptake followed by washing.

Hepatic accumulation of sup(99m)Tc-Sn-diphosphonate

International Nuclear Information System (INIS)

Hayashi, Sanshin; Oyama, Kazuyuki; Hirakawa, Ken; Akaike, Akira; Kogure, Takashi

1977-01-01

Six cases of hepatic accumulation of sup(99m)Tc-Sn-EHDP (ethane-1-hydroxy-1,1-diphosphonate) were encountered among 31 cases of bone scintigram. There were no uniformly common factors in sex, age, disease, liver function, or other laboratory data in these six patients. Colloidal formation was suspected since sup(99m)Tc-Sn-EHDP accumulated in the liver and spleen. EHDP vials from the same kit were analyzed and nothing abnormal was detected. EHDP vials of the same lot number were used in all of 31 cases. Samples of sup(99m)Tc eluate obtained from the same generator used to prepare EHDP and saline eluent from the same stock material used to elute the generator were analyzed. A small amount of aluminum ion and other oxidizer were found but they were thought to be insufficient as factors in the high liver uptake of EHDP because of too small a quantity. pH of sup(99m)Tc eluate was not unusual. Colloidal formation at the time of preparation of sup(99m)Tc-Sn-EHDP is not conceivable since most of the patients undergo bone scintigram without hepatic accumulation. It was assumed that somatic metallic ion substance, serum protein, or other endogeneous matter was responsible for the high liver uptake of EHDP. (auth.)

Dietary effects of marine food intake on intestinal and hepatic enzyme activities in rats.

Science.gov (United States)

González, M; Caride, B; Lamas, A; Taboada, C

2001-03-01

Dietary effects of two diets high in protein from two marine species (Haliotis tuberculata and Anemonia viridis) as compared to a high-quality patron protein such as casein (or casein supplemented with olive oil) on intestinal and hepatic enzymes were studied. After 23 days, the two marine species as diet compared to casein increased the disaccharidase and alkaline phosphatase activities. Feeding Haliotis tuberculata meal produced a decrease on intestinal leucine aminopeptidase activity. The hepatic gamma-glutamyltranspeptidase activity decreased slightly in animals fed Haliotis tuberculata meal. Supplementation of casein with olive oil tended to decrease the intestinal and hepatic enzyme activity.

Hepatitis C

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... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

The Economic Burden of Hepatitis A, B, and C in South Korea.

Science.gov (United States)

Shon, Changwoo; Choi, Hyung-Yun; Shim, Jae-Jun; Park, So-Youn; Lee, Kyung Suk; Yoon, Seok-Jun; Oh, In-Hwan

2016-01-01

The prevalence of hepatitis in South Korea is relatively high compared to that in other high-income countries. For this reason, viral hepatitis infection not only affects the population's health, but also impacts national healthcare costs. This study was performed in order to estimate the individual economic costs of the hepatitis A, B, and C viruses as well as to determine, using nationally representative data, the trends in South Korea with respect to these viruses during the 2008-2011 period. The study found that the prevalence of hepatitis A had decreased, but those of hepatitis B and C had increased overall. The mortality rate of hepatitis C was higher than that of the other two types. The mortality rate of hepatitis B had changed little, whereas that of hepatitis C had risen. The total cost of hepatitis A had decreased, from US $62.2 million to US $45.7 million, although a notable exception occurred in 2009, when the cost was US $126.6 million. Conversely, the total cost of hepatitis B had increased rapidly during the same period, from US $501.4 million to US $607.8 million. Finally, the total cost of hepatitis C had also increased from US $63.9 million to US $90.7 million. The direct costs of hepatitis A, B, and C were estimated to account for approximately 35.5%, 46.6%, and 58.0% of the total, respectively. These findings demonstrate the economic burden associated with hepatitis A, B, and C, and demonstrate the need to establish an effective prevention and management policy for future planning in South Korea.

Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

Science.gov (United States)

Yan, Dong; Chen, Yunbo; Lv, Tao; Huang, Yandi; Yang, Jiezuan; Li, Yongtao; Huang, Jianrong; Li, Lanjuan

2017-10-01

The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, Pdifficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

Increasing Coverage of Hepatitis B Vaccination in China

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Wang, Shengnan; Smith, Helen; Peng, Zhuoxin; Xu, Biao; Wang, Weibing

2016-01-01

Abstract This study used a system evaluation method to summarize China's experience on improving the coverage of hepatitis B vaccine, especially the strategies employed to improve the uptake of timely birth dosage. Identifying successful methods and strategies will provide strong evidence for policy makers and health workers in other countries with high hepatitis B prevalence. We conducted a literature review included English or Chinese literature carried out in mainland China, using PubMed, the Cochrane databases, Web of Knowledge, China National Knowledge Infrastructure, Wanfang data, and other relevant databases. Nineteen articles about the effectiveness and impact of interventions on improving the coverage of hepatitis B vaccine were included. Strong or moderate evidence showed that reinforcing health education, training and supervision, providing subsidies for facility birth, strengthening the coordination among health care providers, and using out-of-cold-chain storage for vaccines were all important to improving vaccination coverage. We found evidence that community education was the most commonly used intervention, and out-reach programs such as out-of-cold chain strategy were more effective in increasing the coverage of vaccination in remote areas where the facility birth rate was respectively low. The essential impact factors were found to be strong government commitment and the cooperation of the different government departments. Public interventions relying on basic health care systems combined with outreach care services were critical elements in improving the hepatitis B vaccination rate in China. This success could not have occurred without exceptional national commitment. PMID:27175710

Hepatitis A through E (Viral Hepatitis)

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... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

LENUS (Irish Health Repository)

Brown, Catherine M

2011-01-01

Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 µg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 ≤ 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

LENUS (Irish Health Repository)

Brown, Catherine M

2012-02-01

Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 microg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 <\\/= 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

Soy compared with milk protein in a western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats

Science.gov (United States)

Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy versus dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF ...

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.

Cadmium, zinc and the uptake of calcium by two crabs, Carcinus maenas and Eriocheir sinensis

International Nuclear Information System (INIS)

Rainbow, P.S.; Black, W.H.

2005-01-01

The uptake of dissolved cadmium and zinc by crustaceans can usually be explained by the passive process of facilitated diffusion involving a transport protein in the membranes of permeable surfaces. Cadmium ions will also enter via uptake routes for calcium, given the similar size of the two free ions. This study has investigated the interaction of cadmium (and comparatively zinc) and calcium uptake in two crabs that show different permeability responses to changes in salinity, with consequently different effects on the uptake of cadmium and zinc with salinity change. Ca uptake rates in Carcinus maenas decreased in reduced salinity (33-15) with the decreased Ca concentration of the medium and increased if the Ca concentration was increased at salinity 20. It is concluded that Ca uptake over the salinity range 33-15 is via apical Ca channels in gill ionocytes, passively down an electrochemical gradient. The Ca uptake rate of Eriocheir sinensis showed no significant decrease over the salinity range 33-10 (probably because of the small differences in an already low Ca uptake rate in this crab against a background of inter-individual variability), but decreased significantly at salinity 5. Added calcium increased the Ca uptake rate of E. sinensis at salinities 15 and 5, supporting the interpretation that Ca uptake in gills is typically passive via apical Ca channels. Cadmium (but not zinc) inhibited calcium uptake in both crabs at 15 salinity, indicating sharing of Ca channels by Cd, but not at salinity 5 (E. sinensis only) when Ca may be taken up into gill ionocytes by another (active?) physiological process

Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization

Energy Technology Data Exchange (ETDEWEB)

Chabrot, Pascal, E-mail: pchabrot@chu-clermontferrand.fr [CHU Clermont-Ferrand, Pole de Radiologie (France); Cardot, Jean-Michel [Universite d' Auvergne Clermont 1, Faculte de Pharmacie, Service de Biopharmacie (France); Guibert, Pierre; Bouculat, Francois [CHU Clermont-Ferrand, Pole Digestif et Hepato-Biliaire (France); Cassagnes, Lucie [CHU Clermont-Ferrand, Pole de Radiologie (France); Leger-Enreille, Anne [Centre Jean Perrin, Service de Biologie (France); Buc, Emmanuel [CHU Clermont-Ferrand, Pole Digestif et Hepato-Biliaire (France); Dechelotte, Pierre [CHU Clermont-Ferrand, Service d' Anatomie-Pathologique (France); Bommelaer, Gilles [CHU Clermont-Ferrand, Pole Digestif et Hepato-Biliaire (France); Boyer, Louis [CHU Clermont-Ferrand, Pole de Radiologie (France); Abergel, Armand [Universite d' Auvergne Clermont 1, Faculte de Medecine, ISIT, UMR CNRS 6284 (France)

2012-12-15

Purpose: To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine. Material and Methods: We analysed plasmatic and hepatic drug concentration in four groups of six mini-pigs each according to the modality of administration of CDDP (1 mg/kg): IV, IHA, IHA with partial embolization using absorbable gelatine (IHA-Pe), and IHA with complete embolization (IHA-Te). Unbounded plasmatic and hepatic platinum concentrations were measured. Concentration and pharmacokinetics parameters were compared using analysis of variance. Results: For all groups, there was a rapid and biexponential decrease in free platinum concentration. Plasmatic terminal half-life (T{sub 1/2}) was significantly decreased after embolization at 191, 178, 42, and 41 min after IV, IHA, IHA-Pe, and IHA-Te administration, respectively. Maximal plasmatic concentration and systemic exposure to CDDP (AUC{sub 24}) values were significantly decreased after embolization (C{sub max}p = 0.0075; AUC{sub 24}p = 0.0053). Hepatic CDDP concentration rapidly peaked and then decreased progressively. After 24 h, the residual concentration represented 45, 47, 60, and 63 % of C{sub max}, respectively, after IV, IHA, IHA-Pe, and IHA-Te. Hepatic T{sub 1/2} and AUC{sub {infinity}} values were increased after embolization, but the differences were not statistically significant. Conclusion: This preliminary study confirms the feasibility of a pig model to study systemic and hepatic CDDP pharmacokinetics. Systemic exposure is lower after embolization, which could minimize systemic toxicity. Hepatic T{sub 1/2} elimination and hepatic exposition values are increased with IHA compared with IV administration.

Hepatitis isquémica Ischemic hepatitis

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Marcos Amuchástegui (h

2006-10-01

Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

Embolization of Hepatic Arterial Branches to Simplify Hepatic Blood Flow Before Yttrium 90 Radioembolization: A Useful Technique in the Presence of Challenging Anatomy

International Nuclear Information System (INIS)

Karunanithy, Narayan; Gordon, Fabiana; Hodolic, Marina; Al-Nahhas, Adil; Wasan, Harpreet S.; Habib, Nagy; Tait, Nicholas P.

2011-01-01

Purpose: In the presence of variant hepatic arterial anatomy, obtaining whole-liver coverage with yttrium 90 (Y90) radioembolization may be challenging. The purpose of this study was to determine whether a technique whereby variant hepatic arterial branches are embolized and then Y90 is administered selectively into one remaining hepatic arterial branch results in whole-liver coverage and effective therapy. A retrospective comparison of treatment response was made between a group of patients who underwent this technique before Y90 administration and a group of patients who received standard Y90 administration as a single dose into the proper hepatic artery or in divided doses into the immediate hepatic artery branches. The rest of the workup and treatment were identical in both groups, including routine embolization of potential nonhepatic, nontarget vessels (e.g., the gastroduodenal artery). Methods: A total of 32 patients (mean age 56.9 years, range 39–77 years) treated with Y90 between June 2004 and March 2008 were analyzed. The primary malignancy was colorectal in 29, breast in 2, and cholangiocarcinoma in 1. Group 1 comprised 20 patients who had no alterations to their hepatic arterial supply. Group 2 comprised 12 cases who had undergone prior embolization of hepatic arterial branches before administration of Y90. The response to treatment was assessed by comparing standardized uptake value (SUV) on the pre- and postprocedure fludeoxyglucose positron emission tomographic studies of representative lesions within the right and left lobes of the liver. Results: In group 1, significant response (P < 0.001) was seen among right lobe lesions but not among left lobe lesions (P = 0.549). In group 2, there was a significant response among both right (P = 0.028) and left (P = 0.014) lobe lesions. No difference was found in the response of right lobe lesions (P = 0.726) between groups 1 and 2; a significantly greater response was found in group 2 compared to group 1 (P

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

Science.gov (United States)

Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

2016-01-01

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

The g0/g1 switch gene 2 is an important regulator of hepatic triglyceride metabolism.

Science.gov (United States)

Wang, Yinfang; Zhang, Yahui; Qian, Hang; Lu, Juan; Zhang, Zhifeng; Min, Xinwen; Lang, Mingjian; Yang, Handong; Wang, Nanping; Zhang, Peng

2013-01-01

Nonalcoholic fatty liver disease is associated with obesity and insulin resistance. Factors that regulate the disposal of hepatic triglycerides contribute to the development of hepatic steatosis. G0/G1 switch gene 2 (G0S2) is a target of peroxisome proliferator-activated receptors and plays an important role in regulating lipolysis in adipocytes. Therefore, we investigated whether G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of G0S2 (Ad-G0S2) potently induced fatty liver in mice. The liver mass of Ad-G0S2-infected mice was markedly increased with excess triglyceride content compared to the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes. G0S2 was found to be co-localized with adipose triglyceride lipase at the surface of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma Low-density lipoprotein (LDL)/Very-Low-density (VLDL) lipoprotein cholesterol level. Plasma High-density lipoprotein (HDL) cholesterol and ketone body levels were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2 overexpression in the liver significantly improved glucose tolerance in mice. Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4-yl) amino)-6-deoxyglucose uptake compared with livers transfected with control adenovirus. Taken together, our results provide evidence supporting an important role for G0S2 as a regulator of triglyceride content in the liver and suggest that G0S2 may be a molecular target for the treatment of insulin resistance and other obesity-related metabolic disorders.

Role of hepatic resection for patients with carcinoid heart disease

DEFF Research Database (Denmark)

Bernheim, A.M.; Connolly, H.M.; Rubin, J.

2008-01-01

OBJECTIVE: To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. PATIENTS AND METHODS: From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005...... nonrandomized study, our data suggest that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis. Eligible patients should be considered for hepatic surgery Udgivelsesdato: 2008/2...

Studies on the evaluation of renal function in hydronephrosis with 99mTc-DMSA renal uptake

International Nuclear Information System (INIS)

Takeda, Masayuki; Katayama, Yasushi; Takahashi, Hitoshi; Sato, Shotaro

1988-01-01

99m Tc-dimercaptosuccinic acid renal uptake (DMSA uptake) was measured in patients with hydronephrosis and we obtained the following conclusions. 1. Grades of hydronephrosis on IVP according to Oka's classification were compared with DMSA uptake. In 73 adult patients, the grade of hydronephrosis paralleled DMSA uptake well, but in 20 children it did not. 2. The changes of DMSA uptake pre- and post-nephrostomy were measured in 21 kidneys in 19 cases with congenital hydronephrosis. DMSA uptake of 7 infantile kidneys significantly increased post-nephrostomy, but in the cases over 1 year old significantly decreased after nephrostomy. DMSA uptake of the contralateral kidney significantly increased after nephrostomy in infants, but it did not change in the group over 1 year old. 3. In 15 kidneys of 13 cases with nephrostomy, DMSA uptake during closure and after opening of the nephrostomy catheter and DMSA uptake due to the radioisotope (RI) accumulated in the renal collecting system were measured. In the group over 1 year old, DMSA uptake decreased after opening nephrostomy nearly all and the extent of the decrease almost agreed with DMSA uptake due to RI accumulated in the renal collecting system. But in infants, DMSA uptake increased after opening nephrostomy in most cases and the extent of the change in DMSA uptake did not agree with DMSA uptake due to RI accumulated in the renal collecting system. (author)

FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

Science.gov (United States)

Verbeke, Len; Mannaerts, Inge; Schierwagen, Robert; Govaere, Olivier; Klein, Sabine; Vander Elst, Ingrid; Windmolders, Petra; Farre, Ricard; Wenes, Mathias; Mazzone, Massimiliano; Nevens, Frederik; van Grunsven, Leo A.; Trebicka, Jonel; Laleman, Wim

2016-01-01

Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis. PMID:27634375

18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

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Tawada A

2014-06-01

Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

Doppler waveform of hepatic vein in patients with chronic hepatitis B; Correlation with histologic grade and stage

International Nuclear Information System (INIS)

Eom, Kyeong Tae; Namkung, Sook; Bae, Sang Hoon; Choi, Young Hee

1999-01-01

To evaluate the relationship between the waveform of the right hepatic vein and the histological grade and stage in patients with chronic hepatitis B. Eighty-seven patients with chronic hepatitis B were examined prospectively by one sonographer. In each patient, Doppler waveform of the right hepatic vein was obtained. Doppler waveform was classified into 3 type, type 0; normal triphasic pattern, type 1; reduced amplitude of phasic oscillation and no reverse flow phase, and type 2; completely flat flow pattern. In the same session, an ultrasound guided liver biopsy was performed and submitted to one pathologist for grading and staging. Duplex doppler ultrasonography of the right hepatic vein was also performed in 12 control subjects with no evidence of liver or heart disease. The doppler waveform was compared with the histologic severity and a statistical analysis was performed. In the control group, all cases had type 0 waveform. In the hepatitis group, there were type 0 waveform in 61 cases (70.1%), type 1 waveform in 22 cases (25.3%) and type 2 waveform in 4 cases (4.6%). The frequency of abnormal waveform is significantly higher in patients with grade 3-4 and stage 3-4 than grade and stage 1-2 (p>0.005). In the hepatitis group, the venous pulsatility index (VPI) was 0.17-0.69 (mean 0.41), and decreased in the highest and mean values when increasing the histologic scores. However, it was nor significant statistically (p>0.05). The frequency of abnormal waveform was correlated with the histologic severity in patients with chronic hepatitis B. The highest and mean values of the VPI were also correlated. However 70.1% of the patients with chronic hepatitis B showed normal waveform. So doppler ultrasonogram of the hepatic vein may be useful for the diagnosis and the differential diagnosis from cirrhosis in patients with chronic hepatitis B by combination of doppler waveform and venous pulsatility index.

Trends and risk factors of hepatitis A in Catalonia after the introduction of a hepatitis A+B vaccination programme.

Science.gov (United States)

Godoy, P; Carmona, G; Manzanares, S; Jane, M; Borràs, E; Camps, N; Álvarez, J; Barrabeig, I; Sala, M-R; Rius, C; Minguell, S; Carol, M; Ferras, J; Domínguez, A

2018-03-31

At the end of 1998, universal hepatitis A+B vaccination of 12 year olds was introduced in Catalonia. The aim was to examine trends in hepatitis A during 2005-2015 and assess risk factors by age group. We carried out an observational epidemiological study of the incidence and risk factors of hepatitis A reported to the surveillance system. Information on exposure was recorded for each case for the 2-6 weeks before symptom onset. Spearman's coefficient was used to evaluate the trends of rates. The chi-square test was used to compare categorical. We studied 2621 hepatitis A cases; the age mean was 26.6 years (SD=18.2), and >50% of cases were in the 20-49 years age group. The incidence decreased from 3.28/100 000 in 2005 to 1.50/100 000 in 2015. The rate for women decreased over time (P = .008), but the reduction was not significant in men (P = .234). Men consistently had higher rates than women with the biggest difference being in the 20-34 years age group (rate 8.8 vs 2.8). The greatest risk factor was travel to an endemic country (42.1%) in the 0-19 years age group and male-to-male sexual contact (18.6%) in the 20-49 years age group. The case fatality rate in adults aged >49 years was 0.4%. In conclusion, the vaccination programme of preadolescents resulted in a reduction in hepatitis A cases. However, a significant amount of cases still appear in immigrants and men who have sex with men. Hepatitis A in adults is an emerging health problem that will require new strategies. © 2018 John Wiley & Sons Ltd.

Athlete’s Hepatitis in a Young Healthy Marathon Runner

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Hafiz Khan

2018-04-01

Full Text Available Athlete’s hepatitis is an uncommon clinical condition characterized by a significant ischemic insult to the liver. The most likely pathogenesis is decreased blood supply to the liver resulting in significant hypoxic hepatocyte injury. We report a case of a 48-year-old healthy young male who presented with athlete’s hepatitis confirmed by liver biopsy after a 14-mile marathon run. To our knowledge, this is the second case of athlete’s ischemic hepatitis reported in the literature. It is a diagnosis worth considering in patients involved in extreme exercise programs.

Accumulation of hepatic Hsp70 and plasma cortisol in Oreochromis ...

African Journals Online (AJOL)

The hepatic isoforms Hsp70, Hsp74 and Hsp76 were identified and quantified from copper exposures. Long-term DDT exposure did not result in significant induction of hepatic Hsp70. An increase in plasma cortisol concentration was associated with a decrease in heat shock protein accumulation after cadmium exposure, ...

F-18 FDG PET/CT imaging of primary hepatic neuroendocrine tumor

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Katsuya Mitamura

2015-01-01

Full Text Available Primary hepatic neuroendocrine tumors (PHNETs are extremely rare neoplasms. Herein, we report a case of a 70-year-old man with a hepatic mass. The non-contrast computed tomography (CT image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F18- fluorodeoxyglucose (18F-FDG positron emission tomography (PET and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body 18F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1. The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by 18F-FDG PET imaging.

Hepatic Encephalopathy

Medline Plus

Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

Hepatic Encephalopathy

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Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

Hepatic erythropoietin response in cirrhosis

DEFF Research Database (Denmark)

Risør, Louise M; Fenger, Mogens; Olsen, Niels Vidiendal

2016-01-01

The main function of erythropoietin (EPO) is to maintain red blood cell mass, but in recent years, increasing evidence has suggested a wider biological role not solely related to erythropoiesis, e.g. angiogenesis and tissue protection. EPO is produced in the liver during fetal life, but the main...... production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total EPO synthesis in healthy controls, but can be up-regulated to 90-100%. However, the hepatic EPO synthesis has been shown not to be adequate for correction of anemia in the absence of renal......, which lead to arterial hypotension, hepatic nephropathy and anemia. An increase in EPO due to renal hypoperfusion, hypoxia and anemia or an EPO-mediated hepato-protective and regenerative mechanism is plausible. However, poor hepatic synthesis capacity, a decreasing co-factor level and inflammatory...

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

Science.gov (United States)

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

International Nuclear Information System (INIS)

Schick, P.K.; Webster, P.

1987-01-01

Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with [ 14 C]-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of [ 14 C]-20:4 into total MK phospholipids, 16% and 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of [ 14 C]-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of [ 14 C]-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

NARCIS (Netherlands)

Ballé, C.; Beuers, U.; ENGELHARDT, R.; JUNGERMANN, K.

1987-01-01

In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were

Hepatic Encephalopathy

Medline Plus

Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits

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Lei Liu

2016-12-01

Full Text Available An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32 were allocated to two equal treatment groups: Fed basal diet (control or fed basal diet with additional 200 mg/kg niacin supplementation (niacin. The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p0.05. However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05. In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.

Hepatocellular carcinoma with marginal superparamagnetic iron oxide uptake on T2*-weighted magnetic resonance imaging: Histopathologic correlation

International Nuclear Information System (INIS)

Ishigami, Kousei; Tajima, Tsuyoshi; Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Kakihara, Daisuke; Nakayama, Tomohiro; Okamoto, Daisuke; Taketomi, Akinobu; Shirabe, Ken; Honda, Hiroshi

2011-01-01

Purpose: To evaluate the characteristics of hepatocellular carcinomas (HCCs) with marginal superparamagnetic iron oxide (SPIO) uptake on T2*-weighted MRI. Materials and methods: The study group consisted of 73 patients with 83 surgically resected HCCs. Preoperative SPIO-enhanced MRI studies were retrospectively reviewed. Marginal SPIO uptake was considered positive if a rim-like or band-like low intensity area was present on SPIO-enhanced T2*-weighted images. The prevalence of marginal SPIO uptake was evaluated. Pathological specimens with hematoxylin and eosin staining and immunohistochemical staining of CD68 were reviewed in HCCs with marginal SPIO uptake and 33 HCCs without marginal SPIO uptake (control group). Results: Ten of 83 (12%) HCCs showed marginal SPIO uptake. All HCCs were hypervascular, and only one nodule showed a nodule-in-nodule appearance on imaging findings. The pathology specimens suggested possible causes of marginal SPIO uptake, including marginal macrophage infiltration in moderately or poorly differentiated HCC (n = 4), residual normal hepatic tissue at the marginal area of confluent multinodular or single nodular with extranodular growth type HCC (n = 3), and a well-differentiated HCC component in nodule-in-nodule type HCC (n = 3). Marginal macrophage infiltration was not seen in the control group. Conclusion: SPIO-enhanced MRI may be able to demonstrate marginal macrophage infiltration in HCC.

Hypolipidemic effect of dietary pea proteins: Impact on genes regulating hepatic lipid metabolism.

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Rigamonti, Elena; Parolini, Cinzia; Marchesi, Marta; Diani, Erika; Brambilla, Stefano; Sirtori, Cesare R; Chiesa, Giulia

2010-05-01

Controversial data on the lipid-lowering effect of dietary pea proteins have been provided and the mechanisms behind this effect are not completely understood. The aim of the study was to evaluate a possible hypolipidemic activity of a pea protein isolate and to determine whether pea proteins could affect the hepatic lipid metabolism through regulation of genes involved in cholesterol and fatty acid homeostasis. Rats were fed Nath's hypercholesterolemic diets for 28 days, the protein sources being casein or a pea protein isolate from Pisum sativum. After 14 and 28 days of dietary treatment, rats fed pea proteins had markedly lower plasma cholesterol and triglyceride levels than rats fed casein (pPea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (ppea protein-fed rats than in rats fed casein (ppea proteins in rats. Moreover, pea proteins appear to affect cellular lipid homeostasis by upregulating genes involved in hepatic cholesterol uptake and by downregulating fatty acid synthesis genes.

Influences of obesity on the immunogenicity of Hepatitis B vaccine.

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Liu, Fang; Guo, Zhirong; Dong, Chen

2017-05-04

Hepatitis B vaccine is regarded as the most effective method for the prevention of hepatitis B virus (HBV) infection. However, several factors such as age, body mass index and immunocompetent state have been reported to be associated with reduced immunization responses. The present commentary was aimed to discuss the influences of obesity on the immunogenicity of hepatitis B vaccines. Available peer-reviewed literatures, practice guidelines, and statistics published on hepatitis B vaccine in obesity between 1973 and 2015. Obesity was significantly associated with non-response to hepatitis B vaccine immunization. The risk of nonresponsiveness of hepatitis B vaccine among obese people increased with BMI. Moreover, the obesity might lead to an increased risk of HBV vaccine-escape mutations. The mechanism responsible for decreased immunization responses in obesity included leptin-induced systemic and B cell intrinsic inflammation, impaired T cell responses and lymphocyte division and proliferation. Therefore, more studies should be performed to analyze the influences of obesity on the immunogenicity of hepatitis B vaccines to improve the immunoprotecive effect of hepatitis B vaccines in future.

Epidemiology and Transmission of Hepatitis A Virus and Hepatitis E Virus Infections in the United States.

Science.gov (United States)

Hofmeister, Megan G; Foster, Monique A; Teshale, Eyasu H

2018-04-30

There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E virus as causes of acute viral hepatitis in North India: a hospital based study.

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Jain, P; Prakash, S; Gupta, S; Singh, K P; Shrivastava, S; Singh, D D; Singh, J; Jain, A

2013-01-01

Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality. The aim of the present study is to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as causes of AVH in a tertiary care hospital of North India. Blood samples and clinical information was collected from cases of AVH referred to the Grade I viral diagnostic laboratory over a 1-year period. Samples were tested for hepatitis B surface antigen, anti-HCV total antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also carried out. Those positive for HBV infection were tested for anti-HDV antibodies. Fisher's exact test was used and a P hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV (26.96%) was identified as the most common cause of acute hepatitis followed by HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV was the most important cause of acute hepatic failure followed by co-infection with HAV and HEV. An indication towards epidemiological shift of HAV infection from children to adults with a rise in HAV prevalence was seen. To the best of our knowledge, this is the first report indicating epidemiological shift of HAV in Uttar Pradesh.

Drier summers cancel out the CO2 uptake enhancement induced by warmer springs.

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Angert, A; Biraud, S; Bonfils, C; Henning, C C; Buermann, W; Pinzon, J; Tucker, C J; Fung, I

2005-08-02

An increase in photosynthetic activity of the northern hemisphere terrestrial vegetation, as derived from satellite observations, has been reported in previous studies. The amplitude of the seasonal cycle of the annually detrended atmospheric CO(2) in the northern hemisphere (an indicator of biospheric activity) also increased during that period. We found, by analyzing the annually detrended CO(2) record by season, that early summer (June) CO(2) concentrations indeed decreased from 1985 to 1991, and they have continued to decrease from 1994 up to 2002. This decrease indicates accelerating springtime net CO(2) uptake. However, the CO(2) minimum concentration in late summer (an indicator of net growing-season uptake) showed no positive trend since 1994, indicating that lower net CO(2) uptake during summer cancelled out the enhanced uptake during spring. Using a recent satellite normalized difference vegetation index data set and climate data, we show that this lower summer uptake is probably the result of hotter and drier summers in both mid and high latitudes, demonstrating that a warming climate does not necessarily lead to higher CO(2) growing-season uptake, even in high-latitude ecosystems that are considered to be temperature limited.

Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

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Jong Hyun Kim

2010-03-01

Full Text Available Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14C

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

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Cedric Simillion

2017-10-01

Full Text Available About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV or C (HCV, with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

Sandwich-Cultured Hepatocytes for Mechanistic Understanding of Hepatic Disposition of Parent Drugs and Metabolites by Transporter-Enzyme Interplay.

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Matsunaga, Norikazu; Fukuchi, Yukina; Imawaka, Haruo; Tamai, Ikumi

2018-05-01

Functional interplay between transporters and drug-metabolizing enzymes is currently one of the hottest topics in the field of drug metabolism and pharmacokinetics. Uptake transporter-enzyme interplay is important to determine intrinsic hepatic clearance based on the extended clearance concept. Enzyme and efflux transporter interplay, which includes both sinusoidal (basolateral) and canalicular efflux transporters, determines the fate of metabolites formed in the liver. As sandwich-cultured hepatocytes (SCHs) maintain metabolic activities and form a canalicular network, the whole interplay between uptake and efflux transporters and drug-metabolizing enzymes can be investigated simultaneously. In this article, we review the utility and applicability of SCHs for mechanistic understanding of hepatic disposition of both parent drugs and metabolites. In addition, the utility of SCHs for mimicking species-specific disposition of parent drugs and metabolites in vivo is described. We also review application of SCHs for clinically relevant prediction of drug-drug interactions caused by drugs and metabolites. The usefulness of mathematical modeling of hepatic disposition of parent drugs and metabolites in SCHs is described to allow a quantitative understanding of an event in vitro and to develop a more advanced model to predict in vivo disposition. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Regulation of Dopamine Uptake by Vasoactive Peptides in the Kidney

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N. L. Rukavina Mikusic

2016-01-01

Full Text Available Considering the key role of renal dopamine in tubular sodium handling, we hypothesized that c-type natriuretic peptide (CNP and Ang-(1-7 may regulate renal dopamine availability in tubular cells, contributing to Na+, K+-ATPase inhibition. Present results show that CNP did not affect either 3H-dopamine uptake in renal tissue or Na+, K+-ATPase activity; meanwhile, Ang-(1-7 was able to increase 3H-dopamine uptake and decreased Na+, K+-ATPase activity in renal cortex. Ang-(1-7 and dopamine together decreased further Na+, K+-ATPase activity showing an additive effect on the sodium pump. In addition, hydrocortisone reversed Ang-(1-7-dopamine overinhibition on the enzyme, suggesting that this inhibition is closely related to Ang-(1-7 stimulation on renal dopamine uptake. Both anantin and cANP (4-23-amide did not modify CNP effects on 3H-dopamine uptake by tubular cells. The Mas receptor antagonist, A-779, blocked the increase elicited by Ang-(1-7 on 3H-dopamine uptake. The stimulatory uptake induced by Ang-(1-7 was even more pronounced in the presence of losartan, suggesting an inhibitory effect of Ang-(1-7 on AT1 receptors on 3H-dopamine uptake. By increasing dopamine bioavailability in tubular cells, Ang-(1-7 enhances Na+, K+-ATPase activity inhibition, contributing to its natriuretic and diuretic effects.

HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARγ

International Nuclear Information System (INIS)

Kim, Kook Hwan; Hong, Sung Pyo; Kim, KyeongJin; Park, Min Jung; Kim, Kwang Jin; Cheong, JaeHun

2007-01-01

Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPARγ (peroxisome proliferators-activated receptor γ) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPARγ. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfected with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPARγ transcriptional activity. However, HCV core protein had no effect on PPARγ gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection

Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study.

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Shaoxia Xu

Full Text Available The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010-2011. Positive human immunodeficiency virus tests were confirmed via western blotting.Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively than in women (4.45% and 0.021%, respectively. The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%, Emergency (1.71%, and Dermatology and Sexually Transmitted Diseases (1.12% departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60-70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.During 2010-2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with

Decreasing prevalence of Hepatitis B and absence of Hepatitis C Virus infection in the Warao indigenous population of Venezuela

Science.gov (United States)

Blanco, Ruth Y.; Loureiro, Carmen L.; Sulbarán, Yoneira F.; Maes, Mailis; de Waard, Jacobus H.; Rangel, Héctor R.

2018-01-01

Prevalence and molecular epidemiology studies for hepatitis B (HBV) and C (HCV) virus are scarce in Warao Amerindians from Venezuela, where an epidemic of human immunodeficiency virus type 1 (HIV-1) has recently been documented. To carry out a molecular epidemiology analysis of hepatitis B (HBV) and C (HCV) virus in Warao individuals from the Delta Amacuro State of Venezuela. A total of 548 sera were tested for serological and molecular markers for HBV and HCV. The prevalence of active infection (presence of HBV surface antigen, HBsAg), exposure to HBV (presence of Antibody to HBV core antigen, anti-HBc) and anti-HCV, was 1.8%, 13% and 0% respectively. HBV exposure was significantly lower in men below 18 years old and also lower than rates previously reported in other Amerindian communities from Venezuela. Thirty one percent (31%, 25/80) of individuals without evidence of HBV infection exhibited anti-HBs titer ≥ 10U.I / ml, being significantly more frequent in individuals younger than 20 years. A higher HBV exposure was observed among HIV-1 positive individuals (33% vs 11%, p <0.005). A high prevalence of occult HBV infection was also observed (5.6%, 11/195). Phylogenetic analysis of S gene and complete HBV genomes showed that F3 is the only circulating subgenotype, different from the F2 subgenotype found in 1991 in this population. These results suggest a recent introduction of subgenotype F3, with a low divergence among the isolates. These results highlight the importance of molecular epidemiology studies for viral control, and support the effectiveness of vaccination in reducing transmission of HBV. PMID:29799873

Fibronectin and Kupffer cell function in fulminant hepatic failure

International Nuclear Information System (INIS)

Imawari, M.; Hughes, R.D.; Gove, C.D.; Williams, R.

1985-01-01

The relationship between plasma fibronectin, in vitro plasma opsonic activity, which measures the biological activity of fibronectin, and in vivo Kupffer cell function, as assessed by the systemic clearance of microaggregated [ 125 I]albumin, were determined simultaneously in 15 patients with fulminant hepatic failure and 12 normal subjects. Both the plasma fibronectin and plasma opsonic activity were significantly reduced in patients with fulminant hepatic failure, while the systemic clearance of microaggregated albumin was decreased. There was a significant correlation between plasma fibronectin and the plasma opsonic activity on admission, but no correlation could be detected between either parameter and the clearance of microaggregated albumin. A gelatin-derived plasma expander was shown to block the plasma opsonic activity both in vitro and in vivo. The low plasma fibronectin and decreased clearance of microaggregated albumin in fulminant hepatic failure reflect different aspects of the overall impairment of Kupffer cell function

Failure to incriminate hepatitis B, hepatitis C, and hepatitis E viruses in the aetiology of fulminant non-A non-B hepatitis.

OpenAIRE

Mutimer, D; Shaw, J; Neuberger, J; Skidmore, S; Martin, B; Hubscher, S; McMaster, P; Elias, E

1995-01-01

Sporadic non-A, non-B hepatitis is the most common indication for liver transplantation in patients presenting with fulminant and subacute liver failure. This study used serological, histological, and molecular biological techniques to examine specimens from 23 consecutive patients transplanted for sporadic non-A, non-B hepatitis. No evidence was found of hepatitis C virus, hepatitis E virus, or 'cryptic' hepatitis B virus infection.

Hepatitis

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... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

Science.gov (United States)

Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

2006-06-01

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Quantitative Assessment of Hepatic Fibrosis by Contrast-enhanced Ultrasonography

Institute of Scientific and Technical Information of China (English)

Ming-bo Zhang; En-ze Qu; Ji-Bin Liu; Jin-rui Wang

2011-01-01

Objective To explore the contrast-enhanced ultrasonographic features for quantitative assessment of hepatic fibrosis.Methods 86 patients with chronic viral hepatitis B were enrolled in this study from March 2007 to August 2009.The patients were classified into 5 groups (S0-S4) according to fibrosis stage evaluated with ultrasound guided liver biopsy.New contrast-enhanced ultrasonography (CEUS) features including area under the time-intensity curve (TIC) of portal venous phase/hepatic arterial phase (Qp/Qa) and intensity of portal venons phase/hepatic arterial phase (Ip/Ia) were used to detect the blood supply ratio (portal vein/hepatic artery) in each group.Arrival time of portal vein trunk (Tp) and decreasing rate of TIC (β) were also analyzed.Results Qp/Qa and Ip/Ia decreased from So to S4,while Tp and β increased These 4 features were significantly correlated with the degree of fibrosis (P＜0.001) and were significantly different among the five groups (P＜0.001).Sensitivity and specificity of Ip/Ia were 80% and 86% for groups ≥S1,75% and 86% for groups ≥ S2,71% and 84% for groups ≥ S3,and 76% and 80% for group S4,respectively.Sensitivity and specificity of Qp/Qa were 70% and 88% for groups ≥ S1,80% and 76% for groups ≥ S2,74% and 70% for groups ≥ S3,and 81% and 95% for group S4,respectively.Conclusion Ip/Ia and Qp/Qa could be adopted as reliable,non-invasive features for quantitative assessment of hepatic fibrosis.

Factors influencing intracellular uptake and radiosensitization by 2-nitroimidazoles in vitro

International Nuclear Information System (INIS)

Brown, D.M.; Gonzalez-Mendez, R.; Brown, J.M.

1983-01-01

In this study it is shown that the radiosensitization of hypoxic Chinese hamster ovary (HA-1) cells in vitro by misonidazole (MIS) and other 1-substituted 2-nitroimidazoles depends on the rate and extent of intracellular uptake of these radiosensitizers, which in turn is governed by their lipophilicity [expressed as the octanol:water partition coefficient (P)]. As the lipophilicity of the compounds decreased, the rate of drug entry into the cells was slower, and below P values of approximately 0.05, peak intracellular drug concentrations were found to be lower than that of MIS (P=0.43). In addition, the number of hydroxyl groups on the side chain of the nitroimidazole molecule influenced the uptake of drug into the cells. For compounds of similar P, but differing in the number of side-chain hydroxyl groups, the addition of a single hydroxyl group to the molecule decreased the amount of drug entering the cell by a factor of approximately 2. These compounds enter the cell by nonmediated passive diffusion since altering the energy (ATP) capacity of the cell by 2-deoxyglucose did not affect uptake. It is also shown that increases in temperature or decreases in pH can increase the intracellular uptake of MIS. For example, equal intracellular and extracellular concentrations (100% uptake) of MIS were obtained if cells were heated to 44-45 0 C for 15 min compared to 20-40% uptake at 37 0 C. Increases in MIS uptake by factors of 2 to 3 could be demonstrated within 30 min when cells were incubated in Hanks' balanced salt solution at pH between 6.0 and 6.3 without loss of cell viability. In addition, MIS uptake in aerobic cultured cells varied from 15 to 60% depending on the cell line and culure conditions used

Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis in Mongolia: The first report of the full genome sequence of a novel genotype 1 hepatitis E virus strain.

Science.gov (United States)

Tsatsralt-Od, Bira; Primadharsini, Putu Prathiwi; Nishizawa, Tsutomu; Ohnishi, Hiroshi; Nagashima, Shigeo; Takahashi, Masaharu; Jirintai, Suljid; Nyamkhuu, Dulmaa; Okamoto, Hiroaki

2018-01-01

In January 2012, Mongolia started a hepatitis A vaccination program, which has not yet been evaluated. The first occurrence of autochthonous acute hepatitis E in 2013, caused by genotype 4 hepatitis E virus (HEV), suggests the need for a routine study to monitor its prevalence. One hundred fifty-four consecutive patients who were clinically diagnosed with acute hepatitis between 2014 and 2015 in Ulaanbaatar, Mongolia were studied. By serological and molecular testing followed by sequencing and phylogenetic analysis, only one patient (0.6%) was diagnosed with acute hepatitis A, caused by genotype IA hepatitis A virus (HAV), and 32 (20.8%) patients were diagnosed with acute hepatitis E, caused by genotype 1 HEV. The 32 HEV isolates obtained in this study shared 99.5-100% nucleotide identity and were grouped into a cluster separated from those of subtypes 1a to 1f. Upon comparison of p-distances over the entire genome, the distances between one representative HEV isolate (MNE15-072) and 1a-1f strains were 0.071-0.137, while those between 1b and 1c were 0.062-0.070. In conclusion, the prevalence of acute hepatitis A has decreased in Mongolia since the start of the vaccination program, while the monophyletic genotype 1 HEV strain of a probably novel subtype has been prevalent. © 2017 Wiley Periodicals, Inc.

Hepatitis Vaccines

OpenAIRE

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

Age-related normal uptake of 99mTc-MDP in the lower spine

International Nuclear Information System (INIS)

Sundkvist, G.M.G.; Lilja, B.; Mattsson, S.

1997-01-01

Aim: The uptake of 99m Tc-MDP in the lower spine was quantified in connection with ordinary bone scintigraphy. Methods: Fifty-seven women and seventy-two men (aged 20-69 y), with no signs of metabolic or malignant disease and no history of back pain or atraumatic fractures, were included in the study. Results: The women showed an increase in 99m Tc-MDP uptake from the age of 20 y to about 45 y with a decrease from the time of menopause. In contrast to women, the uptake in men showed a slight decrease from the age of 20 y to about 50 y and thereafter a more marked decrease was seen. The major difference between men and women is the high premenopausal uptake in the female skeleton. Conclusion: An understanding of age-related changes in 99m Tc-MDP uptake, which are indices of the skeletal metabolism, is of importance especially in prevention and treatment of osteoporosis, a common disorder in postmenopausal women. (orig.) [de

Hepatitis Vaccines

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Sina Ogholikhan

2016-03-01

Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

Hepatitis Vaccines

Science.gov (United States)

Ogholikhan, Sina; Schwarz, Kathleen B.

2016-01-01

Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

Primary hepatic artery embolization in pediatric blunt hepatic trauma.

Science.gov (United States)

Ong, Caroline C P; Toh, Luke; Lo, Richard H G; Yap, Te-Lu; Narasimhan, Kannan

2012-12-01

Non-operative management of isolated blunt hepatic trauma is recommended except when hemodynamic instability requires immediate laparotomy. Hepatic artery angioembolization is increasingly used for hepatic injuries with ongoing bleeding as demonstrated by contrast extravasation on the CT scan. It is used primarily or after laparotomy to control ongoing hemorrhage. Hepatic angioembolization as part of multimodality management of hepatic trauma is reported mainly in adults, with few pediatric case reports. We describe our institution experience with primary pediatric hepatic angioembolization and review the literature with regard to indications and complications. Two cases (3 and 8 years old), with high-grade blunt hepatic injuries with contrast extravasation on the CT scan were successfully managed by emergency primary hepatic angioembolization with minimal morbidity and avoided laparotomy. To date, the only reports of pediatric hepatic angioembolization for trauma are 5 cases for acute bleeding and 15 delayed cases for pseudoaneurysm. The role of hepatic angioembolization in the presence of an arterial blush on CT in adults is accepted, but contested in a pediatric series, despite higher transfusion rate and mortality rate. We propose that hepatic angioembolization should be considered adjunct treatment, in lieu of, or in addition to emergency laparotomy for hemostasis in pediatric blunt hepatic injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

Science.gov (United States)

Laparra, José Moisés; Haros, Monika

2018-03-01

Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells.

Science.gov (United States)

Wang, Xin; Low, Xinyi Casuarine; Hou, Weixin; Abdullah, Lissa Nurrul; Toh, Tan Boon; Mohd Abdul Rashid, Masturah; Ho, Dean; Chow, Edward Kai-Hua

2014-12-23

Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond-drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers.

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

Directory of Open Access Journals (Sweden)

Zhifang Wang

Full Text Available Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV. Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China, with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program.To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades.This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province.The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001. During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001. Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases.Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

Mincle Signaling Promotes Con-A Hepatitis

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Greco, Stephanie H.; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R.; Nagaraj, Savitha V.; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E.; Katz, Steven C.; Miller, George

2016-01-01

Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con-A hepatitis. Acute liver injury was assessed in the murine Con-A hepatitis model using C57BL/6, Mincle−/−, and Dectin-1−/− mice. The role of C/EBPβ and HIF-1α signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con-A hepatitis. Most significantly, Mincle deletion or blockade protected against Con-A hepatitis whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con-A hepatitis and inhibition of both C/EBPβ and HIF1-α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con-A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. PMID:27559045

Mincle Signaling Promotes Con A Hepatitis.

Science.gov (United States)

Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R; Nagaraj, Savitha V; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E; Katz, Steven C; Miller, George

2016-10-01

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ-related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation. Copyright © 2016 by The American Association of Immunologists, Inc.

Right Hepatic Artery: A Cadaver Investigation and Its Clinical Significance

Directory of Open Access Journals (Sweden)

Usha Dandekar

2015-01-01

Full Text Available The right hepatic artery is an end artery and contributes sole arterial supply to right lobe of the liver. Misinterpretation of normal anatomy and anatomical variations of the right hepatic artery contribute to the major intraoperative mishaps and complications in hepatobiliary surgery. The frequency of inadvertent or iatrogenic hepatobiliary vascular injury rises with the event of an aberrant anatomy. This descriptive study was carried out to document the normal anatomy and different variations of right hepatic artery to contribute to existing knowledge of right hepatic artery to improve surgical safety. This study conducted on 60 cadavers revealed aberrant replaced right hepatic artery in 18.3% and aberrant accessory right hepatic artery in 3.4%. Considering the course, the right hepatic artery ran outside Calot’s triangle in 5% of cases and caterpillar hump right hepatic artery was seen in 13.3% of cases. The right hepatic artery (normal and aberrant crossed anteriorly to the common hepatic duct in 8.3% and posteriorly to it in 71.6%. It has posterior relations with the common bile duct in 16.7% while in 3.4% it did not cross the common hepatic duct or common bile duct. The knowledge of such anomalies is important since their awareness will decrease morbidity and help to keep away from a number of surgical complications.

Viral Hepatitis

Science.gov (United States)

... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

Amendment damages the function of continuous flooding in decreasing Cd and Pb uptake by rice in acid paddy soil.

Science.gov (United States)

Ye, Xinxin; Li, Hongying; Zhang, Ligan; Chai, Rushan; Tu, Renfeng; Gao, Hongjian

2018-01-01

Combinations of remediation technologies are needed to solve the problem of soil contamination in paddy rice, due to multiple potential toxic elements (PTEs). Two potential mitigation methods, water management and in-situ remediation by soil amendment, have been widely used in treatment of PTE-polluted paddy soil. However, the interactive relationship between soil amendment and water management, and its influence on the accumulation of PTEs in rice are poorly understood. Greenhouse pot experiments were conducted to examine the effects of phosphate amendment on Cd and Pb availability in soil and their influence on Cd and Pb uptake into rice, on Fe and P availability in soil, and on the alteration of Fe amount and compartment on root surface among different water management strategies. Results indicated that Cd and Pb content in the shoot and grain were significantly affected by the different water management strategies in nonamended soils, and followed the order: wetting irrigation > conventional irrigation > continuous flooding. The application of phosphate amendment significantly decreased the variations of Cd and Pb absorption in shoot and grain of rice among different water treatments. The reasons may be attributed to the enhancement of P availability and the decrease of Fe availability in soil, and the decreased variations of Fe 2+ /Fe 3+ content in root coating after the application of phosphate amendment. These results suggested that the simultaneous use of phosphate amendment and continuous flooding to immobilize Cd and Pb, especially in acid paddy soils, should be avoided. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.

Science.gov (United States)

Machado, Mariana V; Oliveira, António G; Cortez-Pinto, Helena

2011-09-01

Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta-analysis to evaluate HS prevalence and risk factors, in HBV infection. Standard guidelines for performance of meta-analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random-effects model and DerSimonian-Laid method. Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45-0.67], P SMD 2.17, 95%CI [1.23, 3.11], P SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10-2.15], P = 0.011) and negatively with HBV DNA (SMD -74.12, 95%CI [-82.93, -65.31], P infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Positron emission tomography of hepatic first-pass metabolism of ammonia in pig

International Nuclear Information System (INIS)

Keiding, S.; Munk, O.L.; Roelsgaard, K.; Bender, D.; Bass, L.

2001-01-01

Hepatic first-pass metabolism plays a key role in metabolic regulation and drug metabolism. Metabolic processes can be quantified in vivo by positron emission tomography scanning (PET). We wished to develop a PET technique to measure hepatic first-pass metabolism of ammonia. Seven anaesthetised pigs were given positron-labelled ammonia, 13 NH 3 , into the portal vein and into the vena cava as successive 2-min infusions followed by 22-min dynamic liver scanning. Vena cava infusion data were used to account for recirculation of tracer and metabolites following the portal vein infusion. The scan data were analysed by a model of sinusoidal zonation of ammonia metabolism with periportal urea formation and perivenous formation of glutamine. The hepatic extraction fraction of 13 NH 3 was 0.73±0.16 (mean±SD, n=7 pigs). Values of clearance of ammonia to urea and to glutamine were obtained, as were rate constants for washout of these two metabolites. Overall, the modelling showed half of the ammonia uptake to be converted to urea and half to glutamine. The washout rate constant for glutamine was about one-tenth of that for urea. We conclude that hepatic first-pass metabolism of ammonia was successfully assessed by PET. (orig.)

Trends in mortality burden of hepatocellular carcinoma, cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: An analysis of death certificate data.

Science.gov (United States)

Ramírez-Soto, Max Carlos; Ortega-Cáceres, Gutia; Cabezas, César

2017-07-05

The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960-1990) and after (1991-2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28-10.48%; P<0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20-16.10%; P<0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70-50.30%; P<0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P<0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P<0.026) decreased in 5-14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15years, following implementation of the vaccination program against hepatitis B. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cu uptake and turnover in both Cu-acclimated and non-acclimated rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Grosell, M.; Hogstrand, C.; Wood, C.M.

1997-01-01

-acclimation clearly involves changes in copper accumulation kinetics in the plasma. The acclimated fish showed a 65% reduced Cu-64 accumulation after 65 h and an increased turnover of Cu in the plasma compared to the non-acclimated fish. Total Cu in the plasma increased by 59% after 3 h of exposure in the non...... aortic catheter. By measuring both Cu-64 accumulation and total Cu concentrations, we were able to analyse the ongoing uptake and turnover of ambient Cu, independent of any Cu already present in the fish. Plasma accounted for at least 90% of the Cu-64 labelled Cu present in the blood and Cu...... h of exposure. Acclimation did not have an unambiguous effect on branchial Cu uptake and differences in branchial uptake could not explain the reduced accumulation in the plasma. The rapidly exchangeable Cu pools were 54% in the gills and 33% in the liver, suggesting a considerable hepatic Cu...

Cysteine- and glutathione-mediated uptake of lead and cadmium into Zea mays and Brassica napus roots

International Nuclear Information System (INIS)

Vadas, Timothy M.; Ahner, Beth A.

2009-01-01

This study examines a new mechanism for the uptake of Pb and Cd into Brassica napus and Zea mays roots. During hydroponic experiments, the uptake of Pb and Cd was enhanced in the presence of cysteine and glutathione, whereas no or very low uptake was observed in EDTA and penicillamine controls. Uptake rates were also enhanced after pre-exposure to cysteine or glutathione and inhibited in the presence of vanadate, suggesting a biological mechanism of uptake. Increasing concentrations of glutathione in solution resulted in decreasing Pb uptake rates, indicating competition for transport between free-glutathione and Pb-glutathione species. Pb uptake in the presence of increasing cysteine concentrations resulted in decreased uptake initially but linearly increasing uptake at higher concentrations. Experimentation showed concentration dependent Pb uptake rates. We speculate that there are specific transporters for these thiol ligands and describe what barriers remain for application of this novel transport mechanism in chelator-assisted phytoremediation. - Cysteine and glutathione mediate the transport of lead and cadmium into plant roots.

Cysteine- and glutathione-mediated uptake of lead and cadmium into Zea mays and Brassica napus roots

Energy Technology Data Exchange (ETDEWEB)

Vadas, Timothy M., E-mail: tvadas@umbc.ed [Department of Biological and Environmental Engineering, Cornell University, 320 Riley-Robb Hall, Ithaca, NY 14853 (United States); Ahner, Beth A., E-mail: baa7@cornell.ed [Department of Biological and Environmental Engineering, Cornell University, 320 Riley-Robb Hall, Ithaca, NY 14853 (United States)

2009-08-15

This study examines a new mechanism for the uptake of Pb and Cd into Brassica napus and Zea mays roots. During hydroponic experiments, the uptake of Pb and Cd was enhanced in the presence of cysteine and glutathione, whereas no or very low uptake was observed in EDTA and penicillamine controls. Uptake rates were also enhanced after pre-exposure to cysteine or glutathione and inhibited in the presence of vanadate, suggesting a biological mechanism of uptake. Increasing concentrations of glutathione in solution resulted in decreasing Pb uptake rates, indicating competition for transport between free-glutathione and Pb-glutathione species. Pb uptake in the presence of increasing cysteine concentrations resulted in decreased uptake initially but linearly increasing uptake at higher concentrations. Experimentation showed concentration dependent Pb uptake rates. We speculate that there are specific transporters for these thiol ligands and describe what barriers remain for application of this novel transport mechanism in chelator-assisted phytoremediation. - Cysteine and glutathione mediate the transport of lead and cadmium into plant roots.

Hepatitis C virus infection epidemiology among people who inject drugs in Europe

DEFF Research Database (Denmark)

Wiessing, Lucas; Ferri, Marica; Grady, Bart

2014-01-01

BACKGROUND: People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity......, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. METHODS AND FINDINGS: We searched MEDLINE, EMBASE and Cochrane Library for publications between 1...... January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability...

[11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

International Nuclear Information System (INIS)

Guiducci, Letizia; Jaervisalo, Mikko; Kiss, Jan; Nagren, Kjell; Viljanen, Antti; Naum, Alexandru G.; Gastaldelli, Amalia; Savunen, Timo; Knuuti, Juhani; Salvadori, Piero A.; Ferrannini, Ele; Nuutila, Pirjo; Iozzo, Patricia

2006-01-01

Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [ 11 C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [ 11 C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [ 11 C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P≤.03), suggesting faster clearance. Levels of unmetabolized [ 11 C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [ 11 C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92±1% and 82±6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [ 11 C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional

Blood disappearance rate of /sup 198/Au-colloid and changes of hepatic blood flow during position change in normal persons and in patients with various hepatic diseases

Energy Technology Data Exchange (ETDEWEB)

Cho, B Y [Capital Armed Forces General Hospital, Seoul (Republic of Korea); Hong, K S; Koh, C S; Lee, M [Seoul National Univ., Seoul (Republic of Korea). Coll. of Medicine

1977-01-01

To evaluate the diagnostic significance of the blood disappearance rate of /sup 198/Au-colloid and to evaluate the change of hepatic blood flow during position change from supine to erect, we measured the half time of blood disappearance rate of 7,1/sup 98/Au-colloid using external counting method in 94 normal persons and in 77 patients with various hepatic diseases. The results obtained were as follows: 1. In normal control, the mean blood disappearance half time of /sup 198/Au-colloid in supine position was 2.7+-0.4 minutes. There was no significant difference of hepatic blood flow in age and sex. 2. In acute hepatitits, chronic hepatitis and hepatic cirrhosis, the mean blood disappearance half times in supine position were 3.0+-0.45, 3.5+-0.74, 7.2+-3.6 minutes respectively. The hepatic blood flow of the patients with chronic hepatitis and hepatic cirrhosis were significantly decreased than that of normal control. 3. In the normal control and acute hepatitis, the decreaces of the hepatic blood flow during the position change from supine to erect were 27.7% and 22.6% respectively.

The blood disappearance rate of 198Au-colloid and changes of hepatic blood flow during position change in normal persons and in patients with various hepatic diseases

International Nuclear Information System (INIS)

Cho, B.Y.; Hong, K.S.; Koh, C.S.; Lee, M.

1977-01-01

To evaluate the diagnostic significance of the blood disappearance rate of 198 Au-colloid and to evaluate the change of hepatic blood flow during position change from supine to erect, we measured the half time of blood disappearance rate of 7,1 98 Au-colloid using external counting method in 94 normal persons and in 77 patients with various hepatic diseases. The results obtained were as follows: 1. In normal control, the mean blood disappearance half time of 198 Au-colloid in supine position was 2.7+-0.4 minutes. There was no significant difference of hepatic blood flow in age and sex. 2. In acute hepatitits, chronic hepatitis and hepatic cirrhosis, the mean blood disappearance half times in supine position were 3.0+-0.45, 3.5+-0.74, 7.2+-3.6 minutes respectively. The hepatic blood flow of the patients with chronic hepatitis and hepatic cirrhosis were significantly decreased than that of normal control. 3. In the normal control and acute hepatitis, the decreaces of the hepatic blood flow during the position change from supine to erect were 27.7% and 22.6% respectively. (author)

The role of computed tomography in blunt hepatic injury

International Nuclear Information System (INIS)

Kaji, Tatsumi

1988-01-01

Computed tomography (CT) images and medical records of 283 patients with blunt abdominal trauma were reviewed. There were 67 patients with hepatic injury. Liver was the most frequently injured organ in blunt abdominal trauma. Most hepatic injuries occurred in the right lobe of the liver. Of the 67 patients with hepatic injury, 60 patients had associated other injuries. There was a high incidence of associated lung injuries (35.8 %). Of importance is the high incidence of associated head injuries (22.4 %), because, in some patients such as those with concomitant head trauma, abdominal symptom is not obvious. The associated hemoperitoneum were correlated with the mode of therapy used in each case (operative vs. nonoperative). 32 patients with hepatic injury but no hemoperitoneum were managed nonoperatively. 9 patients with hepatic injury and little hemoperitoneum were also managed conservatively. 22 patients with high density hemoperitoneum were surgically treated. By combining information on the clinical state of the patient and CT finding, therapy of hepatic injury can be individualized and the incidence of nontherapeutic laparotomies decreased. (author)

Hepatitis B

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... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

Hepatic Encephalopathy

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Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.

Science.gov (United States)

Niriella, Madunil Anuk; Kobbegala, Vipuli Jayendra; Karalliyadda, Hasnatha Nuwan; Ranawaka, Chamila Kumara; de Silva, Arjuna Priyadarshin; Dassanayake, Anuradha Supun; de Silva, Hithanadura Janaka

2017-07-21

As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.

Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

International Nuclear Information System (INIS)

Miles, K.A.; Keith, C.J.; Griffiths, M.R.; Fuentes, M.; Bunce, I.

2002-01-01

Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

Energy Technology Data Exchange (ETDEWEB)

Miles, K A [Southernex Imaging Group, QLD (Australia); Queensland University of Technology, QLD (Australia); Keith, C J [Southernex Imaging Group, QLD (Australia); Wesley Research Institute, QLD (Australia); Griffiths, M R [Queensland University of Technology, QLD (Australia); Fuentes, M [Southernex Imaging Group, QLD (Australia); Bunce, I [Wesley Research Institute, QLD (Australia)

2002-07-01

Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc.

Alcohol and Hepatitis

Science.gov (United States)

... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

Hepatitis C: Treatment

Science.gov (United States)

... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

Effects of β-hydroxy β-methyl butyrate supplementation to sows in late gestation on absorption and hepatic metabolism of glucose and amino acids during transition

DEFF Research Database (Denmark)

Flummer, Christine; Lyby, H; Storli, K S

2012-01-01

A multicatheter sow model was established to study the effects of dietary β-hydroxy β-methyl butyrate (HMB) supplementation on net portal flux (NPF) and net hepatic flux (NHF) of HMB, glucose, and the AA Ala, Gly, Ile, Leu, Phe, Tyr, and Val. Eight second parity sows were fitted with permanent...... the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)2/kg BW mixed in one third of the morning meal from day –10 until parturition. Net portal flux of HMB was affected by treatment (Trt; P HMB sows at 6.9 mmol/h 30 min after the morning meal...... and then decreased towards preprandial level (0.0 mmol/h) 3.5 h after the meal, revealing that dietary HMB was rapidly absorbed from the intestine. The NHF of HMB tended to be affected by Trt (P = 0.06) showing a small hepatic uptake of HMB (1.1 mmol/h) in HMB sows. Net portal flux of glucose and all measured AA...

Heavy metals and their radionuclides uptake by Bacillus Licheniformis

International Nuclear Information System (INIS)

Ramadan, A.A.; Ahmed, M.M.; Abo-state, M.A.M.; Sarhan, M.; Faroqe, M.

2007-01-01

Bacillus licheniformis is a gram positive spore forming bacterium. Different concentrations of cobalt affected the ability of Co uptake and growth of Bacillus licheniformis. As the concentration increased, both the uptake and growth were decreased. Maximum Co uptake was found at ph 7.0, while for growth was ph 8.0. The optimum temperature for uptake and growth was 40 degree C and 20% inoculum size represents the maximum cobalt uptake by Bacillus licheniformis. Also, maximum uptake was recorded after 72 hours, incubation period. As the concentration of cesium was increased till 400 mg/l, the uptake was also increased. The optimum cesium uptake and growth was at ph 8.0. The optimum growth was at 45 degree C while Cs uptake was found at 35 degree C and 15% inoculum size represented the maximum Cs uptake. After 72 hour incubation period, maximum Cs uptake was recorded. Generally, Bacillus licheniformis removed more than 80% of Co and 50% of Cs from the broth medium. Addition of clay to Bacillus licheniformis increased both Co or Cs uptake. Bacillus licheniformis was gamma resistant and 10 KGy reduced the viability by 5.3 log cycles. The irradiated and non-irradiated cultures can grow on 500 or 700 mg Co or Cs. Bacillus licheniformis removed 99.32% of the Co radionuclides and 99.28% of Cs radionuclides

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

Science.gov (United States)

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

2017-05-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

NARCIS (Netherlands)

Mattijsen, F.; Georgiadi, A.; Andasarie, T.; Szalowska, E.; Zota, A.; Krones-Herzig, A.; Kersten, A.H.

2014-01-01

Peroxisome proliferator-activated receptors (PPARs) play major roles in the regulation of hepatic lipid metabolism through the control of numerous genes involved in processes such as lipid uptake and fatty acid oxidation. Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a

Placental expression of asialoglycoprotein receptor associated with Hepatitis B virus transmission from mother to child.

Science.gov (United States)

Vyas, Ashish Kumar; Ramakrishna, Usha; Sen, Bijoya; Islam, Mojahidul; Ramakrishna, Gayatri; Patra, Sharda; Rastogi, Archana; Sarin, Shiv Kumar; Trehanpati, Nirupma

2018-04-30

Asialoglycoprotein receptor expression on hepatocytes has been associated with endocytosis, binding and uptake of hepatitis B virus. The role of asialoglycoprotein receptor in hepatitis B virus vertical transmission and its expression on placenta has not yet been studied. Thirty-four HBsAg+ve and 13 healthy pregnant mothers along with their newborns were enrolled. The former were categorized into transmitting and non-transmitting mothers based on their newborns being hepatitis B surface antigen and hepatitis B virus DNA positive. Expression of asialoglycoprotein receptor and hepatitis B surface antigen in placenta and isoform of asialoglycoprotein receptor on dendritic cell in peripheral and cord blood dendritic cells were analysed using flowcytometry, immune histochemistry, immune florescence and qRT-PCR. Twelve HBsAg+ve mothers transmitted hepatitis B virus to their newborns whereas the rest (n = 22) did not. Hepatitis B virus-transmitting mothers showed increased expression of asialoglycoprotein receptor in trophoblasts of placenta. Immunofluorescence microscopy revealed colocalization of hepatitis B surface antigen and asialoglycoprotein receptor in placenta as well as in DCs of transmitting mothers. There was no significant difference in the expression of asialoglycoprotein receptor on peripheral blood mononuclear cells or chord blood mononuclear cells between the 2 groups. However, hepatitis B virus-transmitting mothers and their HBsAg+ve newborns showed increased mRNA levels of isoform of asialoglycoprotein receptor on dendritic cell in peripheral blood mononuclear cells. Hepatitis B virus-transmitting mothers and their HBsAg+ve newborns showed an increased expression of isoform of asialoglycoprotein receptor on dendritic cell on circulating dendritic cells compared to hepatitis B virus non-transmitting mothers and their negative newborns. This study revealed that increased expression of asialoglycoprotein receptor in placenta and colocalization with

Hepatic artery embolization for treatment of patients with hereditary hemorrhagic telangiectasia and symptomatic hepatic vascular malformations

Energy Technology Data Exchange (ETDEWEB)

Chavan, Ajay [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Klinikum Oldenburg, Department of Radiology and Nuclear Medicine, Oldenburg (Germany); Caselitz, Martin; Wagner, Siegfried; Manns, Michael [Hannover Medical School, Department of Gastroenterology and Hepatology, Hannover (Germany); Gratz, Karl-Friedrich [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Lotz, Joachim; Kirchhoff, Timm; Galanski, Michael [Hannover Medical School, Department of Diagnostic Radiology, Hannover (Germany); Piso, Plinio [Hannover Medical School, Department of Abdominal and Transplantation Surgery, Hannover (Germany)

2004-11-01

At present there is no established therapy for treating patients with hereditary hemorrhagic telangiectasia (HHT) and symptomatic hepatic involvement. We present the results of a prospective study with 15 consecutive patients who were treated with staged hepatic artery embolization (HAE). Branches of the hepatic artery were selectively catheterized and embolized in stages using polyvinyl alcohol particles (PVA) and platinum microcoils or steel macrocoils. Prophylactic antibiotics, analgesics and anti-emetics were administered after every embolization. Clinical symptomatology and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 28 months; range 10-136 months). Five patients had abdominal pain and four patients had symptoms of portal hypertension. The cardiac output was raised in all patients, with cardiac failure being present in 11 patients. After treatment, pain resolved in all five patients, and portal hypertension improved in two of the four patients. The mean cardiac output decreased significantly (P<0.001) from 12.57{+-}3.27 l/min pre-treatment to 8.36{+-}2.60 l/min at the end of follow-up. Symptoms arising from cardiac failure resolved or improved markedly in all but one patient. Cholangitis and/or cholecystitis occurred in three patients of whom two required a cholecystectomy. One patient with pre-existent hepatic cirrhosis died as a complication of the procedure. Staged HAE yields long-term relief of clinical symptoms in patients with HHT and hepatic involvement. Patients with pre-existing hepatic cirrhosis may be poor candidates for HAE. (orig.)

Improving access to health care for chronic hepatitis B among migrant Chinese populations: A systematic mixed methods review of barriers and enablers.

Science.gov (United States)

Vedio, A; Liu, E Z H; Lee, A C K; Salway, S

2017-07-01

Migrant Chinese populations in Western countries have a high prevalence of chronic hepatitis B but often experience poor access to health care and late diagnosis. This systematic review aimed to identify obstacles and supports to timely and appropriate health service use among these populations. Systematic searches resulted in 48 relevant studies published between 1996 and 2015. Data extraction and synthesis were informed by models of healthcare access that highlight the interplay of patient, provider and health system factors. There was strong consistent evidence of low levels of knowledge among patients and community members; but interventions that were primarily focused on increasing knowledge had only modest positive effects on testing and/or vaccination. There was strong consistent evidence that Chinese migrants tend to misunderstand the need for health care for hepatitis B and have low satisfaction with services. Stigma was consistently associated with hepatitis B, and there was weak but consistent evidence of stigma acting as a barrier to care. However, available evidence on the effects of providing culturally appropriate services for hepatitis B on increasing uptake is limited. There was strong consistent evidence that health professionals miss opportunities for testing and vaccination. Practitioner education interventions may be important, but evidence of effectiveness is limited. A simple prompt in patient records for primary care physicians improved the uptake of testing, and a dedicated service increased targeted vaccination coverage for newborns. Further development and more rigorous evaluation of more holistic approaches that address patient, provider and system obstacles are needed. © 2017 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Silicon improves salt tolerance by increasing root water uptake in Cucumis sativus L.

Science.gov (United States)

Zhu, Yong-Xing; Xu, Xuan-Bin; Hu, Yan-Hong; Han, Wei-Hua; Yin, Jun-Liang; Li, Huan-Li; Gong, Hai-Jun

2015-09-01

Silicon enhances root water uptake in salt-stressed cucumber plants through up-regulating aquaporin gene expression. Osmotic adjustment is a genotype-dependent mechanism for silicon-enhanced water uptake in plants. Silicon can alleviate salt stress in plants. However, the mechanism is still not fully understood, and the possible role of silicon in alleviating salt-induced osmotic stress and the underlying mechanism still remain to be investigated. In this study, the effects of silicon (0.3 mM) on Na accumulation, water uptake, and transport were investigated in two cucumber (Cucumis sativus L.) cultivars ('JinYou 1' and 'JinChun 5') under salt stress (75 mM NaCl). Salt stress inhibited the plant growth and photosynthesis and decreased leaf transpiration and water content, while added silicon ameliorated these negative effects. Silicon addition only slightly decreased the shoot Na levels per dry weight in 'JinYou 1' but not in 'JinChun 5' after 10 days of stress. Silicon addition reduced stress-induced decreases in root hydraulic conductivity and/or leaf-specific conductivity. Expressions of main plasma membrane aquaporin genes in roots were increased by added silicon, and the involvement of aquaporins in water uptake was supported by application of aquaporin inhibitor and restorative. Besides, silicon application decreased the root xylem osmotic potential and increased root soluble sugar levels in 'JinYou 1.' Our results suggest that silicon can improve salt tolerance of cucumber plants through enhancing root water uptake, and silicon-mediated up-regulation of aquaporin gene expression may in part contribute to the increase in water uptake. In addition, osmotic adjustment may be a genotype-dependent mechanism for silicon-enhanced water uptake in plants.

Assessment of hepatic functional reserve for hepatic resection using {sup 99m}Tc-PMT scintigraphy in comparison with {sup 99m}Tc-GSA scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Sakuma, Atsushi [Dokkyo Univ. School of Medicine, Mibu, Tochigi (Japan)

2000-03-01

{sup 99m}Tc-diethylenetriamine-pentaacetic acid-galactosyl human serum albumin({sup 99m}Tc-GSA) scintigraphy has been reported as a useful study of hepatic functional reserve recently. We have performed {sup 99m}Tc-N-pyridoxyl-5-methyl-tryptophan({sup 99m}Tc-PMT) and {sup 99m}Tc-GSA preoperatively for evaluation of hepatic functional reserve and compared the usefulness of those scintigraphy study. Twenty-four patients who were the candidates of hepatic resection underwent {sup 99m}Tc-PMT scintigraphy preoperatively. Hepatic blood flow coefficient (K value), the amount of hepatic blood flow (HBF), and the ratio of portal blood flow (PVR) were computed. {sup 99m}Tc-GSA scintigraphy was also performed within two weeks of the {sup 99m}Tc-PMT scintigraphy, and the ratio of disappearance (HH{sub 15}) and the hepatic uptake ratio (LHL{sub 15}) were computed. The relationship between K value, HBF, PVR, HH{sub 15} and LHL{sub 15} was analyzed. Their correlation with other liver function tests was also examined. K value and HBF did not show statistically significant correlations with HH{sub 15} and LHL{sub 15}, PVR correlated statistically significantly HH{sub 15} and LHL{sub 15}. K value correlated with the preoperative values of cholinesterase, Fischer ratio, {gamma}-globulin, ICGR{sub 15}, albumin, and platelet count. There was a statistically significant correlation between LHL{sub 15} and the value of cholinesterase, {gamma}-globulin, platelet count, and Fischer ratio. When the liver resection of subsegmentectomy or more was indicated in 10 patients, nine patients had LHL{sub 15} value less than 0.9 which delineated possibility of poor prognosis. However, judging from K value and HBF, liver resection was considered feasible and it was all successfully performed, resulting in good prognosis. From this study, it is suspected that {sup 99m}Tc-GSA scintigraphy reflect the severity of liver fibrosis and the amount of portal blood flows, and {sup 99m}Tc-PMT scintigraphy

Occult hepatitis B among Iranian hepatitis C patients

Directory of Open Access Journals (Sweden)

Ahmad shavakhi

2009-02-01

Full Text Available

• BACKGROUND: Occult hepatitis B is defined as presence of HBV DNA in tissue or serum without hepatitis B surface antigen. The aim of this study is to determine frequency of occult hepatitis B among hepatitis C patients in Tehran and compare the route of transmission and liver enzymes between positive and negative HBV DNA patients.
• METHODS: In a cross sectional study, serum of 103 hepatitis C cases (79.6% men and 20.4% women were analyzed for s, x and core genes via a nested polymerase chain reaction technique.
• RESULTS: HBV DNA was detectable in serum of 20 patients (19.4%. No significant difference in age, sex and route of transmission were seen in HBV DNA positive and negative patients. In HBV DNA positive and negative groups, mean of AST was 73, 47 (p < 0.05 and mean of ALT was 76 and 36 respectively (p < 0.05.
• CONCLUSION: Occult hepatitis B was observed in a considerable number of hepatitis C patients in Tehran. It was associated with elevation in liver enzyme but was not related to route of transmission.
• KEY WORD: Occult hepatitis B, hepatitis C, cirrhosis.

Hepatic artery infusion (HAI) for hepatic metastases in combination with hepatic resection and hepatic radiation

International Nuclear Information System (INIS)

Merrick, H.W.; Dobelbower, R.R.; Ringleint, J.F.; Skeel, R.T.

1986-01-01

Renewed interest in hepatic artery infusion has been stimulated by the development of a totally implantable pump which eliminates many of the problems encountered by the external pumps and catheters. As the potential benefit of hepatic artery infusion would be greater if either all gross disease were removed by prior resection, or alternatively, if non-resectable disease were irradiated in conjunction with hepatic artery infusion, the authors initiated a phase I-II trial to evaluate combined modality therapy

The Hepatitis C treatment experience: Patients' perceptions of the facilitators of and barriers to uptake, adherence and completion.

Science.gov (United States)

Sublette, Victoria A; Smith, Sian K; George, Jacob; McCaffery, Kirsten; Douglas, Mark W

2015-01-01

This study explores the perceptions of patients receiving treatment for Hepatitis C to determine what factors influence their decision to commence treatment, ability to maintain adherence and complete their treatment program. Semi-structured interview techniques were used in a qualitative study of 20 patients undergoing treatment for Chronic Hepatitis C (CHC). To explore patients' perceived barriers and facilitators of Hepatitis C treatment adherence and completion. Analysis of patient interviews identified four key themes: (1) motivations for commencing CHC treatment - fear of death and ridding themselves of stigma and shame; (2) the influential role of provider communication - patients reported that information and feedback that was personalised to their needs and lifestyles was the most effective for improving adherence to treatment; (3) facilitators of treatment adherence and completion - social, emotional and practical support improved adherence and completion, as did temporarily ceasing employment; (4) barriers to treatment adherence and completion - these included side effects, stigma, a complicated dosing schedule and limitations of the public healthcare system. To increase treatment adherence and completion rates, a patient-centred approach is required that addresses patients' social, practical, and emotional support needs and adaptive coping strategies.

Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

DEFF Research Database (Denmark)

Inturi, Swetha; Wang, Guankui; Chen, Fangfang

2015-01-01

demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...... by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human...... leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement...