Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver.

PubMed

de Leede, Eleonora M; Burgmans, Mark C; Martini, Christian H; Tijl, Fred G J; van Erkel, Arian R; Vuyk, Jaap; Kapiteijn, Ellen; Verhoef, Cornelis; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

2016-07-31

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this.

PubMed

He, Ju-Xiu; Ohno, Kenji; Tang, Jun; Hattori, Masao; Tani, Tadato; Akao, Teruaki

2014-11-01

To investigate the influence of co-administrated Da-Chaihu-Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions. A single dose of DCT was administered with nifedipine simultaneously, 2 h before, 30 min before or 30 min after nifedipine administration. Pharmacokinetics of nifedipine with or without DCT were compared. The influences of DCT on nifedipine intestinal mucosal and hepatic metabolism were studied by using rat in-vitro everted jejunal sac model and hepatic microsomes. A simultaneous co-administration of DCT significantly increased the area under concentration-time curve from time zero to infinity (AUC0-inf ) of nifedipine. In-vitro mechanism investigations revealed that DCT inhibited both the intestinal and the hepatic metabolism of nifedipine. Further study on the optimal dosing interval for nifedipine and DCT revealed that administration of DCT 30 min before or after nifedipine did not significantly change the AUC of nifedipine. The bioavailability of nifedipine is significantly increased by a simultaneous oral co-administration of DCT. This increase is caused by the inhibitory effect of DCT on both the intestinal mucosal and the hepatic metabolism of nifedipine. The dose interval between DCT and nifedipine needs to be set for over 30 min to avoid such drug-drug interactions. © 2014 Royal Pharmaceutical Society.

Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient.

PubMed

van Dommelen, Laura; Verbon, Annelies; van Doorn, H Rogier; Goossens, Valère J

2010-03-01

We present a case of a clinical manifest hepatitis B virus infection and a potentially misleading HBV serological profile in an HIV-1 positive patient despite previous HBV vaccination. The patient presented with an acute hepatitis B and there was no indication of chronic HBV infection or the presence of a mutation in the 'a' determinant. Remarkably, simultaneously with high HBV surface antigen and HBV viral load, high anti-HBs antibodies were present. If, due to previous HBV vaccination only anti-HBs was tested in this patient, the result of the high anti-HBs antibodies could be very misleading and offering a false sense of security. Our findings contribute to the ongoing discussion on how to assess HBV specific immunological memory and determining the role of HBV booster vaccinations in immunocompromised individuals.

Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

PubMed

Hope, Thomas A; Pampaloni, Miguel Hernandez; Nakakura, Eric; VanBrocklin, Henry; Slater, James; Jivan, Salma; Aparici, Carina Mari; Yee, Judy; Bergsland, Emily

2015-08-01

To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct: a case report.

PubMed

Budzynska, Agnieszka; Hartleb, Marek; Nowakowska-Dulawa, Ewa; Krol, Robert; Remiszewski, Piotr; Mazurkiewicz, Michal

2014-04-14

Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.

PubMed

Kusumoto, Shigeru; Tanaka, Yasuhito; Suzuki, Ritsuro; Watanabe, Takashi; Nakata, Masanobu; Takasaki, Hirotaka; Fukushima, Noriyasu; Fukushima, Takuya; Moriuchi, Yukiyoshi; Itoh, Kuniaki; Nosaka, Kisato; Choi, Ilseung; Sawa, Masashi; Okamoto, Rumiko; Tsujimura, Hideki; Uchida, Toshiki; Suzuki, Sachiko; Okamoto, Masataka; Takahashi, Tsutomu; Sugiura, Isamu; Onishi, Yasushi; Kohri, Mika; Yoshida, Shinichiro; Sakai, Rika; Kojima, Minoru; Takahashi, Hiroyuki; Tomita, Akihiro; Maruyama, Dai; Atsuta, Yoshiko; Tanaka, Eiji; Suzuki, Takayo; Kinoshita, Tomohiro; Ogura, Michinori; Mizokami, Masashi; Ueda, Ryuzo

2015-09-01

There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quantitation of hepatitis B virus DNA in plasma using a sensitive cost-effective "in-house" real-time PCR assay.

PubMed

Daniel, Hubert Darius J; Fletcher, John G; Chandy, George M; Abraham, Priya

2009-01-01

Sensitive nucleic acid testing for the detection and accurate quantitation of hepatitis B virus (HBV) is necessary to reduce transmission through blood and blood products and for monitoring patients on antiviral therapy. The aim of this study is to standardize an "in-house" real-time HBV polymerase chain reaction (PCR) for accurate quantitation and screening of HBV. The "in-house" real-time assay was compared with a commercial assay using 30 chronically infected individuals and 70 blood donors who are negative for hepatitis B surface antigen, hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody. Further, 30 HBV-genotyped samples were tested to evaluate the "in-house" assay's capacity to detect genotypes prevalent among individuals attending this tertiary care hospital. The lower limit of detection of this "in-house" HBV real-time PCR was assessed against the WHO international standard and found to be 50 IU/mL. The interassay and intra-assay coefficient of variation (CV) of this "in-house" assay ranged from 1.4% to 9.4% and 0.0% to 2.3%, respectively. Virus loads as estimated with this "in-house" HBV real-time assay correlated well with the commercial artus HBV RG PCR assay ( r = 0.95, P < 0.0001). This assay can be used for the detection and accurate quantitation of HBV viral loads in plasma samples. This assay can be employed for the screening of blood donations and can potentially be adapted to a multiplex format for simultaneous detection of HBV, HIV and HCV to reduce the cost of testing in blood banks.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

77 FR 15761 - Office of the Assistant Secretary for Health, Statement of Organization, Functions, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... hepatitis, other infectious diseases of public health significance, and blood safety and availability. The..., including viral hepatitis and HIV/AIDS, across HHS and monitors progress toward achieving established goals... to promote effective prevention and advancement of research for HIV/AIDS, viral hepatitis, and other...

Multimodal brain monitoring in fulminant hepatic failure

PubMed Central

Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

2016-01-01

Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

Combined branched-DNA and conventional HBV PCR assays for detection of serum HBV-DNA in hepatitis B e antigen-positive chronic hepatitis B patients.

PubMed

Ozdarendeli, Aykut; Toroman, Zulal Asci; Bulut, Yasemin; Demirbag, Kutbeddin; Kalkan, Ahmet; Ozden, Mehmet; Kilic, Suleyman Sirri

2006-01-01

Monitoring of HBV replication level is very useful for the management of patients with chronic HBV. However, the use of the correct tools to quantify HBV-DNA levels in serum and monitor the replication of HBV is of paramount importance in terms of diagnosis, and antiviral treatment of patients with chronic HBV infection. The aim of this study was to combine the bDNA assay and HBV PCR to improve detection of viremia the patients with HBeAg-positive chronic hepatitis B infection. In this study, 67 HBeAg-positive chronic hepatitis B patients were analyzed to determine viremia level using bDNA and HBV PCR assays. Sixty-four patients with HBeAg-positive chronic hepatitis B showed positivity by conventional HBV PCR, whereas 56 subjects with HBeAg-positive chronic hepatitis B showed HBV-DNA levels by bDNA. The results indicated that it is reasonable to use the bDNA assay to determine HBV replicative activity first, and use conventional HBV-PCR for HBeAg-positive chronic hepatitis B patient samples that are negative in bDNA assay.

Amelioration of L-thyroxine-induced hyperthyroidism by coumarin (1,2-benzopyrone) in female rats.

PubMed

Panda, Sunanda; Kar, Anand

2007-11-01

1. The efficacy of coumarin (1,2-benzopyrone) was examined for the regulation of hyperthyroidism in female rats. 2. Coumarin was administered (10 mg/kg per day for 15 days) to l-thyroxine (L-T(4))-induced hyperthyroid as well as to euthyroid rats and changes in serum concentrations of thyroid hormones and in associated parameters, such as serum cholesterol, activity of hepatic 5'-monodeiodinase (5'DI) and glucose-6-phosphatase (G-6-Pase), glycogen content, bodyweight and daily food consumption, were analysed. Simultaneously, changes in hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also investigated. 3. Although L-T(4) administration increased serum levels of thyroid hormones, the activity of hepatic 5'DI, G-6-Pase and LPO and daily food consumption, it decreased the level of serum cholesterol, hepatic glycogen content and the activities of anti-oxidant enzymes, such as SOD, CAT and GSH. 4. However, simultaneous administration of coumarin for 15 days to a group of hyperthyroid animals reversed most of the aforementioned changes, indicating its potential to ameliorate hyperthyroidism. Moreover, the drug did not increase, but rather decreased, hepatic LPO, suggesting its safe nature. 5. The present findings reveal a positive role for coumarin in the regulation of hyperthyroidism without any hepatotoxicity. It also appears that the test compound inhibits thyroid function at both a glandular level and at the level of peripheral conversion of T(4) to tri-iodothyronine.

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

PubMed

Takada, Hideaki; Kobayashi, Takashi; Ogawa, Kohei; Miyata, Hitomi; Sawada, Atsuro; Akamatsu, Shusuke; Negoro, Hiromitsu; Saito, Ryoichi; Terada, Naoki; Yamasaki, Toshinari; Inoue, Takahiro; Teramoto, Yuki; Shibuya, Shinsuke; Haga, Hironori; Kaido, Toshimi; Uemoto, Shinji; Ogawa, Osamu

2017-08-01

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

A new strategy to improve the cost-effectiveness of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis testing of blood donations in sub-Saharan Africa: a pilot study in Burkina Faso.

PubMed

Kania, Dramane; Sangaré, Lassana; Sakandé, Jean; Koanda, Abdoulaye; Nébié, Yacouba Kompingnin; Zerbo, Oumarou; Combasséré, Alain Wilfried; Guissou, Innocent Pierre; Rouet, François

2009-10-01

In Africa where blood-borne agents are highly prevalent, cheaper and feasible alternative strategies for blood donations testing are specifically required. From May to August 2002, 500 blood donations from Burkina Faso were tested for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), syphilis, and hepatitis C virus (HCV) according to two distinct strategies. The first strategy was a conventional simultaneous screening of these four blood-borne infectious agents on each blood donation by using single-marker assays. The second strategy was a sequential screening starting by HBsAg. HBsAg-nonreactive blood donations were then further tested for HIV. If nonreactive, they were further tested for syphilis. If nonreactive, they were finally assessed for HCV antibodies. The accuracy and cost-effectiveness of the two strategies were compared. By using the simultaneous strategy, the seroprevalences of HBsAg, HIV, syphilis, and HCV among blood donors in Ouagadougou were estimated to be 19.2, 9.8, 1.6, and 5.2%. No significant difference of HIV, syphilis, and HCV prevalence rates was observed by using the sequential strategy (9.2, 1.9, and 4.7%, respectively). Whatever the strategy used, 157 blood donations (31.4%) were found to be reactive for at least one transfusion-transmissible agent and were thus discarded. The sequential strategy allowed a cost decrease of euro 908.6, compared to the simultaneous strategy. Given that approximately there are 50,000 blood donations annually in Burkina Faso, the money savings reached potentially euro 90,860. In resource-limited settings, the implementation of a sequential strategy appears as a pragmatic solution to promote safe blood supply and ensure sustainability of the system.

Pharmacokinetic and pharmacodynamic interaction between nifedipine and metformin in rats: competitive inhibition for metabolism of nifedipine and metformin by each other via CYP isozymes.

PubMed

Choi, Young H; Lee, Myung G

2012-05-01

It has been reported that hypertension exponentially increases in the patients with type 2 diabetes mellitus. Thus, this study was performed to investigate the pharmacokinetic and pharmacodynamic interactions between nifedipine and metformin, since both drugs were commonly metabolized via hepatic CYP2C and 3A subfamilies in rats. Nifedipine (3 mg/kg) and metformin (100 mg/kg) were simultaneously administered intravenously or orally to rats. Concentrations (I) of each drug in the liver and intestine, maximum velocity (V(max)), Michaelis-Menten constant (K(m)), and intrinsic clearance (CL(int)) for the disappearance of each drug, apparent inhibition constant (K(i)) and [I]/K(i) ratios of each drug in liver and intestine were determined. Also the metabolism of each drug in rat and human CYPs and blood pressure were also measured. After the simultaneous single intravenous administration of both drugs together, the AUCs of each drug were significantly greater than that in each drug alone due to the competitive inhibition for the metabolism of nifedipine by metformin via hepatic CYP3A1/2 and of metformin by nifedipine via hepatic CYP2C6 and 3A1/2. After the simultaneous single oral administration of both drugs, the significantly greater AUCs of each drug than that in each drug alone could have mainly been due to the competitive inhibition for the metabolism of nifedipine and metformin by each other via intestinal CYP3A1/2 in addition to competitive inhibition for the hepatic metabolism of each drug as same as the intravenous study.

Using ultrasonography to monitor liver blood flow for liver transplant from donors supported on extracorporeal membrane oxygenation.

PubMed

Zhu, Xian-Sheng; Wang, Sha-Sha; Cheng, Qi; Ye, Chuang-Wen; Huo, Feng; Li, Peng

2016-02-01

Extracorporeal membrane oxygenation (ECMO) has been used to support brain-dead donors for liver procurement. This study investigated the potential role of ultrasonographic monitoring of hepatic perfusion as an aid to improve the viability of liver transplants obtained from brain-dead donors who are supported on ECMO. A total of 40 brain-dead patients maintained on ECMO served as the study population. Hepatic blood flow was monitored using ultrasonography, and perioperative optimal perfusion was maintained by calibrating ECMO. Liver function tests were performed to assess the viability of the graft. The hepatic arterial blood flow was well maintained with no significant changes observed before and after ECMO (206 ± 32 versus 241 ± 45 mL/minute; P = 0.06). Similarly, the portal venous blood flow was also maintained throughout (451 ± 65 versus 482 ± 77 mL/minute; P = 0.09). No significant change in levels of total bilirubin, alanine transaminase, and lactic acid were reported during ECMO (P = 0.17, P = 0.08, and P = 0.09, respectively). Before the liver is procured, ultrasonographic monitoring of hepatic blood flow could be a valuable aid to improve the viability of a liver transplant by allowing for real-time calibration of ECMO perfusion in brain-dead liver donors. In our study, ultrasonographic monitoring helped prevent warm ischemic injury to the liver graft by avoiding both overperfusion and underperfusion of the liver. © 2015 American Association for the Study of Liver Diseases.

Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers

PubMed Central

Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

2017-01-01

Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators. PMID:29246882

Hep-CORE: a cross-sectional study of the viral hepatitis policy environment reported by patient groups in 25 European countries in 2016 and 2017.

PubMed

Lazarus, Jeffrey V; Stumo, Samya R; Harris, Magdalena; Hendrickx, Greet; Hetherington, Kristina L; Maticic, Mojca; Jauffret-Roustide, Marie; Tallada, Joan; Simojoki, Kaarlo; Reic, Tatjana; Safreed-Harmon, Kelly

2018-04-01

The first World Health Organization (WHO) global health sector strategy on hepatitis B and C viruses (HBV and HCV) has called for the elimination of viral hepatitis as a major public health threat by 2030. This study assesses policies and programmes in support of elimination efforts as reported by patient groups in Europe. In 2016 and 2017, hepatitis patient groups in 25 European countries participated in a cross-sectional survey about their countries' policy responses to HBV and HCV. The English-language survey addressed overall national response; public awareness/engagement; disease monitoring; prevention; testing/diagnosis; clinical assessment; and treatment. We performed a descriptive analysis of data and compared 2016 and 2017 findings. In 2017, 72% and 52% of the 25 European study countries were reported to not have national HBV and HCV strategies respectively. The number of respondents indicating that their governments collaborated with civil society on viral hepatitis control increased from 13 in 2016 to 18 in 2017. In both 2016 and 2017, patient groups reported that 9 countries (36%) have disease registers for HBV and 11 (44%) have disease registers for HCV. The number of countries reported to have needle and syringe exchange programmes available in all parts of the country dropped from 10 (40%) in 2016 to 8 in 2017 (32%). In both 2016 and 2017, patient groups in 5 countries (20%) reported that HCV treatment is available in non-hospital settings. From 2016 to 2017, the reported number of countries with no restrictions on access to direct-acting antivirals for HCV increased from 3 (12%) to 7 (28%), and 5 fewer countries were reported to refuse treatment to people who are currently injecting drugs. The patient-led Hep-CORE study offers a unique perspective on the readiness of study countries to undertake comprehensive viral hepatitis elimination efforts. Viral hepatitis monitoring should be expanded to address policy issues more comprehensively and to incorporate civil society perspectives, as is the case with global HIV monitoring. Policy components should also be explicitly added to the WHO framework for monitoring country-level progress against viral hepatitis. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Key outcomes and addressing remaining challenges--perspectives from a final evaluation of the China GAVI project.

PubMed

Yang, Weizhong; Liang, Xiaofeng; Cui, Fuqiang; Li, Li; Hadler, Stephen C; Hutin, Yvan J; Kane, Mark; Wang, Yu

2013-12-27

During the China GAVI project, implemented between 2002 and 2010, more than 25 million children received hepatitis B vaccine with the support of project, and the vaccine proved to be safe and effective. With careful consideration for project savings, China and GAVI continually adjusted the budget, additionally allowing the project to spend operational funds to support demonstration projects to improve timely birth dose (TBD), conduct training of EPI staff, and to monitor the project impact. Results from the final evaluation indicated the achievement of key outcomes. As a result of government co-investment, human resources at county level engaged in hepatitis B vaccination increased from 29 per county on average in 2002 to 66 in 2009. All project counties funded by the GAVI project use auto-disable syringes for hepatitis B vaccination and other vaccines. Surveyed hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009 among infants. The HBsAg prevalence declined from 9.67% in 1992 to 0.96% in 2006 among children under 5 years of age. However, several important issues remain: (1) China still accounts for the largest annual number of perinatal HBV infections (estimated 84,121) in the WHO WPR region; (2) China still lacks a clear national policy for safe injection of vaccines; (3) vaccination of high risk adults and protection of health care workers are still not implemented; (4) hepatitis B surveillance needs to be refined to more accurately monitor acute hepatitis B; and (5) a program for treatment of persons with chronic HBV infection is needed. Recommendations for future hepatitis B control include: using the lessons learned from the China GAVI project for future introductions of new vaccines; addressing unmet needs with a second generation hepatitis B program to reach every infant, including screening mothers, and providing HBIG for infants born to HBsAg positive mothers; expanding vaccination to high risk adults; addressing remaining unsafe injection issues; and improving monitoring of acute hepatitis B. This paper describes findings and discusses perspectives from a final project evaluation, a national stratified validated cross-sectional survey done in October 2010. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electromyographic monitoring for prevention of phrenic nerve palsy in second-generation cryoballoon procedures.

PubMed

Franceschi, Frédéric; Koutbi, Linda; Gitenay, Edouard; Hourdain, Jérome; Maille, Baptiste; Trévisan, Lory; Deharo, Jean-Claude

2015-04-01

Electromyography-guided phrenic nerve (PN) monitoring using a catheter positioned in a hepatic vein can aid in preventing phrenic nerve palsy (PNP) during cryoballoon ablation for atrial fibrillation. We wanted to evaluate the feasibility and efficacy of PN monitoring during procedures using second-generation cryoballoons. This study included 140 patients (43 women) in whom pulmonary vein isolation was performed using a second-generation cryoballoon. Electromyography-guided PN monitoring was performed by pacing the right PN at 60 per minute and recording diaphragmatic compound motor action potential (CMAP) via a quadripolar catheter positioned in a hepatic vein. If a 30% decrease in CMAP amplitude was observed, cryoapplication was discontinued with forced deflation to avoid a PNP. Monitoring was unfeasible in 8 of 140 patients (5.7%), PNP occurred in 1. Stable CMAP amplitudes were achieved before ablation in 132 of 140 patients (94.3%). In 18 of 132 patients (13.6%), a 30% decrease in CMAP amplitude occurred and cryoablation was discontinued. Each time, recovery of CMAP amplitude took <60 s. In 9 of 18 cases, a second cryoapplication in the same pulmonary vein was safely performed. We observed no PNP or complication related to electromyography-guided PN monitoring. Electromyography-guided PN monitoring using a catheter positioned in a hepatic vein seems feasible and effective to prevent PNP during cryoballoon ablation using second-generation cryoballoon. © 2015 American Heart Association, Inc.

Prevalence of hepatitis B virus subgenotypes and basal core promoter, precore variants in patients with acute hepatitis B in central Vietnam.

PubMed

Hayashi, Kazuhiko; Katano, Yoshiaki; Chuong, Tran Xuan; Takeda, Yasushi; Ishigami, Masatoshi; Itoh, Akihiro; Hirooka, Yoshiki; Nakano, Isao; Huy, Tran Van; Minh, Nguyen Ngoc; Diem, Tran thi Minh; An, Dong thi Hoai; Phiet, Pham Hoang; Goto, Hidemi

2009-01-01

Hepatitis B virus (HBV) has been classified into 8 genotypes that have different geographic distributions. The clinical outcomes of acute hepatitis are dependent on genotype. The aim of this study was to investigate the distribution of HBV subgenotypes and basal core promoter (BCP)/precore (PC) regions in acute hepatitis patients in Central Vietnam to clarify the distributions and the clinical and virological differences. 27 patients with acute hepatitis B were studied. HBV subgenotypes and BCP/PC variants were determined by direct sequencing of the preS, BCP/PC regions, respectively. HBV subgenotypes B4/Ba (n = 22) and C1/Cs (n = 5) were detected. Of the 27 patients, 3 developed fulminant hepatic failure, and all were infected with B4/Ba. Three patients had a BCP mutation, and 10 patients had a PC mutation in subgenotype B4/Ba. Three patients with C1/Cs had a BCP mutation. Two of 3 patients who progressed to fulminant hepatic failure had T1762, A1764, and A1896 simultaneously. None of the patients with acute, self-limited hepatitis carried these triple mutations. The prevalent HBV subgenotypes in patients with acute hepatitis B in Central Vietnam were B4/Ba and C1/Cs. BCP/PC variants have an association with the development of fulminant hepatic failure in subgenotype B4/Ba. Copyright 2009 S. Karger AG, Basel.

Effect of genotypes on the quantification of hepatitis C virus (HCV) RNA in clinical samples using the Amplicor HCV Monitor Test and the Quantiplex HCV RNA 2.0 assay (bDNA).

PubMed

Tong, C Y; Hollingsworth, R C; Williams, H; Irving, W L; Gilmore, I T

1998-07-01

The Amplicor HCV Monitor test and the Quantiplex HCV RNA 2.0 (bDNA) assay are two commercially available assays for the quantification of hepatitis C virus (HCV) RNA in clinical samples. A direct comparison of the two assays was carried out using sera frozen previously from patients known to be chronically infected with HCV. Overall, 61 samples from 51 patients were tested simultaneously by the two methods: 67% (28/42) of the patients were infected by HCV genotype/serotype 1, 10% (4/42) with type 2, and 24% (10/42) with type 3. When the absolute value from each assay was examined, the Quantiplex assay gave a consistently higher reading and the mean logarithmic difference between the two assays was 1.4 (1.0 in type 1, 2.0 in type 2, and 2.2 in type 3). When analyzed according to genotype, strong correlation was observed between the two assays for type 1 (r = 0.83, 95% CI 0.63-0.93, P < 0.01), but not for nontype 1 samples. Despite the difference in absolute level reported by the two assays, there was a consistent trend of change in HCV RNA concentration by both assays in patients whose consecutive samples were analyzed and the differences between the two assays in consecutive samples were within 0.4 log of each other. The results suggested that with samples containing genotype 1, the Amplicor assay was more sensitive than the Quantiplex assay by about one log. However, the sensitivities of the two assays with nontype 1 samples were much closer probably due to the failure of the Amplicor assay to quantify nontype 1 genotypes effectively.

Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia-reperfusion injury.

PubMed

Li, Tzu-Hao; Liu, Chih-Wei; Lee, Pei-Chang; Huang, Chia-Chang; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Yang, Ying-Ying; Hsieh, Shie-Liang; Lin, Han-Chieh; Tsai, Chang-Youh

2017-07-01

For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization. Toll-like receptor 4-activated KCs can release proinflammatory mediators, skew M1 polarization and escalate liver IR injury. Decoy receptor 3 (DcR 3 ) could be potential agents simultaneously blocking the IR liver injury-related pathogenic changes and extend the survival of steatotic graft. Rats were fed with methionine and choline-deficient high-fat diet (MCD HFD) for 6 weeks to induce HS. Preliminary experiments with HS group and IR group were conducted, and either immunoglobulin G Fc protein or DcR3 analogue was treated for 14 days in all groups to evaluate the severity. In the Zucker rat-focused experiments, various serum and hepatic substances, M1 polarization, and hepatic microcirculation were assessed. We found that serum/hepatic DcR 3 levels were lower in nonalcoholic fatty liver disease patients with HS. DcR 3 a protected Zucker rats with HS from IR liver injury. The beneficial effects of DcR 3 a supplement were mediated by inhibiting hepatic M1 polarization of KCs, decreasing serum/hepatic TNFα, nitric oxide, nitrotyrosine, soluble TNF-like cytokine 1A, Fas ligand, and interferon-γ levels, neutrophil infiltration, and improving hepatic microcirculatory failure among rats with IR-injured steatotic livers. Additionally, downregulated hepatic TNF-like cytokine 1A/Fas-ligand and toll-like receptor 4/nuclear factor-κB signals were found to mediate the DcR 3 a-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR 3 a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes. Copyright © 2017. Published by Elsevier Taiwan LLC.

Traumatic common hepatic artery injury causing isolated right hepatic ischemia due to a left accessory artery. A case report.

PubMed

Fernandes, Eduardo; Pedrazzani, Corrado; Gerena, Marielia; Omi, Ellen

2017-01-01

Hepatic arterial liver flow is renowned for its redundancy. Previous studies have demonstrated that the common hepatic artery is not essential for liver survival. We present a case of a 31year-old involved in a high-speed motor vehicle accident whose liver survived thanks to the presence of an accessory hepatic artery. We present the case of a 31year-old male who sustained a traumatic injury of the proper hepatic artery following a motor vehicle accident. The patient suffered temporary right liver lobe ischemia due to the presence of an accessory left hepatic artery. This resulted in the selective formation of 'biliary lakes' distinctively within the territory of the right hepatic artery supply. Simultaneously the patient developed a pseudo-aneurysm of the proper hepatic artery which required radiology intervention. At the time of pseudo-aneurysm embolisation, a rich network of arterial collaterals had formed between the accessory left hepatic and the inferior phrenic artery. On follow up the biliary lakes to the right lobe had resolved, but a small area at the periphery of the right lobe had encountered atrophy. This case report is an 'in vivo' demonstration of liver resilience to arterial flow re-distribution and demonstrates the ability of the biliary epithelium to recover from and ischemic injury. Parenchymal liver survival is mostly independent from flow within the common hepatic artery. Acute and chronic liver parenchyma changes following interruption of hepatic artery flow can still occur. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Risk Management of HBV Reactivation: Construction of Check System].

PubMed

Tanaka, Yasuhito

2015-09-01

In recent years, reactivation of HBV in patients receiving cancer chemotherapy or immunosuppressive therapy has been a problem. Generally, HBV-DNA levels are elevated prior to HBsAg concentration, and then hepatic dysfunction is observed in the process of hepatitis by HBV reactivation. Therefore, the monitoring of HBV-DNA is useful for the prediction of hepatic dysfunction, and nucleoside/nucleoside analogue (NA) administration is able to prevent this HBV reactivation. According to these facts, "Guidelines for the Prevention of HBV Reactivation in Patients Receiving Immunosuppressive Therapy or Chemotherapy", 2009 (revised as "JSH Guidelines for the Management of Hepatitis B Virus Infection", 2013) is established, and the diagnostic algorithm of HBsAg, anti-HBc, anti-HBs, and HBV-DNA has relevant descriptions. Combination therapy with rituximab and steroid for malignant lymphoma has a high risk of leading to fulminant hepatitis and, consequently, the guidelines are widely followed in such cases. We introduced the improvement of electronic medical recording and ordering systems in collaboration with hepatologists, and such a system has been widely used. Although the monitoring of HBV-DNA levels is required every 1-3 months, the guidelines are not followed strictly in cases such as rheumatoid disease and solid tumors only with chemotherapy or steroid treatment. Since a DNA assay is complicated and expensive, cost-effective, time-saving, and highly sensitive/specific measurements are required as well. Therefore, Lumipulse HBsAg-HQ (CLIA method) with high sensitivity is expected to be used for the monitoring of HBV reactivation.

Comparative evaluation of hepatitis C virus RNA quantitation by branched DNA, NASBA, and monitor assays.

PubMed

Lunel, F; Cresta, P; Vitour, D; Payan, C; Dumont, B; Frangeul, L; Reboul, D; Brault, C; Piette, J C; Huraux, J M

1999-02-01

Several studies have shown a relationship between pretreatment hepatitis C virus (HCV) viral load and the response to interferon (IFN) therapy, creating a need for quantitative HCV-RNA assays. Here, we compared three commercial methods: nucleic acid sequence-based amplification NASBA (Organon), branched DNA 2.0 (bDNA) (Chiron), and Monitor (Roche), with reverse-transcription polymerase chain reaction (RT-PCR) as the reference. We assessed sensitivity and reproducibility on a well-characterized panel of sera (EUROHEP), a Chimp Rodney plasma pool, and samples from IFN-treated and -untreated patients with chronic hepatitis C caused by different HCV genotypes. The reproducibility of the NASBA and bDNA methods was slightly better than that of Monitor, especially for genotypes 2 and 4. NASBA had the highest sensitivity (99% vs. 94% and 88% with Monitor and bDNA, respectively), especially for the follow-up of patients on IFN. NASBA gave the highest HCV-RNA concentrations, which were approximately 10-fold more than with the bDNA assay and 100-fold more than with the Monitor kit. The linearity, tested on the chimp Rodney plasma pool, was better with bDNA for high viral load than with NASBA and Monitor, although for low concentration of HCV RNA, bDNA was negative. Pretreatment viral load was lower in patients who had a sustained virological response to IFN, although the bDNA method was not sensitive enough to quantify all pretreatment samples. This study indicates that gene amplification methods (NASBA or Monitor) have better sensitivity than bDNA assays for quantification of HCV RNA in patients with chronic HCV infection, although the bDNA and NASBA methods are more likely to quantify all genotypes. Prospective studies are needed to demonstrate the usefulness of quantitative assays for the follow-up of patients with chronic hepatitis C.

Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: The dalcetrapib experience

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

Hoflack, J-C.; Mueller, L., E-mail: Lutz.Mueller@roche.com; Fowler, S.

2012-03-15

Introduction: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. Methods: Liver samplesmore » were obtained from ∼ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. Results: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5–1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day). Discussion: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay. -- Highlights: ► Liver tumors were induced in male mice by dalcetrapib in a 2-y study (bioassay). ► Cyp2b10 induction typifies activation of nuclear receptor CAR in mouse liver. ► First report of hepatic Cyp2b10 monitoring at the end of a mouse bioassay. ► Cyp2b10 induction supports CAR activation by dalcetrapib in mouse bioassay. ► CAR activation is a mechanism of hepatic tumorigenesis of no relevance to humans.« less

Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers.

PubMed

Hutin, Yvan; Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

2017-12-15

Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators. ©Yvan Hutin, Daniel Low-Beer, Isabel Bergeri, Sarah Hess, Jesus Maria Garcia-Calleja, Chika Hayashi, Antons Mozalevskis, Annemarie Rinder Stengaard, Keith Sabin, Hande Harmanci, Marc Bulterys. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 15.12.2017.

Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis.

PubMed

Li, Xiaoyan; Su, Yujie; Hua, Xuefeng; Xie, Chan; Liu, Jing; Huang, Yuehua; Zhou, Liang; Zhang, Min; Li, Xu; Gao, Zhiliang

2017-04-11

Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University. Liver tissues at least 3 cm away from the tumor site were used for the analyses. Levels of Th17 cells and regulatory T cells were detected by flow cytometry analysis and immunohistochemistry. In vitro experiment, we adopted magnetic cell sorting to investigate how hepatic stellate cells regulate the levels of Th17 cells and regulatory T cells. We found that hepatic Th17 cells and regulatory T cells were increased in patients with advanced stage HBV-related liver fibrosis. Hepatic stellate cells upregulated the levels of Th17 cells and regulatory T cells via PGE2/EP2 and EP4 pathway. We found that the increased levels of Th17 cells and regulatory T cells were upregulated by hepatic stellate cells. These results may provide insight into the role of hepatic stellate cells and Th17 cells and regulatory T cells in the persistence of fibrosis and into the occurrence of hepatocellular carcinoma following cirrhosis.

Process of hepatic metastasis from pancreatic cancer: biology with clinical significance.

PubMed

Shi, Haojun; Li, Ji; Fu, Deliang

2016-06-01

Pancreatic cancer shows a remarkable preference for the liver to establish secondary tumors. Selective metastasis to the liver is attributed to the development of potential microenvironment for the survival of pancreatic cancer cells. This review aims to provide a full understanding of the hepatic metastatic process from circulating pancreatic cancer cells to their settlement in the liver, serving as a basic theory for efficient prediction and treatment of metastatic diseases. A systematic search of relevant original articles and reviews was performed on PubMed, EMBASE and Cochrane Library for the purpose of this review. Three interrelated phases are delineated as the contributions of the interaction between pancreatic cancer cells and the liver to hepatic metastasis process. Chemotaxis of disseminated pancreatic cancer cells and simultaneous defensive formation of platelets or neutrophils facilitate specific metastasis toward the liver. Remodeling of extracellular matrix and stromal cells in hepatic lobules and angiogenesis induced by proangiogenic factors support the survival and growth of clinical micrometastasis colonizing the liver. The bimodal role of the immune system or prevalence of cancer cells over the immune system makes metastatic progression successfully proceed from micrometastasis to macrometastasis. Pancreatic cancer is an appropriate research object of cancer metastasis representing more than a straight cascade. If any of the successive or simultaneous phases, especially tumor-induced immunosuppression, is totally disrupted, hepatic metastasis will be temporarily under control or even cancelled forever. To shrink cancers on multiple fronts and prolong survival for patients, novel oral or intravenous anti-cancer agents covering one or different phases of metastatic pancreatic cancer are expected to be integrated into innovative strategies on the premise of safety and efficacious biostability.

Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.

PubMed

Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Fujimoto, Yuki; Furuie, Sumie; Yamamura, Ken-Ichi; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Moriyama, Mitsuaki; Sinasac, David S; Yamamoto, Takashi; Furukawa, Tatsuhiko; Kobayashi, Keiko

2017-04-01

Mice carrying simultaneous homozygous mutations in the genes encoding citrin, the mitochondrial aspartate-glutamate carrier 2 (AGC2) protein, and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD), are a phenotypically representative model of human citrin (a.k.a., AGC2) deficiency. In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. The double-KO mice showed clear suppressed intake of sucrose, consuming less with progressively higher concentrations compared to the other mice. Similar observations were made when glycerol or ethanol were given. The preference of Ctrn-KO and mGPD-KO mice varied with the different treatments; essentially no differences were observed for sucrose, while an intermediate intake or similar to that of the double-KO mice was observed for glycerol and ethanol. We next examined the hepatic glycerol 3-phosphate, citrate, citrulline, lysine, glutamate and adenine nucleotide levels following forced enteral administration of these solutions. A strong correlation between the simultaneous increased hepatic glycerol 3-phosphate and decreased ATP or total adenine nucleotide content and observed aversion of the mice during evaluation of their voluntary preferences was found. Overall, our results suggest that the aversion observed in the double-KO mice to these solutions is initiated and/or mediated by hepatic metabolic perturbations, resulting in a behavioral response to increased hepatic cytosolic NADH and a decreased cellular adenine nucleotide pool. These findings may underlie the dietary predilections observed in human citrin deficient patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

PubMed Central

PERNOLLET, M; JOUVIN-MARCHE, E; LEROY, V; VIGAN, I; ZARSKI, J -P; MARCHE, P N

2002-01-01

Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56− conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3−CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Vα24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56− T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0·715, P < 0·0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56− lymphocytes and both Knodell score (r = 0·624, P = 0·003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56− conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations: PMID:12452844

The future of viral hepatitis testing: innovations in testing technologies and approaches.

PubMed

Peeling, Rosanna W; Boeras, Debrah I; Marinucci, Francesco; Easterbrook, Philippa

2017-11-01

A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most people with hepatitis remain unaware of their infection. Advances in rapid detection technology have created new opportunities for enhancing access to testing and care, as well as monitoring of treatment. This article examines a range of other technological innovations that can be leveraged to provide more affordable and simplified approaches to testing for HBV and HCV infection and monitoring of treatment response. These include improved access to testing through alternative sampling methods (use of dried blood spots, oral fluids, self-testing) and combination rapid diagnostic tests for detection of HIV, HBV and HCV infection; more affordable options for confirmation of virological infection (HBV DNA and HCV RNA) such as point-of-care molecular assays, HCV core antigen and multi-disease polyvalent molecular platforms that make use of existing centralised laboratory based or decentralised TB and HIV instrumentation for viral hepatitis testing; and finally health system improvements such as integration of laboratory services for procurement and sample transportation and enhanced data connectivity to support quality assurance and supply chain management.

Reversible severe hepatitis in anorexia nervosa: a case report and overview.

PubMed

Ramsoekh, Dewkoemar; Taimr, Pavel; Vanwolleghem, Thomas

2014-04-01

Mildly elevated transaminases are often observed in anorexia nervosa patients, but severe hepatitis is less common. We suggest that hypoperfusion is the pathogenetic factor that causes severe hepatitis in a patient with a very poor nutritional status and present an overview of previous case reports. In our patient, early initiation of intravenous fluids resulted in rapid recovery of the liver test abnormalities, despite minimal oral caloric intake, the refusal of enteral feeding and the development of a hypoglycemic coma. Two months after admission, transaminases had normalized. Reversible severe hepatitis has been described in most of the cases, with only one anorexia nervosa-related fatal hepatitis. In general, both adequate hydration and gradual enteral feeding with monitoring of electrolytes are essential in the management of anorexia patients with severe hepatitis.

Feasibility of reaching world health organization targets for hepatitis C and the cost-effectiveness of alternative strategies.

PubMed

Wisløff, T; White, R; Dalgard, O; Amundsen, E J; Meijerink, H; Kløvstad, H

2018-04-06

New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed 2 different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy (OST), a clean needle and syringe programme and a combination of both. The most cost-effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduces the incidence of hepatitis C by 2030 by 63% compared with the current incidence. The 2 harm reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase in the current clean needles and syringe programme with OST was clearly the most cost-effective option. This strategy would reduce the incidence of hepatitis C by 80% compared with the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost-effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives. © 2018 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

PubMed

van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

2009-12-15

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

PubMed

Press, A T; Butans, M J; Haider, T P; Weber, C; Neugebauer, S; Kiehntopf, M; Schubert, U S; Clemens, M G; Bauer, M; Kortgen, A

2017-11-13

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Web-based Distributed Medical Information System for Chronic Viral Hepatitis

NASA Astrophysics Data System (ADS)

Yang, Ying; Qin, Tuan-fa; Jiang, Jian-ning; Lu, Hui; Ma, Zong-e.; Meng, Hong-chang

2008-11-01

To make a long-term dynamic monitoring to the chronically ill, especially patients of HBV A, we build a distributed Medical Information System for Chronic Viral Hepatitis (MISCHV). The Web-based system architecture and its function are described, and the extensive application and important role are also presented.

Dietary proanthocyanidins boost hepatic NAD(+) metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats.

PubMed

Aragonès, Gerard; Suárez, Manuel; Ardid-Ruiz, Andrea; Vinaixa, Maria; Rodríguez, Miguel A; Correig, Xavier; Arola, Lluís; Bladé, Cinta

2016-04-22

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD(+)) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD(+) precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD(+). Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD(+) availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD(+) levels.

Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

PubMed Central

Aragonès, Gerard; Suárez, Manuel; Ardid-Ruiz, Andrea; Vinaixa, Maria; Rodríguez, Miguel A.; Correig, Xavier; Arola, Lluís; Bladé, Cinta

2016-01-01

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD+. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD+ levels. PMID:27102823

One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with special reference to biliary image reconstruction.

PubMed

Enkhbold, Ch; Shimada, M; Utsunomiya, T; Ishibashi, H; Yamada, S; Kanamoto, M; Arakawa, Y; Ikemoto, Z; Morine, E; Imura, S

2013-01-01

Three-dimensional CT has become an essential tool for successful hepatic surgery. Up to now, efforts have been made to simultaneously visualize hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone. A 3D-reconstruction of hepatic vasculature was made using data from contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts from axial 2D image, and then reconstructed the 3D image. Both hepatic vasculature and bile duct images were integrated into a single image and it was compared with the 3D image, utilized with MRCP or DIC-CT. The first branches of both the right and left hepatic ducts were hand-traced and visualized for all 100 cases. The second branches of these ducts were visualized in 69 cases, and only the right second branch was recognized in 52 cases. Anomalous variations of bile ducts, such as posterior branch joining into common hepatic duct, were recognized in 12 cases. These biliary tract variations were all confirmed by MRCP or DIC-CT. Our new one-stop shop approach using the 3D imaging technique might contribute to successful hepatectomy as well as reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.

HEPATIC VITAMIN A IN THE RAT AS AFFECTED BY THE ADMINISTRATION OF DIBENZANTHRACENE

PubMed Central

Abels, Jules C.; Gorham, Alice T.; Eberlin, Shirley L.; Halter, Robert; Rhoads, C. P.

1942-01-01

1. The decreased concentrations of vitamin A in the livers of rats given dibenzanthracene probably are due to a particular effect of the carcinogen on the ability of the liver to store the vitamin and not to the production of general hepatic dysfunction. 2. The administration of dibenzanthracene to normal rats does not (a) increase significantly their hepatic content of total fat nor decrease that of phospholipid; (b) impair the ability of their livers to fabricate serum albumin; (c) impair the capacity of their livers to esterify cholesterol or phenol; (d) interfere with the hepatic synthesis and conjugation of glucuronic acid; or (e) interfere with the hepatic storage of riboflavin. 3. The simultaneous ingestion of yeast by the dibenzanthracene-treated rats further depletes their hepatic stores of vitamin A. This depletion conceivably is due to the fact that yeast alone also might deplete the liver of its vitamin A and thus a summation of two similar effects is attained. 4. The results suggest a competition between vitamin A and dibenzanthracene for some substance, possibly a protein, to which vitamin A may be bound in the liver. PMID:19871225

Advances in hepatitis immunization (A, B, E): public health policy and novel vaccine delivery.

PubMed

Hendrickx, Greet; Vorsters, Alex; Van Damme, Pierre

2012-10-01

This review offers an update on hepatitis A, B and E vaccines based on relevant literature published in 2011-2012. Hepatitis A and B vaccines have been commercially available for years; however, the development of the hepatitis E vaccine is still facing some challenges. Current scientific evidence shows that both hepatitis A and B vaccines confer long-term protection. These data supported the updated recommendations from the WHO on hepatitis A and B vaccines and the respective booster policy. In addition, a single-dose hepatitis A vaccination programme may be an option for some intermediate endemic countries, as far as the epidemiological situation is further monitored. Recent data illustrate the co-administration of hepatitis A with infant vaccines, as well as the interchangeability with other hepatitis A vaccines. Two genetically engineered hepatitis E vaccines are currently in development, showing more than 95% protective efficacy. Follow-up of vaccinated individuals confirms the long-term protection offered by the hepatitis A as well as hepatitis B vaccines. Data confirm the safety and immunogenicity profile of both vaccines, also when used in patient groups. The first data on the hepatitis E vaccine look promising, but questions on cross-protection, long-term efficacy and safety and immunogenicity in pregnant women and children less than 2 years remain unanswered.

[Latest Treatment of Viral Hepatitis--Overcoming Hepatitis C and Reactivation of Hepatitis B].

PubMed

Tanaka, Yasuhito

2016-02-01

Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors. These new therapies can eradicate HCV and prevent HCC development. On the other hand, it is difficult to eradicate HBV completely. Although HBV infection can be prevented by vaccination, reactivation of HBV following anti-cancer chemotherapy and immunosuppressive therapy is a well-known complication. HBV reactivation has been reported to be associated with anti-CD20 monoclonal antibody rituximab-containing chemotherapy and TNF-α inhibitor-containing immunosuppressive therapy in HBV-resolved patients. Our prospective observational study revealed that monthly monitoring of HBV DNA was useful for preventing HBV reactivation-related hepatitis among B-cell non-Hodgkin lymphoma patients with resolved HBV infection following rituximab-steroid-chemo, suggesting that preemptive therapy guided by serial HBV DNA monitoring should be recommended. Recently, highly sensitive HBsAg detection by Lumipulse HBsAg-HQ may be useful for several clinical applications. The sensitivity of this assay (5 mIU/mL) was approximately 10-fold higher than Abbott ARCHITECT, but still lower than HBV-DNA assays. The convenient HBsAg-HQ may be useful for detecting occult HBV infection and HBV reactivation in relatively low-risk groups except for those receiving rituximab-steroid-chemo. [

Hepatitis A in Puglia (South Italy) after 10 years of universal vaccination: need for strict monitoring and catch-up vaccination

PubMed Central

2012-01-01

Background Raw seafood consumption was identified as the major risk factor for hepatitis A during the large epidemic of 1996 and 1997 in Puglia (South Italy). In Puglia, vaccination for toddlers and preadolescents has been recommended since 1998. The aim of the study was to evaluate the incidence, seroprevalence, molecular epidemiology, and environmental circulation of hepatitis A virus (HAV) in Puglia more than ten years after the introduction of anti-HAV vaccination in the regional immunization program. Methods Data on the incidence of acute hepatitis A in Puglia were analyzed. Characteristics and risk factors of 97 acute hepatitis A cases occurring in 2008–2009 were analyzed. Serum samples from 868 individuals aged 0 to 40 years were tested for anti-HAV antibodies. Fecal samples from 49 hepatitis A cases were analyzed by sequence analysis in the VP1/P2A region. In 2008, 203 mussel samples and 202 water samples from artesian wells were tested for HAV-RNA. Results Between 1998 and 2009, the incidence of acute hepatitis A declined from 14.8 to 0.8 per 100,000. The most frequent risk factors reported by cases in 2008–2009 were shellfish consumption (85%) and travel outside of Puglia or Italy (26%). Seroepidemiologic survey revealed high susceptibility to HAV in children and adults up to age 30 (65%-70%). None of the mussel or water samples were HAV-positive. Phylogenetic analysis revealed co-circulation of subtypes IA (74%) and IB (26%) and clustering of strains with strains from Germany and France, and those previously circulating in Puglia. Conclusion Vaccination and improved sanitation reduced the incidence of hepatitis A. Strict monitoring and improved vaccination coverage are needed to prevent disease resurgence. PMID:23098290

Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.

PubMed

Georgiou, Leonidas; Penny, Jeffrey; Nicholls, Glynis; Woodhouse, Neil; Blé, François-Xavier; Hubbard Cristinacce, Penny L; Naish, Josephine H

2017-02-01

The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions.

Acute hepatitis after amiodarone infusion.

PubMed

Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

2015-10-16

Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients.

Perioperative Hemodynamic Monitoring of Common Hepatic Artery for Endovascular Embolization of a Pancreaticoduodenal Arcade Aneurysm with Celiac Stenosis

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

Shibata, Eisuke, E-mail: eisuke.shibata1130@gmail.com; Takao, Hidemasa; Amemiya, Shiori

This report describes perioperative hemodynamic monitoring of the common hepatic artery (CHA) during endovascular treatment of a pancreaticoduodenal arcade aneurysm, in a patient with celiac artery stenosis caused by the median arcuate ligament. Pressure monitoring was performed as a safety measure against critical complications such as liver ischemia. As the aneurysm was located in the anterior pancreaticoduodenal artery (APDA) and the posterior pancreaticoduodenal artery (PPDA) was small in caliber, the patient was considered to be at a high risk of liver ischemia. No significant change in pressure was observed in the CHA on balloon occlusion test in the APDA. Immediatelymore » after embolization, the PPDA enlarged and the pressure in the CHA was well maintained. Pressure monitoring appears to improve patient safety during endovascular treatment of visceral aneurysms.« less

Synchronous occurrence of multiple focal nodular hyperplasia and huge hepatic perivascular epithelioid cells tumor (PEComa) in young woman after oral contraceptive use--is there a common pathogenesis?

PubMed

Durczyński, Adam; Hogendorf, Piotr; Szymański, Dariusz; Sporny, Stanisław; Strzelczyk, Janusz

2012-09-01

The association of focal nodular hyperplasia (FNH) and various neoplasms was described, but coincidence of multiple FNH and hepatic perivascular epithelioid cells tumor (PEComa) has not been reported. The clinical debate of oral contraceptive (OC) influence on FNH growth is ongoing, but no evidence exists about association of hepatic PEComa with OC use. Herein, we report a case of two FNH lesions and huge (150x100x80 mm) left hepatic lobe PEComa that occurred simultaneously in 18-year-old female with previous two year history of OC use, who underwent left hemihepatectomy and right hepatic FNH enucleation. Up to date, the patient has been followed-up for 65 months and remained disease-free. FNH and PEComa have a common vascular cytogenetic denominator. Our case raising a question of a causal relationship of FNH and PEComa with OC use that might be attributed to vascular changes. Future researches of larger sample sizes should further address this issue.

Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases.

PubMed

Kamei, S; Ohkubo, A; Yamanaka, M

1979-08-15

Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases.

Controlling hepatitis C in Rwanda: a framework for a national response.

PubMed

Mbituyumuremyi, Aimable; Van Nuil, Jennifer Ilo; Umuhire, Jeanne; Mugabo, Jules; Mwumvaneza, Mutagoma; Makuza, Jean Damascene; Umutesi, Justine; Nsanzimana, Sabin; Gupta, Neil

2018-01-01

With the introduction of direct-acting antiviral drugs, treatment of hepatitis C is both highly effective and tolerable. Access to treatment for patients, however, remains limited in low- and middle-income countries due to the lack of supportive health infrastructure and the high cost of treatment. Poorer countries are being encouraged by international bodies to organize public health responses that would facilitate the roll-out of care and treatment on a national scale. Yet few countries have documented formal plans and policies. Here, we outline the approach taken in Rwanda to a public health framework for hepatitis C control and care within the World Health Organization hepatitis health sector strategy. This includes the development and implementation of policies and programmes, prevention efforts, screening capacity, treatment services and strategic information systems. We highlight key successes by the national programme for the control and management of hepatitis C: establishment of national governance and planning; development of diagnostic capacity; approval and introduction of direct-acting antiviral treatments; training of key personnel; generation of political will and leadership; and fostering of key strategic partnerships. Existing challenges and next steps for the programme include developing a detailed monitoring and evaluation framework and tools for monitoring of viral hepatitis. The government needs to further decentralize care and integrate hepatitis C management into routine clinical services to provide better access to diagnosis and treatment for patients. Introducing rapid diagnostic tests to public health-care facilities would help to increase case-finding. Increased public and private financing is essential to support care and treatment services.

Soldier-Based Assessment of a Dual-Row Tactor Display during Simultaneous Navigational and Robot-Monitoring Tasks

DTIC Science & Technology

2015-08-01

Navigational and Robot -Monitoring Tasks by Gina Pomranky-Hartnett, Linda R Elliott, Bruce JP Mortimer, Greg R Mort, Rodger A Pettitt, and Gary A...Tactor Display during Simultaneous Navigational and Robot -Monitoring Tasks by Gina Pomranky-Hartnett, Linda R Elliott, and Rodger A Pettitt...2014–31 March 2015 4. TITLE AND SUBTITLE Soldier-Based Assessment of a Dual-Row Tactor Display during Simultaneous Navigational and Robot -Monitoring

Assessment of Spontaneous Fluctuations of Viral Load in Untreated Patients with Chronic Hepatitis C by Two Standardized Quantitation Methods: Branched DNA and Amplicor Monitor

PubMed Central

Halfon, Philippe; Bourlière, Marc; Halimi, Gilles; Khiri, Hacène; Bertezene, Patrice; Portal, Isabelle; Botta-Fridlund, Danielle; Gauthier, André Pierre; Jullien, Monique; Feryn, Jean Marc; Gerolami, Victoria; Cartouzou, Guy

1998-01-01

Quantitation of hepatitis C virus (HCV) RNA in serum has been used to predict and monitor the efficacy of interferon therapy in chronic HCV infection. We prospectively studied the fluctuation of viremia by a longitudinal follow-up of HCV RNA levels for 2 months in six untreated patients. Spontaneous fluctuations of HCV RNA ranged from 2.8- to 5.7-fold with branched DNA assay and from 2.9- to 5.6-fold with Monitor. These large spontaneous fluctuations (up to 0.75 log), observed daily, weekly, and monthly, raise doubt about the clinical value of a single assessment of pretherapeutic viremia. PMID:9650965

Transmission of hepatitis C virus between hemodialysis patients sharing the same machine.

PubMed

Sartor, Catherine; Brunet, Philippe; Simon, Sophie; Tamalet, Catherine; Berland, Yvon; Drancourt, Michel

2004-07-01

After a patient acquired hepatitis C virus (HCV) infection in our unit, we performed epidemiologic and virologic investigations, including genotyping and phylogenetic analyses. The results provided evidence for HCV transmission between two patients sharing the same machine and suggested possible transmission via accidental contamination of the venous pressure monitoring system.

Notes from the field: deaths from acute hepatitis B virus infection associated with assisted blood glucose monitoring in an assisted-living facility--North Carolina, August-October 2010.

PubMed

2011-02-18

Sharing of blood glucose monitoring equipment in assisted-living facilities has resulted in at least 16 outbreaks of hepatitis B virus (HBV) infection in the United States since 2004. On October 12, 2010, the North Carolina Division of Public Health (NCDPH) and the Wayne County Health Department were notified by a local hospital of four residents of a single assisted-living facility with suspected acute HBV infection. NCDPH requested HBV testing of all persons who had resided in the facility during January 1-October 13, 2010, and defined an outbreak-associated case as either 1) positive hepatitis B surface antigen and core immunoglobulin M (IgM) results or 2) clinical evidence of acute hepatitis (jaundice or serum aminotransferase levels twice the upper limit of normal) with onset ≥6 weeks after admission to the facility. Records were reviewed for potential health-care-associated exposures and HBV-related risk factors. Infection control practices were assessed through observations and interviews with facility staff.

The effectiveness of risk communication regarding drug safety information: a nationwide survey by the Japanese public health insurance claims data.

PubMed

Hagiwara, Hiromi; Nakano, Shun; Ogawa, Yoshihiro; Tohkin, Masahiro

2015-06-01

We evaluated the effectiveness of warning letters published by the pharmaceutical regulatory agency in Japan on communication of drug safety and risk by quantitative analysis of the national health insurance claims database (NHICD). We then explored what factors may have affected risk communication. We measured the implementation rate of the hepatitis virus-monitoring test among methotrexate (MTX)-treated patients; a warning letter had been issued regarding the use of MTX, as it apparently activates the hepatitis virus. Data from the NHICD, which include 99·3% of Japanese residents, were used. A total of 4,933,481 patients with rheumatoid arthritis (RA) (January-June, 2010) were the focus of this study. The implementation rate of the hepatitis virus-monitoring test increased from 1·4% before to 1·8% after the warning letter announcement. Logistic regression analysis suggested that the installation of a drug information management room is one of the important factors affecting risk communication. Further analysis revealed that the hepatitis virus monitoring rates in hospitals without drug information management rooms increased from 2·3% to 4·1% due to the issue of the warning letter. The warning letter from the regulatory agency plays an important role in risk communication in hospitals without drug information management rooms. © 2015 John Wiley & Sons Ltd.

Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A Vaccines Among Young Adults: A 3-Year Follow-up Study.

PubMed

Liu, Xue-en; Chen, Hai-ying; Liao, Zheng; Zhou, Yisheng; Wen, Hairong; Peng, Shihui; Liu, Yan; Li, Rui; Li, Jie; Zhuang, Hui

2015-10-15

A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted among adults to evaluate seroprotection rates and geometric mean concentrations of antibody against hepatitis A virus for 36 months. High rates of seroprotection persisted for at least 36 months among adults who received 1 or 2 doses of inactivated hepatitis A vaccine but not among adults who received 1 dose of live attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an effective alternative to a 2-dose schedule. NCT01865968. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Levetiracetam-induced transaminitis in a young male with traumatic brain injury.

PubMed

Rachamallu, Vivekananda; Song, Michael M; Reed, Jace M; Aligeti, Manish

2017-11-01

Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction. Furthermore, monitoring of liver enzymes is often not considered to be critical in levetiracetam therapy. However, hepatotoxicity is still possible with levetiracetam. Here, we report on an 18-year-old male with TBI who developed transaminitis with levetiracetam therapy which resolved following the discontinuation of levetiracetam. A close monitoring of liver enzymes and early recognition of hepatotoxicity is still necessary and critical to preventing major sequelae stemming from levetiracetam-induced hepatotoxicity.

Hepatic fat quantification magnetic resonance for monitoring treatment response in pediatric nonalcoholic steatohepatitis.

PubMed

Koh, Hong; Kim, Seung; Kim, Myung-Joon; Kim, Hyun Gi; Shin, Hyun Joo; Lee, Mi-Jung

2015-09-07

To evaluate the possibility of treatment effect monitoring using hepatic fat quantification magnetic resonance (MR) in pediatric nonalcoholic steatohepatitis (NASH). We retrospectively reviewed the medical records of patients who received educational recommendations and vitamin E for NASH and underwent hepatic fat quantification MR from 2011 to 2013. Hepatic fat fraction (%) was measured using dual- and triple-echo gradient-recalled-echo sequences at 3T. The compliant and non-compliant groups were compared clinically, biochemically, and radiologically. Twenty seven patients (M:F = 24:3; mean age: 12 ± 2.3 years) were included (compliant group = 22, non-compliant = 5). None of the baseline findings differed between the 2 groups, except for triglyceride level (compliant vs non-compliant, 167.7 mg/dL vs 74.2 mg/dL, P = 0.001). In the compliant group, high-density lipoprotein increased and all other parameters decreased after 1-year follow-up. However, there were various changes in the non-compliant group. Dual-echo fat fraction (-19.2% vs 4.6, P < 0.001), triple-echo fat fraction (-13.4% vs 3.5, P < 0.001), alanine aminotransferase (-110.7 IU/L vs -10.6 IU/L, P = 0.047), total cholesterol (-18.1 mg/dL vs 3.8 mg/dL, P = 0.016), and triglyceride levels (-61.3 mg/dL vs 11.2 mg/dL, P = 0.013) were significantly decreased only in the compliant group. The change in body mass index and dual-echo fat fraction showed a positive correlation (ρ = 0.418, P = 0.030). Hepatic fat quantification MR can be a non-invasive, quantitative and useful tool for monitoring treatment effects in pediatric NASH.

Application of k-means clustering algorithm in grouping the DNA sequences of hepatitis B virus (HBV)

NASA Astrophysics Data System (ADS)

Bustamam, A.; Tasman, H.; Yuniarti, N.; Frisca, Mursidah, I.

2017-07-01

Based on WHO data, an estimated of 15 millions people worldwide who are infected with hepatitis B (HBsAg+), which is caused by HBV virus, are also infected by hepatitis D, which is caused by HDV virus. Hepatitis D infection can occur simultaneously with hepatitis B (co infection) or after a person is exposed to chronic hepatitis B (super infection). Since HDV cannot live without HBV, HDV infection is closely related to HBV infection, hence it is very realistic that every effort of prevention against hepatitis B can indirectly prevent hepatitis D. This paper presents clustering of HBV DNA sequences by using k-means clustering algorithm and R programming. Clustering processes are started with collecting HBV DNA sequences from GenBank, then performing extraction HBV DNA sequences using n-mers frequency and furthermore the extraction results are collected as a matrix and normalized using the min-max normalization with interval [0, 1] which will later be used as an input data. The number of clusters is two and the initial centroid selected of the cluster is chosen randomly. In each iteration, the distance of every object to each centroid are calculated using the Euclidean distance and the minimum distance is selected to determine the membership in a cluster until two convergent clusters are created. As the result, the HBV viruses in the first cluster is more virulent than the HBV viruses in the second cluster, so the HBV viruses in the first cluster can potentially evolve with HDV viruses that cause hepatitis D.

Hepatic Dysfunction as a Complication of Combined Valproate and Ketogenic Diet.

PubMed

Stevens, Clare E; Turner, Zahava; Kossoff, Eric H

2016-01-01

The ketogenic diet has long been shown to be an effective therapy for children with medication-refractory seizures. Most complications of the ketogenic diet include short-lived gastrointestinal disturbances, acidosis, and dyslipidemia. Hepatic dysfunction and pancreatitis are among the less common but more serious complications of the ketogenic diet. Many patients on the ketogenic diet receive adjunct treatment with an anticonvulsant drug, and valproate is frequently used. We describe a child who developed hepatic dysfunction in association with the combined use of valproate and the ketogenic diet. After stopping the valproate and then restarting the ketogenic diet, her liver enzymes normalized, and she was able to achieve markedly improved seizure control and quality of life. Although caution should be advised when using both treatments simultaneously, the development of hepatic dysfunction should not preclude continuation of the ketogenic diet, as the hepatotoxic effects may be completely reversed once the valproate is stopped. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative cost effectiveness of varicella, hepatitis A, and pneumococcal conjugate vaccines.

PubMed

Jacobs, R J; Meyerhoff, A S

2001-12-01

Several state and local U.S. governments are considering making varicella, hepatitis A, and/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is confounded by their dissimilar methods. We reviewed U.S. cost-effectiveness studies of childhood varicella, hepatitis A, and pneumococcal conjugate vaccines and identified four providing data required to standardize methods. Vaccination, disease treatment, and work-loss costs were estimated from original study results and current prices. Estimated life-years saved were derived from original study results, epidemiological evidence, and alternative procedures for discounting to present values. Hepatitis A vaccine would have the lowest health system costs per life-year saved. Varicella vaccine would provide the greatest reduction in societal costs, mainly through reduced parent work loss. Pneumococcal conjugate vaccine would cost twice the amount of varicella and hepatitis A vaccines combined and be less cost effective than the other vaccines. Hepatitis A and varicella vaccines, but not pneumococcal conjugate vaccine, meet or exceed conventional standards of cost effectiveness. Copyright 2001 American Health Foundation and Elsevier Science.

Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver.

PubMed

Chukijrungroat, Natsasi; Khamphaya, Tanaporn; Weerachayaphorn, Jittima; Songserm, Thaweesak; Saengsirisuwan, Vitoon

2017-08-01

The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis. Copyright © 2017 the American Physiological Society.

Tip-enhanced fluorescence with radially polarized illumination for monitoring loop-mediated isothermal amplification on Hepatitis C virus cDNA

NASA Astrophysics Data System (ADS)

Wei, Shih-Chung; Chuang, Tsung-Liang; Wang, Da-Shin; Lu, Hui-Hsin; Gu, Frank X.; Sung, Kung-Bin; Lin, Chii-Wann

2015-02-01

A tip nanobiosensor for monitoring DNA replication was presented. The effects of excitation power and polarization on tip-enhanced fluorescence (TEF) were assessed with the tip immersed in fluorescein isothiocyanate solution first. The photon count rose on average fivefold with radially polarized illumination at 50 mW. We then used polymerase-functionalized tips for monitoring loop-mediated isothermal amplification on Hepatitis C virus cDNA. The amplicon-SYBR Green I complex was detected and compared to real-time loop-mediated isothermal amplification. The signals of the reaction using 4 and 0.004 ng/μl templates were detected 10 and 30 min earlier, respectively. The results showed the potential of TEF in developing a nanobiosensor for real-time DNA amplification.

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

PubMed Central

Carrion, Andres F.; Czul, Frank; Arosemena, Leopoldo R.; Selvaggi, Gennaro; Garcia, Monica T.; Tekin, Akin; Tzakis, Andreas G.; Martin, Paul; Ghanta, Ravi K.

2010-01-01

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death. PMID:21234410

Computed tomography of the liver and kidneys in glycogen storage disease.

PubMed

Doppman, J L; Cornblath, M; Dwyer, A J; Adams, A J; Girton, M E; Sidbury, J

1982-02-01

Glycogen, in concentrations encountered in von Gierke's disease, has computed tomography (CT) attenuation coefficients in the 50 to 70 Hounsfield unit (HU: 1,000 scale) range and accounts for the increased density of the liver. However, in eight patients with Type I glycogen storage disease, simultaneous hepatic infiltration with fat and glycogen led to a range of liver CT densities from 13 to 80 HU. Fatty infiltration may facilitate the demonstration of hepatic tumors in older patients with this disease. Half the patients showed increased attenuation coefficients of the renal cortex, indicating glycogen deposition in the kidneys.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Simultaneous Detection of Four Foodborne Viruses in Food Samples Using a One-Step Multiplex Reverse Transcription PCR.

PubMed

Lee, Shin-Young; Kim, Mi-Ju; Kim, Hyun-Joong; Jeong, KwangCheol Casey; Kim, Hae-Yeong

2018-02-28

A one-step multiplex reverse transcription PCR (RT-PCR) method comprising six primer sets (for the detection of norovirus GI and GII, hepatitis A virus, rotavirus, and astrovirus) was developed to simultaneously detect four kinds of pathogenic viruses. The size of the PCR products for norovirus GI and GII, hepatitis A virus (VP3/VP1 and P2A regions), rotavirus, and astrovirus were 330, 164, 244, 198, 629, and 449 bp, respectively. The RT-PCR with the six primer sets showed specificity for the pathogenic viruses. The detection limit of the developed multiplex RT-PCR, as evaluated using serially diluted viral RNAs, was comparable to that of one-step single RT-PCR. Moreover, this multiplex RT-PCR was evaluated using food samples such as water, oysters, lettuce, and vegetable product. These food samples were artificially spiked with the four kinds of viruses in diverse combinations, and the spiked viruses in all food samples were detected successfully.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

PubMed

Dizdar, Omer; Tapan, Umit; Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Barista, Ibrahim

2008-05-01

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

PubMed

Montaudié, H; Sbidian, E; Paul, C; Maza, A; Gallini, A; Aractingi, S; Aubin, F; Bachelez, H; Cribier, B; Joly, P; Jullien, D; Le Maître, M; Misery, L; Richard, M-A; Ortonne, J-P

2011-05-01

To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity. © 2011 The Authors. JEADV © 2011 European Academy of Dermatology and Venereology.

A Public Health Analysis on Gaps in Disease Monitoring and Opportunities for Improved Care for the Management of Hepatitis B and C.

PubMed

Akhtar, Faisal; Rehman, Sabah

2018-01-16

Hepatitis B and Hepatitis C have been major disease-causing agents among humans since they were discovered in the 1960s. Both cause jaundice-like symptoms initially but their prognosis and treatment are somehow different and depend upon many demographic details, such as the age and susceptibility of the patients and any other comorbid conditions. They clinically present primarily with hepatitis and can have many adverse effects or even be life-threatening at times, if not treated properly. However, their epidemiological background and findings in terms of morbidity, mortality, and case fatality rates are different. The disease burden, impact on the healthcare system, and prevention of the two diseases are quite different. The treatment and management options along with the prevention and control measures share unique strategies for handling the two diseases. The purpose of this review is to highlight the gaps in disease monitoring and to find ways and opportunities that can lead to improved care and better management of Hepatitis B and C locally and globally. Online databases were searched and peer-reviewed articles were selected. Key issues identified were lack of education globally in resource-limited settings, leading to a decreased understanding of the potential hazards associated with needle sharing and lack of access to healthcare because of a lack of insurance. The failure of compliance with vaccination leads to an increase in mother-to-child transmission (MTCT)-related infections. Increased global travel demands a systematic program in most immigrant-receiving countries to screen for hepatitis B virus (HBV)/hepatitis c virus (HCV) infections. Delayed U.S. Food and Drug Administration (FDA) licensing for new drugs hampers the treatment of chronic Hepatitis-B (CHB) among children. With the advancement in science, an effective vaccine against HCV will definitely help in eradicating the infection.

Monitoring liver macrophages using nanobodies targeting Vsig4: concanavalin A induced acute hepatitis as paradigm.

PubMed

Zheng, Fang; Devoogdt, Nick; Sparkes, Amanda; Morias, Yannick; Abels, Chloé; Stijlemans, Benoit; Lahoutte, Tony; Muyldermans, Serge; De Baetselier, Patrick; Schoonooghe, Steve; Beschin, Alain; Raes, Geert

2015-02-01

Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation. Copyright © 2014 Elsevier GmbH. All rights reserved.

Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.

PubMed

Goedeke, Leigh; Bates, Jamie; Vatner, Daniel F; Perry, Rachel J; Wang, Ting; Ramirez, Ricardo; Li, Li; Ellis, Matthew W; Zhang, Dongyan; Wong, Kari E; Beysen, Carine; Cline, Gary W; Ray, Adrian S; Shulman, Gerald I

2018-05-23

Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet (HFSD)-induced hepatic steatosis, PKCε activation and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (∼30 to 130%, depending on length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to a ∼15% increase in hepatic VLDL production and ∼20% reduction in triglyceride clearance by lipoprotein lipase (LPL) (P ≤ 0.05). At the molecular level, these changes were associated with increases in LXR/SREBP1 and decreases in PPARα target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

PubMed

Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

2016-02-01

Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. Copyright © 2015 Elsevier B.V. All rights reserved.

Simultaneous non-traumatic perforation of the right hepatic duct and gallbladder: an atypical occurrence.

PubMed

Garg, Pankaj Kumar; Jain, Bhupendra Kumar; Pandey, Satya Deo; Rathi, Vinita; Puri, Amarendra Singh

2012-07-01

Simultaneous non-traumatic perforation of the extrahepatic bile duct and the gallbladder is an uncommon occurrence that has been infrequently reported. We describe a patient with a spontaneous perforation of both the extrahepatic bile duct and the gallbladder. A contrast-enhanced computed tomography (CECT) scan of the abdomen and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a perforation of the gallbladder and a free leak from the right hepatic duct, respectively. Endoscopic biliary drainage following a sphincterotomy and biliary stent placement led to a dramatic improvement in the patient's general condition. He was subsequently scheduled to undergo an elective cholecystectomy. Repeat ERCP performed at 4 weeks after the initial stenting showed a normal cholangiogram and a distally migrated stent, which was there after removed. However, early stent removal led to re-perforation of hepatic duct and gallbladder. A repeat endoscopic biliary drainage did not help, and the patient developed biliary peritonitis. Surgical exploration revealed a perforation at the fundus of the gallbladder, 400 ml of biliopurulent collection and a frozen Calot's triangle. A subtotal cholecystectomy, gall stone removal, and a thorough peritoneal lavage were undertaken. The patient improved postoperatively. The second biliary stent was removed after 4 months. This case report highlights the role of endoscopic biliary drainage in the management of an extrahepatic bile duct perforation and warns against the early removal of a biliary stent.

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis

PubMed Central

Parrón, Ignasi; Planas, Caritat; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Jané, Mireia

2017-01-01

ABSTRACT Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2–98.6) for HAV vaccine and 98.3% (95% CI 91.3–99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases. PMID:27925847

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis.

PubMed

Parrón, Ignasi; Planas, Caritat; Godoy, Pere; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Torner, Nuria; Jané, Mireia; Domínguez, Angela

2017-02-01

Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

Clinical monitoring of intracranial pressure in fulminant hepatic failure.

PubMed

Hanid, M A; Davies, M; Mellon, P J; Silk, D B; Strunin, L; McCabe, J J; Williams, R

1980-10-01

Cerebral oedema is the commonest immediate cause of death in fulminant hepatic failure and an investigation was carried out to determine the value of monitoring intracranial pressure (ICP) and to examine the effects of ICP of dexamethasone therapy and mannitol administration. ICP values in 10 patients at the time of insertion of a subdural pressure transducer (grade IV encephalopathy) averaged 15.5 +/- SD 14.8 mmHg. Despite dexamethansone therapy, which had been started on admission, rises in ICP were subsequently observed in seven of the eight patients who died. In the two patients who survived, the highest reading were 47 and 35 mmHg. Mannitol consistently reversed or arrested ICP rises when pressure was < 60 mmHg. ICP monitoring provides additional information in the managment of patients and is essential if mannitol therapy is to be used.

Transmission of hepatitis B virus among persons undergoing blood glucose monitoring in long-term-care facilities--Mississippi, North Carolina, and Los Angeles County, California, 2003-2004.

PubMed

2005-03-11

Regular monitoring of blood glucose levels is an important component of routine diabetes care. Capillary blood is typically sampled with the use of a fingerstick device and tested with a portable glucometer. Because of outbreaks of hepatitis B virus (HBV) infections associated with glucose monitoring, CDC and the Food and Drug Administration (FDA) have recommended since 1990 that fingerstick devices be restricted to individual use. This report describes three recent outbreaks of HBV infection among residents in long-term-care (LTC) facilities that were attributed to shared devices and other breaks in infection-control practices related to blood glucose monitoring. Findings from these investigations and previous reports suggest that recommendations concerning standard precautions and the reuse of fingerstick devices have not been adhered to or enforced consistently in LTC settings. The findings underscore the need for education, training, adherence to standard precautions, and specific infection-control recommendations targeting diabetes-care procedures in LTC settings.

Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats

PubMed Central

Ferrigno, Andrea; Rizzo, Vittoria; Tarantola, Eleonora

2014-01-01

Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury. PMID:24592193

Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

PubMed

von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

2004-08-12

Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

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.

PubMed

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.

Improving birth dose coverage of hepatitis B vaccine.

PubMed Central

Hipgrave, David B.; Maynard, James E.; Biggs, Beverley-Ann

2006-01-01

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC. PMID:16501717

Hepatitis A Surveillance and Vaccine Use in China From 1990 Through 2007

PubMed Central

Cui, Fuqiang; Hadler, Stephen C; Zheng, Hui; Wang, Fuzhen; Zhenhua, Wu; Yuansheng, Hu; Gong, Xiaohong; Chen, Yuansheng; Liang, Xiaofeng

2009-01-01

Background Hepatitis A vaccines have been highly effective in preventing hepatitis A. To investigate the epidemiology of hepatitis A in China after hepatitis A vaccine became available, we reviewed reported cases of hepatitis A and the use of hepatitis A vaccine in China during the period from 1990 through 2007. Methods Data from the National Notifiable Disease Reporting System from 1990 to 2007 and the Emergency Events Reporting System from 2004 to 2007 were reviewed and epidemiologic characteristics analyzed. Hepatitis A vaccine distribution between 1992 and 2007 was also reviewed. Results The incidence of hepatitis A has declined by 90% since 1990, from 56 to 5.9 per 105/year. Declines in age-specific incidence were seen in all age groups, most dramatically among children younger than 10 years. Disease incidence still varies substantially: poorer western provinces have had the highest incidences since 2000. In high-incidence provinces, children younger than 10 years continue to have a high disease incidence. Only 50% of cases were laboratory-confirmed, and only 3% occurred in reported local outbreaks. Over 156 million doses of hepatitis A vaccine have been distributed since 1992, and use has continued to increase since 2003. Conclusions Incidence of hepatitis A has decreased in all age groups, likely due to changing socioeconomic conditions and increasing hepatitis A vaccine use. Nevertheless, western populations remain at high risk, with transmission predominantly occurring among children. The epidemiology of hepatitis A transmission is not well understood. Improved surveillance with better laboratory confirmation is needed to monitor the impact of universal hepatitis A vaccination of young children; this strategy began to be implemented in 2008. PMID:19561383

[Performance evaluation of Abbott RealTime HBV Quantification Kit for HBV viral load by real-time PCR].

PubMed

Kim, Myeong Hee; Cha, Choong Hwan; An, Dongheui; Choi, Sung Eun; Oh, Heung Bum

2008-04-01

Hepatitis B virus (HBV) DNA quantification is necessary for starting and monitoring of antiviral therapy in patients with chronic hepatitis B. This study was intended to assess the clinical performance of Abbott RealTime HBV Quantification kit (Abbott Laboratories, USA). The performance was evaluated in terms of precision, linearity, detection sensitivity, cross-reactivity, and carry-over. A correlation with the Real-Q HBV Quantification kit (BioSewoom Inc., Korea) was also examined using serum samples from 64 patients diagnosed with chronic hepatitis B and underwent lamivudine therapy in Asan Medical Center. We verified the trueness of the system by comparing the outputs with the assigned values of the BBI panel (BBI Diagnostics, USA). Within-run and between-run coefficients of variation (CV) were 3.56-4.71% and 3.03-4.98%, respectively. Linearity was manifested ranging from 53 to 10(9)copies/mL and the detection sensitivity was verified to be 51 copies/mL. None of hepatitis C virus showed cross-reactivity. No cross-contamination occurred when negative and positive samples were alternatively placed in a row. It showed a good correlation with the Real-Q HBV (r(2)=0.9609) and the test results for the BBI panel were also well agreed to the assigned values (r(2)=0.9933). The performance of Abbott RealTime HBV Quantification kit was excellent; thus, it should be widely used in starting and monitoring of antiviral therapy in Korean patients with chronic hepatitis B.

Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

PubMed Central

Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong

2014-01-01

China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter

PubMed Central

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-01-01

OBJECTIVES: Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. METHODS: In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical–chemical assays. RESULTS: The median age was 56 years (25–78 years); 51.7% were women and median body mass index was 31.9 kg/m2 (22.4–44.8 kg/m2). After 14 days, a significant CAP reduction (14.0% P<0.001) was observed from 295 dB/m (216–400 dB/m) to 266 dB/m (100–353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). CONCLUSIONS: This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover. PMID:27311064

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter.

PubMed

Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-06-16

Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical-chemical assays. The median age was 56 years (25-78 years); 51.7% were women and median body mass index was 31.9 kg/m(2) (22.4-44.8 kg/m(2)). After 14 days, a significant CAP reduction (14.0%; P<0.001) was observed from 295 dB/m (216-400 dB/m) to 266 dB/m (100-353 dB/m). In parallel, body weight decreased by 4.6% (P<0.001), of which 61.9% was body fat. In addition, liver stiffness (P=0.002), γ-GT activities, and serum lipid concentrations decreased (all P<0.001). This study shows for the first time that non-invasive elastography can be used to monitor rapid effects of dietary treatment for hepatic steatosis. CAP improvements occur after only 14 days on short-term low-calorie diet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection.

PubMed

Bonifati, Claudio; Lora, Viviana; Graceffa, Dario; Nosotti, Lorenzo

2016-07-28

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias

PubMed Central

Chirnomas, Sarah Deborah; Geukes-Foppen, Marnix; Barry, Kristen; Braunstein, Jennifer; Kalish, Leslie A.; Neufeld, Ellis J.; Powell, Andrew J.

2017-01-01

This study examined the relationship between hepatic and myocardial iron concentration, assessed by T2*-MRI in 66 patients (3–82 years) with transfusion-dependent anemias and thalassemia intermedia, to determine whether hepatic iron levels alone suffice for chelation adjustments. We found a poor correlation between hepatic and myocardial iron (r = 0.10, P = 0.43) and identified a subgroup (14%) with increased myocardial iron without a matched degree of hepatic hemosiderosis. Left ventricular ejection fraction was insensitive for detecting elevated myocardial iron. These findings were present in both adult and pediatric patients. We recommend therapeutic monitoring of iron burden by evaluation of both liver and myocardial iron with T2*-MRI. PMID:18661491

The evaluation of potential pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers.

PubMed

Tortorici, Michael A; Parks, Virginia; Matschke, Kyle; Korth-Bradley, Joan; Patat, Alain

2013-04-01

Sirolimus and tacrolimus are immunosuppressive compounds that have been used concomitantly in renal transplant patients. Both drugs are dosed orally and have common intestinal and hepatic metabolism and intestinal transport mechanisms. As such, there is a potential for pharmacokinetic drug interaction. A single-dose, open-label, four-period, four-treatment, randomized crossover study was conducted in 27 healthy fasting volunteers. Each subject received a 15-mg oral dose of sirolimus alone, a 10-mg oral dose of tacrolimus alone, sirolimus and tacrolimus administered simultaneously, and tacrolimus administered 4 h before sirolimus. Whole blood and plasma samples for sirolimus and tacrolimus testing were analyzed by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were assessed using noncompartmental methods and were compared using analysis of variance (ANOVA). The geometric mean ratio and 90 % confidence interval (CI) area under the concentration-time curve from time 0 to infinity (AUCinf) for sirolimus administered simultaneously with tacrolimus versus sirolimus alone were 97 and 89-106, respectively, and, when administered in a staggered approach versus sirolimus alone, 107 and 98-117, respectively. The geometric mean ratio (%) and 90 % CI AUCinf for tacrolimus administered simultaneously with sirolimus versus tacrolimus alone were 92 and 82-102, respectively, and, when administered in a staggered approach versus tacrolimus alone, 94 and 84-105, respectively. The results of this study demonstrate a lack of any clinically important drug interaction between sirolimus and tacrolimus in healthy subjects after single-dose administration. However, due to the complexity of anti-rejection immunosuppressive therapy dosing, we suggest that sirolimus and tacrolimus concentration monitoring be performed when changes in dosing are made for either drug regimen.

Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of epidemiological surveillance and time trend analysis.

PubMed

Estripeaut, Dora; Contreras, Rodolfo; Tinajeros, Olga; Castrejón, Maria Mercedes; Shafi, Fakrudeen; Ortega-Barria, Eduardo; DeAntonio, Rodrigo

2015-06-22

In April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix(®)junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama. Hepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000-2006) and after (2008-2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0-14 years) during 2009-2011 at three sentinel hospitals in Panama. Overall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000-2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008-2010) in all age groups. In the hospital-based surveillance (2009-2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1-4 years) but were not vaccinated. Our study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression.

PubMed

Wang, Feng; Liu, Jin-Cheng; Zhou, Rui-Jun; Zhao, Xi; Liu, Mei; Ye, Hua; Xie, Mei-Lin

2017-09-25

Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days. The results showed that in the apigenin-treated mice, the expression of hepatic cytochrome P450 2E1 (CYP2E1) and nuclear factor kappa B proteins as well as contents of hepatic malondialdehyde and tumor necrosis factor-alpha were reduced, while the levels of hepatic reduced glutathione, glutathione reductase, glutathione peroxidase, and glutathione S-transferase were increased, especially in the 300 mg/kg group. A significant change in hepatic steatosis was also observed in the apigenin 300 mg/kg group. Apigenin pretreatment could increase the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 proteins, and decrease the expression of hepatic sterol regulatory element binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase proteins. These findings demonstrated that apigenin might exert a protective effect on alcohol-induced liver injury, and its mechanisms might be related to the regulations of hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

The beneficial effects of combined grape pomace and omija fruit extracts on hyperglycemia, adiposity and hepatic steatosis in db/db mice: a comparison with major index compounds.

PubMed

Cho, Su-Jung; Park, Hae-Jin; Jung, Un Ju; Kim, Hye-Jin; Moon, Byoung Seok; Choi, Myung-Sook

2014-09-30

This study investigated the effects of combined grape pomace and omija fruit extracts (GO) on diabetes-related metabolic changes in type 2 diabetic db/db mice. The effects of GO were compared with those of a resveratrol and schizandrin mixture (RS), which is a mixture of major components of GO. Mice were fed a normal diet with RS (0.005% resveratrol and 0.02% schizandrin in diet, w/w) or GO (0.3% grape pomace ethanol extract and 0.05% omija fruit ethanol extract in diet, w/w) for seven weeks. RS and GO not only lowered the levels of blood and plasma glucose, HbA1c, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) with a simultaneous decrease in hepatic gluconeogenic enzymes activities and adiposity, but also improved preservation of the pancreatic β-cells. Plasma leptin and resistin levels were lower while the plasma adiponectin level was higher in the RS and GO groups than in the control group. Especially, GO increased hepatic glucokinase activity and gene expression and improved hepatic steatosis by elevating fatty acid oxidation compared to RS. These findings suggest that GO ameliorates hyperglycemia, adiposity and hepatic steatosis in type 2 diabetic mice.

Contribution of dietary starch to hepatic and systemic carbohydrate fluxes in European seabass (Dicentrarchus labrax L.).

PubMed

Viegas, Ivan; Rito, João; Jarak, Ivana; Leston, Sara; Caballero-Solares, Albert; Metón, Isidoro; Pardal, Miguel A; Baanante, Isabel V; Jones, John G

2015-05-14

In the present study, the effects of partial substitution of dietary protein by digestible starch on endogenous glucose production were evaluated in European seabass (Dicentrarchus labrax). The fractional contribution of dietary carbohydrates v. gluconeogenesis to blood glucose appearance and hepatic glycogen synthesis was quantified in two groups of seabass fed with a diet containing 30% digestible starch (DS) or without a carbohydrate supplement as the control (CTRL). Measurements were performed by transferring the fish to a tank containing water enriched with 5% (2)H2O over the last six feeding days, and quantifying the incorporation of (2)H into blood glucose and hepatic glycogen by (2)H NMR. For CTRL fish, gluconeogenesis accounted for the majority of circulating glucose while for the DS fish, this contribution was significantly lower (CTRL 85 (SEM 4) % v. DS 54 (SEM 2) %; P < 0.001). Hepatic glycogen synthesis via gluconeogenesis (indirect pathway) was also significantly reduced in the DS fish, in both relative (CTRL 100 (SEM 1) % v. DS 72 (SEM 1) %; P < 0.001) and absolute terms (CTRL 28 (SEM 1) v. DS 17 (sem 1) μmol/kg per h; P < 0.001). A major fraction of the dietary carbohydrates that contributed to blood glucose appearance (33 (sem 1) % of the total 47 (SEM 2) %) had undergone exchange with hepatic glucose 6-phosphate. This indicated the simultaneous activity of hepatic glucokinase and glucose 6-phosphatase. In conclusion, supplementation of digestible starch resulted in a significant reduction of gluconeogenic contributions to systemic glucose appearance and hepatic glycogen synthesis.

Minimally invasive surgery using the open magnetic resonance imaging system combined with video-assisted thoracoscopic surgery for synchronous hepatic and pulmonary metastases from colorectal cancer: report of four cases.

PubMed

Sonoda, Hiromichi; Shimizu, Tomoharu; Takebayashi, Katsushi; Ohta, Hiroyuki; Murakami, Koichiro; Shiomi, Hisanori; Naka, Shigeyuki; Hanaoka, Jun; Tani, Tohru

2015-05-01

Simultaneous resection of hepatic and pulmonary metastases (HPM) from colorectal cancer (CRC) has been reported to be effective, but it is also considered invasive. We report the preliminary results of performing minimally invasive surgery using the open magnetic resonance (MR) imaging system to resect synchronous HPM from CRC in four patients. All four patients were referred for thoracoscopy-assisted interventional MR-guided microwave coagulation therapy (T-IVMR-MCT) combined with video-assisted thoracoscopic surgery (VATS). The median diameters of the HPM were 18.2 and 23.2 mm, respectively. The median duration of VATS and T-IVMR-MCT was 82.5 and 139 min, respectively. All patients were discharged without any major postoperative complications. One patient was still free of disease at 24 months and the others died of disease progression 13, 36, and 47 months without evidence of recurrence in the treated area. Thus, simultaneous VATS + T-IVMR-MCT appears to be an effective option as a minimally invasive treatment for synchronous HPM from CRC.

Direct imaging of the disruption of hepatitis C virus replication complexes by inhibitors of lipid metabolism

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

Lyn, Rodney K.; Department of Chemistry, University of Ottawa, 10 Marie-Curie, Ottawa, K1N 6N5; Kennedy, David C.

2009-11-10

Here we have simultaneously characterized the influence of inhibitors of peroxisome proliferator-activated receptor alpha (PPARalpha) and the mevalonate pathway on hepatocyte lipid metabolism and the subcellular localization of hepatitis C virus (HCV) RNA using two-photon fluorescence (TPF) and coherent anti-Stokes Raman scattering (CARS) microscopy. Using this approach, we demonstrate that modulators of PPARalpha signaling rapidly cause the dispersion of HCV RNA from replication sites and simultaneously induce lipid storage and increases in lipid droplet size. We demonstrate that reductions in the levels of cholesterol resulting from inhibition of the mevalonate pathway upregulates triglyceride levels. We also show that the ratemore » of dispersion of HCV RNA is very rapid when using a PPARalpha antagonist. This occurs with a faster rate to that of direct inhibition of 3-hydroxy-3-methyglutaryl CoA reductase (HMG-CoA reductase) using lovastatin in living cells, demonstrating the potential therapeutic value of modulating host cell pathways as part of a strategy to eliminate chronic HCV infection.« less

Hepatitis C Care in the Department of Veterans Affairs: Building a Foundation for Success.

PubMed

Belperio, Pamela S; Chartier, Maggie; Gonzalez, Rachel I; Park, Angela M; Ross, David B; Morgan, Tim R; Backus, Lisa I

2018-06-01

The Department of Veterans Affairs (VA) has made significant progress in treating hepatitis C virus, experiencing more than a 75% reduction in veterans remaining to be treated since the availability of oral direct-acting antivirals. Hepatitis C Innovation Teams use lean process improvement and system redesign, resulting in practice models that address gaps in care. The key to success is creative improvements in veteran access to providers, including expanded use of nonphysician providers, video telehealth, and electronic technologies. Population health management tools monitor and identify trends in care, helping the VA tailor care and address barriers. Published by Elsevier Inc.

Bush Sophora Root polysaccharide and its sulfate can scavenge free radicals resulted from duck virus hepatitis.

PubMed

Chen, Yun; Xiong, Wen; Zeng, Ling; Wang, Yu; Zhang, Shuaibing; Xu, Meiyun; Song, Meiyun; Wang, Yixuan; Du, Hongxu; Liu, Jiaguo; Wang, Deyun; Wu, Yi; Hu, Yuanliang

2014-05-01

In order to study the antioxidant effect of Bush Sophora Root polysaccharide (BSRPS) and its sulfate on anti-duck virus hepatitis (DVH), sulfated Bush Sophora Root polysaccharide (sBSRPS) was prepared by chlorosulfonic acid-pyridine method. Ducklings were fed with BSRPS and sBSRPS after challenged DHAV. Death was monitored, evaluation indexes of peroxidative and hepatic injury at the initial (4th and 8th hour) and later (54th hour) stages were detected. The results showed a fine treatment effect of BSRPS and sBSRPS. Visual hepatic pathological injury severities were less serious after the treatment. At the initial stage, free radical levels in all groups were the same, and BSRPS and sBSRPS reduced the hepatic injury through inhibiting virus replication. At the later stage, mass free radicals were detected in VC group while free radical levels in BSRPS and sBSRPS groups were significantly lower than VC group. The antioxidant effect of BSRPS and sBSRPS might alleviate the hepatic injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Examining Hepatitis, A and B Vaccination, and HBV Reactivation Monitoring During Direct-Acting Antiviral Therapy for Hepatitis C.

PubMed

Davison, John; O'Shea, Amy; Waterbury, Nancee; Villalvazo, Yolanda

2018-05-30

The objective of this study was to examine Hepatitis A (HAV) and Hepatitis B (HBV) screening, and the risk of HBV reactivation during Hepatitis C (HCV) therapy with direct-acting antivirals (DAAs). A retrospective chart review was performed of patients treated with second generation DAA therapy from January 2014 to September 2016 at the Iowa City VA Healthcare System. In total 409 patients initiated HCV treatment, 308 (75%) and 241 (59%) were HAV and HBV vaccine eligible, respectively. Among those, 24 (8%) received a HAV vaccine, while only 20 (8%) received a HBV vaccine. Of these, 7 patients initiating an immunization in the clinic had record of completing the series. Further, 101 patients had a reactive Hepatitis B core Antibody indicating previous HBV infection, and 3 of these were tested for HBV reactivation during HCV therapy. Overall, the assessment found low rates of HAV and HBV vaccine administration, indicating missed opportunities for preventative care during HCV therapy. With the known risk of HBV reactivation with DAAs, the need for HAV and HBV screening is essential.

Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System.

PubMed

Bersoff-Matcha, Susan J; Cao, Kelly; Jason, Mihaela; Ajao, Adebola; Jones, S Christopher; Meyer, Tamra; Brinker, Allen

2017-06-06

Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. To assess whether HBV-R is a safety concern in patients receiving HCV DAAs. Descriptive case series. U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). 29 patients with HBV-R receiving HCV DAAs. Clinical and laboratory data. The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others. The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported. Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV-HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection. None.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

A population-based prevalence study of hepatitis A, B and C virus using oral fluid in Flanders, Belgium.

PubMed

Quoilin, Sophie; Hutse, Veronik; Vandenberghe, Hans; Claeys, Françoise; Verhaegen, Els; De Cock, Liesbet; Van Loock, Frank; Top, Geert; Van Damme, Pierre; Vranckx, Robert; Van Oyen, Herman

2007-01-01

Ten years after the first seroprevalence study performed in Flanders, the aim of this cross sectional study was to follow the evolution of hepatitis A, B and C prevalence. The prevalence of hepatitis A antibodies, hepatitis B surface antigen and hepatitis C antibodies was measured in oral fluid samples collected by postal survey. Using the National Population Register, an incremental sampling plan was developed to obtain a representative sampling of the general population. A total of 24,000 persons were selected and 6,000 persons among them contacted in a first wave. With 1834 participants a response rate of 30.6% was achieved. The prevalence was weighted for age and was 20.2% (95% CI 19.43-21.08) for hepatitis A, 0.66% (95% CI 0.51-0.84) for hepatitis B surface antigen and 0.12% (95% CI 0.09-0.39) for hepatitis C. The prevalence of hepatitis A and C in the Flemish population is lower in 2003 compared with the results of the study performed in 1993. The difference may be due to a real decrease of the diseases but also to differences in the methodology. The prevalence of hepatitis B surface antigen remains stable. Considering the 30% response rate and the high quality of the self-collected samples as reflect of a good participation of the general population, saliva test for prevalence study is a good epidemiological monitoring tool.

Community-based prevention of hepatitis-B-related liver cancer: Australian insights

PubMed Central

Kansil, Melanie Q; Porwal, Mamta; Penman, Andrew G; George, Jacob

2014-01-01

Abstract Problem Although most primary hepatocellular cancers (HCCs) are attributable to chronic viral hepatitis and largely preventable, such cancers remain a leading cause of cancer-related mortality wherever chronic hepatitis B is endemic. Approach Many HCCs could be prevented by increasing awareness and knowledge of hepatitis B, optimizing the monitoring of chronic hepatitis B and using antiviral treatments – but there are gaps in the implementation of such strategies. Local setting The “B Positive” programme, based in Sydney, Australia, is designed to improve hepatitis-B-related health outcomes among immigrants from countries with endemic hepatitis B. The programme offers information about disease screening, vaccination and treatment options, as well as optimized access to care. Relevant changes The B Positive programme has been informed by economic modelling. The programme offers culturally tailored education on chronic hepatitis B to target communities and their health practitioners and regular follow-up through a population-based registry of cases. Lessons learnt As the costs of screening for chronic hepatitis B and follow-up are relatively low and less than one in every four cases may require antiviral drugs, optimizing access to treatment seems an appropriate and cost-effective management option. The identification and accurate staging of cases and the judicious use of antiviral medications are predicated upon an informed and educated health workforce. As establishing community trust is a lengthy process, delaying the implementation of programmes against chronic hepatitis B until antiviral drugs become cheaper is unwarranted. PMID:24839327

Application of thoron interference as a tool for simultaneous measurement of radon and thoron with a pulse ionisation chamber.

PubMed

Tripathi, R M; Sumesh, C G; Vinod Kumar, A; Puranik, V D

2013-07-01

Pulse ionisation chamber (PIC)-based monitors measuring radioactive gas radon ((222)Rn) without energy discrimination will have interference due to thoron ((220)Rn) present in the atmosphere. A technique has been developed to use this property of interference for simultaneous measurement of radon and thoron gas. These monitors work on the principle of counting of gross alphas emitted from radon and its progeny. A theoretical model has been developed for the variation of thoron sensitivity with respect to the flow rate of gas through the monitor. The thoron sensitivity of the monitor is found to vary with the flow rate of gas through the monitor. Using this sensitivity, the sampling procedure has been developed and verified for simultaneous measurement of radon and thoron. The PIC-measured radon and thoron concentration using this procedure agrees well with those measured by using standard radon and thoron discriminating monitor.

Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease

PubMed Central

Boaru, Sorina Georgiana; Merle, Uta; Uerlings, Ricarda; Zimmermann, Astrid; Flechtenmacher, Christa; Willheim, Claudia; Eder, Elisabeth; Ferenci, Peter; Stremmel, Wolfgang; Weiskirchen, Ralf

2015-01-01

Wilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the copper-transporting ATPase gene (Atp7b) is disrupted revealed a drastic, time-dependent accumulation of hepatic copper that is accompanied by formation of regenerative nodes resembling cirrhosis. Therefore, these mice represent an excellent exploratory model for Wilson's disease. However, the precise time course in hepatic copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic metal content in wild-type and Atp7b deficient mice during ageing. We demonstrate that the age-dependent accumulation of hepatic copper is strictly associated with a simultaneous increase in iron and zinc, while the intrahepatic concentration and distribution of other metals or metalloids is not affected. The same findings were obtained in well-defined human liver samples that were obtained from patients suffering from Wilson's disease. We conclude that in Wilson's disease the imbalances of hepatic copper during ageing are closely correlated with alterations in intrahepatic iron and zinc content. PMID:25704483

18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

PubMed

Eshghi, Naghmehossadat; Lundeen, Tamara F; MacKinnon, Lea; Avery, Ryan; Kuo, Phillip H

2018-05-01

An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

Acute Liver Failure During Deferasirox Chelation: A Toxicity Worth Considering.

PubMed

Menaker, Nathan; Halligan, Katharine; Shur, Natasha; Paige, John; Hickling, Matthew; Nepo, Anne; Weintraub, Lauren

2017-04-01

This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox.

A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver

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

Shikanai, Mima; Asahina, Kinji; Iseki, Sachiko

2009-04-03

Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or {alpha}-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells becamemore » mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.« less

Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma.

PubMed

Tan, Ker-Kan; Bang, Shieh-Ling; Vijayan, Appasamy; Chiu, Ming-Terk

2009-09-01

Delayed diagnosis of patients with severe liver injuries is associated with an adverse outcome. As computed tomographic (CT) scan is not always available in the management of blunt abdominal trauma worldwide, the present study was undertaken to determine the accuracy of selected haematological markers in predicting the presence of hepatic injury and its severity after blunt abdominal trauma. A retrospective review of all patients with blunt abdominal trauma presented to our institution over a 3-year period was performed. Patients were excluded if they suffered penetrating injuries, died in the emergency department or if the required blood tests were not performed within 24h of the accident. The grading of the hepatic injury was verified using CT scans or surgical findings. Ninety-nine patients with blunt abdominal trauma had the required blood tests performed and were included in the study. The median injury severity score was 24 (range 4-75). Fifty-five patients had hepatic injuries, of which 47.3% were minor (Grades I and II) while 52.7% had major hepatic injuries (Grades III-V). There were no patients with Grade VI injuries. A raised ALT was strongly associated with presence of hepatic injuries (OR, 109.8; 95% CI, 25.81-466.9). This relation was also seen in patients with raised AST>2 times (OR, 21.33; 95% CI, 7.27-62.65). This difference was not seen in both bilirubin and ALP. ALT>2 times normal was associated with major hepatic injuries (OR, 7.15; 95% CI, 1.38-37.14; p=0.012) while patients with simultaneous raised AST>2 times and ALT>2 times had a stronger association for major hepatic injuries (OR, 8.44; 95% CI, 1.64-43.47). Abnormal transaminases levels are associated with hepatic injuries after blunt abdominal trauma. Patients with ALT and AST>2 times normal should be assumed to possess major hepatic trauma and managed accordingly. Patients with normal ALT, AST and LDH are unlikely to have major liver injuries.

Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout.

PubMed

Ehlken, H; Krishna-Subramanian, S; Ochoa-Callejero, L; Kondylis, V; Nadi, N E; Straub, B K; Schirmacher, P; Walczak, H; Kollias, G; Pasparakis, M

2014-11-01

Hepatocellular carcinoma (HCC) usually develops in the context of chronic hepatitis triggered by viruses or toxic substances causing hepatocyte death, inflammation and compensatory proliferation of liver cells. Death receptors of the TNFR superfamily regulate cell death and inflammation and are implicated in liver disease and cancer. Liver parenchymal cell-specific ablation of NEMO/IKKγ, a subunit of the IκB kinase (IKK) complex that is essential for the activation of canonical NF-κB signalling, sensitized hepatocytes to apoptosis and caused the spontaneous development of chronic hepatitis and HCC in mice. Here we show that hepatitis and HCC development in NEMO(LPC-KO) mice is triggered by death receptor-independent FADD-mediated hepatocyte apoptosis. TNF deficiency in all cells or conditional LPC-specific ablation of TNFR1, Fas or TRAIL-R did not prevent hepatocyte apoptosis, hepatitis and HCC development in NEMO(LPC-KO) mice. To address potential functional redundancies between death receptors we generated and analysed NEMO(LPC-KO) mice with combined LPC-specific deficiency of TNFR1, Fas and TRAIL-R and found that also simultaneous lack of all three death receptors did not prevent hepatocyte apoptosis, chronic hepatitis and HCC development. However, LPC-specific combined deficiency in TNFR1, Fas and TRAIL-R protected the NEMO-deficient liver from LPS-induced liver failure, showing that different mechanisms trigger spontaneous and LPS-induced hepatocyte apoptosis in NEMO(LPC-KO) mice. In addition, NK cell depletion did not prevent liver damage and hepatitis. Moreover, NEMO(LPC-KO) mice crossed into a RAG-1-deficient genetic background-developed hepatitis and HCC. Collectively, these results show that the spontaneous development of hepatocyte apoptosis, chronic hepatitis and HCC in NEMO(LPC-KO) mice occurs independently of death receptor signalling, NK cells and B and T lymphocytes, arguing against an immunological trigger as the critical stimulus driving hepatocarcinogenesis in this model.

Advanced Method for Isolation of Mouse Hepatocytes, Liver Sinusoidal Endothelial Cells, and Kupffer Cells.

PubMed

Liu, Jia; Huang, Xuan; Werner, Melanie; Broering, Ruth; Yang, Dongliang; Lu, Mengji

2017-01-01

Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen. A liberase-based perfusion technique in combination with a low-speed centrifugation and magnetic-activated cell sorting (MACS) led to the isolation and purification of HCs, KCs, and LSECs with high yields and purity.

Pegylated interferon-alpha2b plus ribavirin therapy in patients with hepatitis C and psychiatric disorders: results of a cohort study.

PubMed

Lang, Jean-Philippe; Melin, Pascal; Ouzan, Denis; Rotily, Michel; Fontanges, Thierry; Marcellin, Patrick; Chousterman, Michel; Cacoub, Patrice

2010-01-01

Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.

Method And System For Examining Biological Materials Using Low Power Cw Excitation Raman Spectroscopy.

DOEpatents

Alfano, Robert R.; Wang, Wubao

2003-05-06

A method and system for examining biological materials using low-power cw excitation Raman spectroscopy. A low-power continuous wave (cw) pump laser beam and a low-power cw Stokes (or anti-Stokes) probe laser beam simultaneously illuminate a biological material and traverse the biological material in collinearity. The pump beam, whose frequency is varied, is used to induce Raman emission from the biological material. The intensity of the probe beam, whose frequency is kept constant, is monitored as it leaves the biological material. When the difference between the pump and probe excitation frequencies is equal to a Raman vibrational mode frequency of the biological material, the weak probe signal becomes amplified by one or more orders of magnitude (typically up to about 10.sup.4 -10.sup.6) due to the Raman emission from the pump beam. In this manner, by monitoring the intensity of the probe beam emitted from the biological material as the pump beam is varied in frequency, one can obtain an excitation Raman spectrum for the biological material tested. The present invention may be applied to in the in vivo and/or in vitro diagnosis of diabetes, heart disease, hepatitis, cancers and other diseases by measuring the characteristic excitation Raman lines of blood glucose, cholesterol, serum glutamic oxalacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT), tissues and other corresponding Raman-active body constituents, respectively.

Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

PubMed Central

Martini, Andrea; Gallotta, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2015-01-01

Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. PMID:26689503

Simultaneous chromatic dispersion, polarization-mode-dispersion and OSNR monitoring at 40Gbit/s.

PubMed

Baker-Meflah, Lamia; Thomsen, Benn; Mitchell, John; Bayvel, Polina

2008-09-29

A novel method for independent and simultaneous monitoring of chromatic dispersion (CD), first-order PMD and OSNR in 40Gbit/s systems is proposed and demonstrated. This is performed using in-band tone monitoring of 5GHz, optically down-converted to a low intermediate-frequency (IF) of 10kHz. The measurement provides a large monitoring range with good accuracies for CD (4742+/-100ps/nm), differential group delay (DGD) (200+/-4ps) and OSNR (23+/-1dB), independently of the bit-rate. In addition, the use of electro-absorption modulators (EAM) for the simultaneous down-conversion of all channels and the use of low-speed detectors makes it cost effective for multi-channel operation.

Security warning system monitors up to fifteen remote areas simultaneously

NASA Technical Reports Server (NTRS)

Fusco, R. C.

1966-01-01

Security warning system consisting of 15 television cameras is capable of monitoring several remote or unoccupied areas simultaneously. The system uses a commutator and decommutator, allowing time-multiplexed video transmission. This security system could be used in industrial and retail establishments.

Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging

PubMed Central

Georgiou, Leonidas; Penny, Jeffrey; Nicholls, Glynis; Woodhouse, Neil; Blé, François-Xavier; Hubbard Cristinacce, Penny L.; Naish, Josephine H.

2017-01-01

Objective The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. Materials and Methods Ten healthy volunteers (age range, 18–29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. Results Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. Conclusions This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions. PMID:28002117

Hepatitis A in Poland in 2012.

PubMed

Baumann-Popczyk, Anna

2014-01-01

The aim of the article is evaluation of the epidemiological situation of hepatitis A in Poland in 2012. Assessment of epidemiological situation of hepatitis A was based on results from analysis of the annual bulletins: "Infectious diseases and poisonings in Poland in 2012", "Vaccinations in Poland in 2012", reports from individual cases and epidemiological investigations of outbreaks linked to hepatitis A, sent by Epidemiological Departments in Sanitary Epidemiological Stations to the Department of Epidemiology at NIPH-NIH. In Poland, 71 cases of hepatitis A were registered in 2012. The incidence of 0.17/ per 100 000 inhabitants was slightly higher than previous year. The incidence of hepatitis A ranged from 0.08/100 000 in Łódzkie and Podlaskie to 0.35/100 000 in Śląskie. The incidence of hepatitis A in men and women was at an approximate level and amounted to 0.19 and 0.18/100 000 respectively. The peak of incidence was recorded during the summer and autumn-winter months. In 2012 imported cases constituted 52.1% of all cases of hepatitis A. There were five outbreaks involving of 11 registered cases in 2012. In 2012, there was a slight increase in the incidence of hepatitis A in compared with the previous year. However, apart from that there were no significant changes in the epidemiological situation of hepatitis A. In Poland there is still very low endemicity for hepatitis A. Decreased incidence and the small number of people vaccinated against hepatitis A facilitates the accumulation of a fairly numerous population of persons susceptible to infection which is connected with the possibility to increase the number of cases of hepatitis A. Despite the fact that the current epidemiological situation of hepatitis A in Poland is good, the disease still requires monitoring and analysis within the framework of epidemiological surveillance system.

Eupatilin, isolated from Artemisia princeps Pampanini, enhances hepatic glucose metabolism and pancreatic beta-cell function in type 2 diabetic mice.

PubMed

Kang, Young-Jin; Jung, Un Ju; Lee, Mi-Kyung; Kim, Hye-Jin; Jeon, Seon-Min; Park, Yong Bok; Chung, Hae-Gon; Baek, Nam-In; Lee, Kyung Tae; Jeong, Tae-Sook; Choi, Myung-Sook

2008-10-01

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) was isolated from Artemisia princeps to investigate the dose-response effects on blood glucose regulation and pancreatic beta-cell function in type 2 diabetic mice. Db/db mice were divided into control (eupatilin-free, AIN-76 standard diet), low-Eupa (0.005g/100g diet) and high-Eupa (0.02g/100g diet) groups. The supplementation of eupatilin for 6 weeks significantly lowered fasting blood glucose concentration while it increased hepatic glycogen content. In particular, high-Eupa reduced hemoglobin A(1c) and plasma glucagon levels along with a simultaneous increase in plasma insulin and adiponectin levels. The supplementation of eupatilin significantly lowered hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, while it increased glucokinase activity in the liver. The pancreatic insulin concentration was higher in the eupatilin-supplemented groups. Also the pancreatic insulin concentration of eupatilin groups was higher than the control group. These results suggest that eupatilin played the role of an antidiabetic functional component in A. princeps by enhancing hepatic and plasma glucose metabolism as well as by increasing insulin secretion in type 2 diabetic mice.

Photoplethysmography beyond perfusion and oxygenation monitoring: Pulse wave analysis for hepatic graft monitoring

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

Akl, Tony; Wilson, Mark A.; Ericson, Milton Nance

2014-01-01

Photoplethysmography is a widely used technique in monitoring perfusion and blood oxygen saturation by using the amplitude of the pulsatile signal on one or multiple wavelengths. However, the pulsatile signal carries in its waveform a substantial amount of information about the mechanical properties of the tissue and vasculature under investigation that is still yet to be utilized to its full potential. In this work, we present the feasibility of pulse wave analysis for the application of monitoring hepatic implants and diagnosing graft complications. In particular, we show the possibility of computing the slope of the pulse during the diastole phasemore » to assess the location of vascular complications when they take place. This hypothesis was tested in a series of in vitro experiments using a PDMS based phantom mimicking the optical and mechanical properties of the portal vein. The emptying time of the vessel increased from 305 ms to 515 ms when an occlusion was induced downstream from the phantom. However, in the case of upstream occlusions, the emptying time remained constant. In both cases, a decrease in the amplitude of the pulse was recorded indicating the drop in flow levels. In addition, we show that quantifying the emptying time of the vasculature under investigation can be used to assess its compliance. The emptying time decreased from 305 ms for phantoms with compliance of 15 KPa to 195 ms for phantoms with compliance of 100 KPa. These compliance levels mimic those seen for normal and fibrotic hepatic tissue respectively.« less

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

PubMed Central

Cheong, Hae-Kwan; Kim, Eun A; Choi, Jung-Keun; Choi, Sung-Bong; Suh, Jeong-Ill; Choi, Dae Seob; Kim, Jung Ran

2007-01-01

Context Industrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers. Case presentation Five workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis. Discussion Infectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction–type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them. Relevance to clinical or professional practice In the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers’ health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent. PMID:17366828

Grand rounds: an outbreak of toxic hepatitis among industrial waste disposal workers.

PubMed

Cheong, Hae-Kwan; Kim, Eun A; Choi, Jung-Keun; Choi, Sung-Bong; Suh, Jeong-Ill; Choi, Dae Seob; Kim, Jung Ran

2007-01-01

Industrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers. Five workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis. Infectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction-type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them. In the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers' health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent.

Sequential surgical resection of hepatic and pulmonary metastases from colorectal cancer

PubMed Central

Oevermann, Elisabeth; Killaitis, Claudia; Kujath, Peter; Hoffmann, Martin; Bruch, Hans-Peter

2010-01-01

Background Resection of isolated hepatic or pulmonary metastases from colorectal cancer is widely accepted and associated with a 5-year survival rate of 25–40%. The value of aggressive surgical management in patients with both hepatic and pulmonary metastases still remains a controversial area. Materials and methods A retrospective review of 1,497 patients with colorectal carcinoma (CRC) was analysed. Of 73 patients identified with resection of CRC and, at some point in time, both liver and lung metastases, 17 patients underwent metastasectomy (resection group). The remaining 56 patients comprised the non-resection group. Primary tumour, hepatic and pulmonary metastases of all patients were surgically treated in our department of surgery, and the results are that of a single institution. Results The resection group had a 3-year survival of 77%, a 5-year survival of 55% and a 10-year survival of 18%; median survival was 98 months. The longest overall survival was 136 months; six patients are still alive. In the resection group, overall survival was significantly higher than in the non-resection group (p < 0.01). Independent from the chronology of metastasectomy, 5-year survival was 55% with respect to the primary resection, 28% with respect to the first metastasectomy and 14% with respect to the second metastasectomy. A disease-free interval (>18 months), stage III (UICC) and age (<70 years) were found to be significant prognostic factors for overall survival. Conclusion Our report strongly supports aggressive surgical therapy in patients with both hepatic and pulmonary metastases from CRC. Overall survival for surgically treated selected patients with both hepatic and pulmonary metastases from CRC is comparable to hepatic or pulmonary metastasectomy. Simultaneous metastases tend to have a poorer outcome than metachronous metastases. PMID:20165954

[EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

PubMed

Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

2017-02-01

Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

PubMed Central

Houin, Satya S.; Rozance, Paul J.; Brown, Laura D.; Hay, William W.; Wilkening, Randall B.

2014-01-01

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 (P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 (P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia (P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia. PMID:25516551

Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model.

PubMed

Zhang, Chi; Lu, Xuemian; Tan, Yi; Li, Bing; Miao, Xiao; Jin, Litai; Shi, Xue; Zhang, Xiang; Miao, Lining; Li, Xiaokun; Cai, Lu

2012-01-01

Zinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated. Type 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N',N'-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes. Hepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3β phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5-1.0 µM could be completely prevented by simultaneous Zn supplementation at the dose range of 30-50 µM. Zn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.

Hepatitis A vaccination during an outbreak among gay men in Montréal, Canada, 1995-1997

PubMed Central

Allard, R; Beauchemin, J; Bedard, L; Dion, R; Tremblay, M; Carsley, J

2001-01-01

STUDY OBJECTIVE—To evaluate an intervention designed to curtail an outbreak of hepatitis A among gay men, especially the young and sexually active, by promoting their free vaccination.
DESIGN—The study analysed routine passive surveillance data, carried out questionnaire and serological surveys of vaccinees, and surveys among the target population in non-clinical venues.
SETTING AND INTERVENTION—15 000 free doses of hepatitis A vaccine were made available through clinics with large gay clienteles, or at gay events, and advertised by various means, in Montréal, Canada, from August 1996 to November 1997. Simultaneous vaccination against hepatitis B (always free for gay men) was also encouraged.
PARTICIPANTS—Information was obtained from persons with the disease during the epidemic period, a sample of men requesting vaccination, and five community samples of gay men.
MAIN RESULTS—The outbreak involved 376 gay men and the vaccine was distributed to approximately 10 000. Vaccinees were older than cases, but had many sex partners and comprised more food handlers. Special vaccination clinics at gay events were well attended but did not reach more high risk men than regular medical venues. A self reported vaccine coverage of 49% was achieved, but 26% of vaccinees already had anti-HAV antibodies. Disease incidence declined rapidly during the campaign.
CONCLUSIONS—The intervention nearly tripled self reported hepatitis A vaccine coverage but its late start precludes proving that it caused the subsequent drop in incidence. However, it also increased hepatitis B vaccination and it is believed it improved links between gay men, public health, clinicians and community groups.


Keywords: hepatitis A; immunisation; homosexuality PMID:11238580

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Jeon, Seon-Min; Lee, Ki-Teak; Choi, Myung-Sook

2011-01-20

Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

[Hepatic failure due to nevirapine treatment for HIV infection].

PubMed

Mens, Helene; Katzenstein, Terese L

2005-11-14

Two cases of hepatic failure due to nevirapine treatment are reported. One patient erroneously took double dosing of nevirapine, while the other patient did not attend the scheduled laboratory control two weeks after the initiation of nevirapine treatment. In spite of maximal conservative treatment, this patient died five days after admission. These cases emphasise the importance of giving patients thorough instructions as well as doing clinical and laboratory monitoring of patients receiving highly active antiretroviral treatment (HAART).

Imaging-based quantification of hepatic fat: methods and clinical applications.

PubMed

Ma, Xiaozhou; Holalkere, Nagaraj-Setty; Kambadakone R, Avinash; Mino-Kenudson, Mari; Hahn, Peter F; Sahani, Dushyant V

2009-01-01

Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis, steatohepatitis with inflammatory changes, and end-stage liver disease with fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and obesity and may be secondary to alcohol and drug use, toxins, viral infections, and metabolic diseases. Detection and quantification of liver fat have many clinical applications, and early recognition is crucial to institute appropriate management and prevent progression. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but results are vulnerable to sampling error. Moreover, it can cause morbidity and complications and cannot be repeated often enough to monitor treatment response. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. Ultrasonography is effective for detecting moderate or severe fatty infiltration but is limited by lack of interobserver reliability and intraobserver reproducibility. Computed tomography allows quantitative and qualitative evaluation and is generally highly accurate and reliable; however, the results may be confounded by hepatic parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance (MR) imaging with appropriate sequences (eg, chemical shift techniques) has similarly high sensitivity, and MR spectroscopy provides unique advantages for some applications. However, both are expensive and too complex to be used to monitor steatosis. (c) RSNA, 2009.

Symptomatic Perihepatic Fluid Collections After Hepatic Resection in the Modern Era.

PubMed

Konstantinidis, Ioannis T; Mastrodomenico, Pedro; Sofocleous, Constantinos T; Brown, Karen T; Getrajdman, George I; Gönen, Mithat; Allen, Peter J; Kingham, T Peter; DeMatteo, Ronald P; Fong, Yuman; Jarnagin, William R; D'Angelica, Michael I

2016-04-01

Improvements in liver surgery have led to decreased mortality rates. Symptomatic perihepatic collections (SPHCs) requiring percutaneous drainage remain a significant source of morbidity. A single institution's prospectively maintained hepatic resection database was reviewed to identify patients who underwent hepatectomy between January 2004 and February 2012. Data from 2173 hepatectomies performed in 2040 patients were reviewed. Overall, 200 (9%) patients developed an SPHC, the majority non-bilious (75.5%) and infected (54%). Major hepatic resections, larger than median blood loss (≥360 ml), use of surgical drains, and simultaneous performance of a colorectal procedure were associated with an SPHC on multivariate analysis. Non-bilious, non-infected (NBNI) collections were associated with lower white blood cell (WBC) counts, absence of a bilio-enteric anastomosis, use of hepatic arterial infusion pump (HAIP), and presence of metastatic disease, and resolved more frequently with a single interventional radiology (IR) procedure (85 vs. 46.5%, p < 0.001) more quickly (15 vs. 30 days, p = 0.001). SPHCs developed in 9% of patients in a modern series of hepatic resections, and in one third were non-bilious and non-infected. In the era of modern interventional radiology, the need for re-operation for SPHC is exceedingly rare. A significant proportion of minimally symptomatic SPHC patients may not require drainage, and strategies to avoid unnecessary drainage are warranted.

[Features of the effect of bemethyl on glycogen metabolism in hepatocytes of pathological changed human liver].

PubMed

Kudriavtseva, M V; Bezborodkina, N N; Okovityĭ, S V; Ivanova, O V; Kudriavtsev, B N

2002-01-01

Effect of actoprotector bemithyl (2-ethylthiobenzimidazole hydrobromide) on glycogen metabolism in hepatocytes of patients with chronic hepatitis and liver cirrhosis was investigated. Using cytofluorimetric method, the content of glycogen and its fractions in isolated hepatocytes was measured. The treatment with bemithyl resulted in a decrease in glycogen levels in hepatocytes, and in a marked restoration of fractional glycogen composition as compared to the basic therapy. Besides, it was established that the degree of glycogen decrease in cells of patients with chronic hepatitis depended on the increase of glucose-6-phosphatase activity (r = 0.75, P < 0.05), and on the levels of glycogen in hepatocytes prior to bemitil treatment (r = = 0.87, P < 0.01). Positive changes in glycogen metabolism after bemithyl treatment are pronounced in patients with chronic hepatitis. These positive alterations take place simultaneously with the conservation of basic structural disturbances in the liver parenchyma. However, even in this case, the indices of glycogen metabolism do not reach the normal levels.

Prevalence of hepatitis A virus in bivalve molluscs sold in Granada (Spain) fish markets.

PubMed

Moreno Roldán, Elena; Espigares Rodríguez, Elena; Espigares García, Miguel; Fernández-Crehuet Navajas, Milagros

2013-06-01

Viruses are the leading cause of foodborne illness associated with the consumption of raw or slightly cooked contaminated shellfish. The aim of this study was to evaluate the prevalence of hepatitis A virus in molluscs. Standard and real-time reverse transcription-polymerase chain reaction procedures were used to monitor bivalve molluscs from the Granada fish markets (southern Spain) for this human enteric virus. Between February 2009 and October 2010, we collected a total of 329 samples of different types of bivalve molluscs (mussels, smooth clams, striped venus, and grooved clams). The results showed the presence of hepatitis A virus in 8.5% of the 329 samples analyzed. We can therefore confirm that conventional fecal indicators are unreliable for demonstrating the presence or absence of viruses. The presence of hepatitis A virus in molluscs destined for human consumption is a potential health risk in southern Spain.

Aeromonas caviae inhibits hepatic enzymes of the phosphotransfer network in experimentally infected silver catfish: Impairment on bioenergetics.

PubMed

Baldissera, M D; Souza, C F; Verdi, C M; Dos Santos, K L M; Da Veiga, M L; da Rocha, M I U M; Santos, R C V; Vizzotto, B S; Baldisserotto, B

2018-03-01

Several studies have been demonstrated that phosphotransfer network, through the adenylate kinase (AK) and pyruvate kinase (PK) activities, allows for new perspectives leading to understanding of disease conditions associated with disturbances in energy metabolism, metabolic monitoring and signalling. In this sense, the aim of this study was to evaluate whether experimental infection by Aeromonas caviae alters hepatic AK and PK activities of silver catfish Rhamdia quelen. Hepatic AK and PK activities decreased in infected animals compared to uninfected animals, as well as the hepatic adenosine triphosphate (ATP) levels. Also, a severe hepatic damage was observed in the infected animals due to the presence of dilation and congestion of vessels, degeneration of hepatocytes and loss of liver parenchyma architecture and sinusoidal structure. Therefore, we have demonstrated, for the first time, that experimental infection by A. caviae inhibits key enzymes linked to the communication between sites of ATP generation and ATP utilization. Moreover, the absence of a reciprocal compensatory mechanism between these enzymes contributes directly to hepatic damage and for a severe energetic imbalance, which may contribute to disease pathophysiology. © 2017 John Wiley & Sons Ltd.

Normalized methodology for medical infrared imaging

NASA Astrophysics Data System (ADS)

Vargas, J. V. C.; Brioschi, M. L.; Dias, F. G.; Parolin, M. B.; Mulinari-Brenner, F. A.; Ordonez, J. C.; Colman, D.

2009-01-01

A normalized procedure for medical infrared imaging is suggested, and illustrated by a leprosy and hepatitis C treatment follow-up, in order to investigate the effect of concurrent treatment which has not been reported before. A 50-year-old man with indeterminate leprosy and a 20-year history of hepatitis C was monitored for 587 days, starting from the day the patient received treatment for leprosy. Standard therapy for hepatitis C started 30 days later. Both visual observations and normalized infrared imaging were conducted periodically to assess the response to leprosy treatment. The primary end points were effectiveness of the method under different boundary conditions over the period, and rapid assessment of the response to leprosy treatment. The patient achieved sustained hepatitis C virological response 6 months after the end of the treatment. The normalized infrared results demonstrate the leprosy treatment success in spite of the concurrent hepatitis C treatment, since day 87, whereas repigmentation was visually assessed only after day 182, and corroborated with a skin biopsy on day 390. The method detected the effectiveness of the leprosy treatment in 87 days, whereas repigmentation started only in 182 days. Hepatitis C and leprosy treatment did not affect each other.

42 CFR 494.30 - Condition: Infection control.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (with the exception of screening for hepatitis C), found in “Recommendations for Preventing Transmission... devices, and equipment. (b) Standard: Oversight. The facility must— (1) Monitor and implement biohazard...

Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper.

PubMed

Sarmati, L; Andreoni, M; Antonelli, G; Arcese, W; Bruno, R; Coppola, N; Gaeta, G B; Galli, M; Girmenia, C; Mikulska, M; Pane, F; Perno, C F; Picardi, M; Puoti, M; Rambaldi, A; Svicher, V; Taliani, G; Gentile, G

2017-12-01

Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

PubMed

van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

2016-08-01

Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous quantitation of two direct acting hepatitis C antivirals (sofosbuvir and daclatasvir) by an HPLC-UV method designated for their pharmacokinetic study in rabbits.

PubMed

Atia, Noha N; El-Shaboury, Salwa R; El-Gizawy, Samia M; Abo-Zeid, Mohammad Nabil

2018-05-22

Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λ max ; 260 and 313 nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7 min on C 18 analytical column with acetonitrile-10 mM acetate buffer of pH 5.0 at a flow rate of 1.0 mL min -1 . The linear ranges were 1-20 μg mL -1 for SOF and 0.6-6 μg mL -1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19 μg mL -1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) for dynamic contrast-enhanced MRI of liver.

PubMed

Ning, Jia; Sun, Yongliang; Xie, Sheng; Zhang, Bida; Huang, Feng; Koken, Peter; Smink, Jouke; Yuan, Chun; Chen, Huijun

2018-05-01

To propose a simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) method for liver dynamic contrast-enhanced MRI. The proposed SAHA simultaneously acquired high temporal-resolution 2D images for vascular input function extraction using Cartesian sampling and 3D large-coverage high spatial-resolution liver dynamic contrast-enhanced images using golden angle stack-of-stars acquisition in an interleaved way. Simulations were conducted to investigate the accuracy of SAHA in pharmacokinetic analysis. A healthy volunteer and three patients with cirrhosis or hepatocellular carcinoma were included in the study to investigate the feasibility of SAHA in vivo. Simulation studies showed that SAHA can provide closer results to the true values and lower root mean square error of estimated pharmacokinetic parameters in all of the tested scenarios. The in vivo scans of subjects provided fair image quality of both 2D images for arterial input function and portal venous input function and 3D whole liver images. The in vivo fitting results showed that the perfusion parameters of healthy liver were significantly different from those of cirrhotic liver and HCC. The proposed SAHA can provide improved accuracy in pharmacokinetic modeling and is feasible in human liver dynamic contrast-enhanced MRI, suggesting that SAHA is a potential tool for liver dynamic contrast-enhanced MRI. Magn Reson Med 79:2629-2641, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil.

PubMed

Eichelbaum, M; Somogyi, A; von Unruh, G E; Dengler, H J

1981-01-01

Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.

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

PubMed

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

2015-05-26

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

Extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without malignancy: a case report.

PubMed

Yoon, Young-Min; Kang, Da-Yeong; Kim, Da-Young; Seo, Jun-Won; Lim, Hyun-Jong; Lee, Hee-Jeong; Park, Sang-Gon

2016-06-01

Alpha-fetoprotein is produced by a variety of tumors such as hepatocellular carcinoma, hepatoblastoma, and germ cell tumors of the ovary and testes. However, we present a case of significantly elevated serum alpha-fetoprotein without evidence of malignant disease in a patient who is a carrier of chronic hepatitis B. A 60-year-old Korean man presented with markedly increased alpha-fetoprotein (2350 ng/mL; normal <5 ng/mL). Various diagnostic evaluations, including computed tomography of the abdomen and thorax and ultrasonography of the abdomen and testes, showed liver cirrhosis and mild splenomegaly; however, no mass was detected in the liver, testes, or other organs scanned. The laboratory findings showed elevated liver function, positivity for hepatitis B e antigen, and a marked increase in hepatitis B virus deoxyribonucleic acid copy number (>7 × 105 IU/mL). Our patient was diagnosed with acute exacerbation of chronic hepatitis B, and we presumed that this condition might be related to extremely elevated alpha-fetoprotein. When our patient was treated with entecavir, the serum alpha-fetoprotein level immediately decreased, in parallel with the hepatitis B virus deoxyribonucleic acid copy number. We report a rare case of extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without any malignancy, and a decrease in this tumor marker simultaneous with a decrease in hepatitis B virus deoxyribonucleic acid copy number on entecavir treatment. This case report is important due to the rarity of the case; furthermore, it provides details of a diagnostic process for a variety of benign diseases and malignant tumors that should be considered in patients with elevated alpha-fetoprotein. Thus, we present a case report, along with a review, that will be helpful for diagnosis and treatment of patients with elevated alpha-fetoprotein.

Medium chain triglycerides and hepatic encephalopathy

PubMed Central

Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

1974-01-01

The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy. PMID:4841275

18-F-FDG PET-CT in Monitoring of Chemotherapeutic Effect in a Case of Metastatic Hepatic Epithelioid Hemangioendothelioma

PubMed Central

Shamim, Shamim Ahmed; Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Roy, Shambo Guha

2017-01-01

Hepatic epithelioid hemangioendothelioma is a rare variant of mesenchymal tumor. Surgical resection or partial hepatectomy is the treatment of choice in the case of localized disease. However, in metastatic cases, chemotherapeutic drugs targeting the tyrosine kinase are being used. We hereby present 18-F-fludeoxyglucose positron emission tomography-computed tomography findings in a case of a 35-year old woman with metastatic HEHE showing significant response to Sorafenib therapy after 6 months. PMID:28680215

18-F-FDG PET-CT in Monitoring of Chemotherapeutic Effect in a Case of Metastatic Hepatic Epithelioid Hemangioendothelioma.

PubMed

Shamim, Shamim Ahmed; Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Roy, Shambo Guha

2017-01-01

Hepatic epithelioid hemangioendothelioma is a rare variant of mesenchymal tumor. Surgical resection or partial hepatectomy is the treatment of choice in the case of localized disease. However, in metastatic cases, chemotherapeutic drugs targeting the tyrosine kinase are being used. We hereby present 18-F-fludeoxyglucose positron emission tomography-computed tomography findings in a case of a 35-year old woman with metastatic HEHE showing significant response to Sorafenib therapy after 6 months.

[Blood component donors and recipients as linked study objects in epidemiological population-based surveys].

PubMed

Garmaeva, T Ts; Kulikov, S M

2015-01-01

A population of hematological cancer patients as recipients of many blood components and that of donors of blood components and bone marrow are related to the common event of contamination with viruses of blood-borne infections; which occurs and is detectable during long-term treatment and follow-up. They share interaction traits and diverse communication mechanisms, which call for complex interrelated trials in both groups with a mandatory epidemiological evidenced-based investigation of all cases of posttransfusion hepatitis B and/or C. The identity of infection with hepatitis B and C viruses, human immunodeficiency virus, and their association should be simultaneously studied in the populations of both donors and recipients of blood components and bone marrow.

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

PubMed

Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Diagnostic tests for hepatitis C: Recent trends in electrochemical immunosensor and genosensor analysis

PubMed Central

Uliana, Carolina V; Riccardi, Carla S; Yamanaka, Hideko

2014-01-01

Hepatitis C is a liver disease that is transmitted through contact with the blood of an infected person. An estimated 150 million individuals worldwide have been chronically infected with the hepatitis C virus (HCV). Hepatitis C shows significant genetic variation in the global population, due to the high rate of viral RNA mutation. There are six variants of the virus (HCV genotypes 1, 2, 3, 4, 5, and 6), with 15 recorded subtypes that vary in prevalence across different regions of the world. A variety of devices are used to diagnose hepatitis C, including HCV antibody test, HCV viral load test, HCV genotype test and liver biopsy. Rapid, inexpensive, sensitive, and robust analytical devices are therefore essential for effective diagnosis and monitoring of disease treatment. This review provides an overview of current electrochemical immunosensor and genosensor technologies employed in HCV detection. There are a limited number of publications showing electrochemical biosensors being used for the detection of HCV. Due to their simplicity, specificity, and reliability, electrochemical biosensor devices have potential clinical applications in several viral infections. PMID:25400433

Hepatic Enzyme Alterations in HIV Patients on Antiretroviral Therapy: A Case-Control Study in a Hospital Setting in Ghana.

PubMed

Osakunor, Derick Nii Mensah; Obirikorang, Christian; Fianu, Vincent; Asare, Isaac; Dakorah, Mavis

2015-01-01

Diagnosing hepatic injury in HIV infection can be a herculean task for clinicians as several factors may be involved. In this study, we sought to determine the effects of antiretroviral therapy (ART) and disease progression on hepatic enzymes in HIV patients. A case-control study conducted from January to May 2014 at the Akwatia Government Hospital, Eastern region, Ghana, The study included 209 HIV patients on ART (designated HIV-ART) and 132 ART-naive HIV patients (designated HIV-Controls). Data gathered included demography, clinical history and results of blood tests for hepatic enzymes. We employed the Fisher's, Chi-square, unpaired t-test and Pearson's correlation in analysis, using GraphPad Prism and SPSS. A P value < 0.05 was considered significant. Median CD4 lymphocyte count of HIV-ART participants (604.00 cells/mm3) was higher than that of HIV-Controls (491.50 cells/mm3; P = 0.0005). Mean values of ALP, ALT, AST and GGT did not differ between the two groups compared (P > 0.05). There was a significant positive correlation between hepatic enzymes (ALP, ALT, AST and GGT) for both groups (p < 0.01 each). Duration of ART correlated positively with ALT (p < 0.05). The effect size of disease progression on hepatic enzymes for both groups was small. Antiretroviral therapy amongst this population has minimal effects on hepatic enzymes and does not suggest modifications in therapy. Hepatic injury may occur in HIV, even in the absence of ART and other traditional factors. Monitoring of hepatic enzymes is still important in HIV patients.

Acute hepatitis in three patients with systemic juvenile idiopathic arthritis taking interleukin-1 receptor antagonist.

PubMed

Canna, Scott; Frankovich, Jennifer; Higgins, Gloria; Narkewicz, Michael R; Nash, S Russell; Hollister, J Roger; Soep, Jennifer B; Dragone, Leonard L

2009-12-22

We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA). Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during treatment with IL1RA were reviewed for evidence of sJIA flare, infection, macrophage activation syndrome (MAS), malignancy, and drug reaction. In all patients, hepatitis persisted despite cessation of known hepatotoxic drugs and in absence of known infectious triggers, until discontinuation of IL1RA. Liver biopsies had mixed inflammatory infiltrates with associated hepatocellular injury suggestive of an exogenous trigger. At the time of hepatitis, laboratory data and liver biopsies were not characteristic of MAS. In two patients, transaminitis resolved within one week of discontinuing IL1RA, the third improved dramatically in one month. Although sJIA symptoms improved significantly on IL1RA, it appeared that IL1RA contributed to the development of acute hepatitis. Hepatitis possibly occurred as a result of an altered immune response to a typical childhood infection while on IL1RA. Alternatively, hepatitis could have represented an atypical presentation of MAS in patients with sJIA taking IL1RA. Further investigation is warranted to determine how anti-IL1 therapies alter immune responsiveness to exogenous triggers in patients with immune dysfunction such as sJIA. Our patients suggest that close monitoring for hepatic and other toxicities is indicated when treating with IL1RA.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

PubMed

Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

2017-10-01

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Implementation of Hepatitis Information Management System in Iran.

PubMed

Reza, Safdari; Jebraeil, Farzi; Akbar, Nasiri Ali; Marjan, Ghazisaeedi; Reza, Taghavi Mohammad; Mehdi, Afshari; Mahlagha, Sargolzaee; Farhad, Taji

2015-11-17

Nowadays, hepatitis is of the most important health priorities around the world, where information plays a very significant role in specialized diseases prevention planning, and policy- and decision-making processes. Thus, this study addressed challenges of hepatitis information management and investigated the outcomes of establishing a hepatitis information management system to overcome such challenges. To this end, this research intended to study the implementation of an Electronic hepatitis information management system. This is an applied-developmental study with following specifications and procedures: preparation of study proposal and design, justification of the design's stakeholders, approval of the design by the Postgraduate Education Council of Faculty, determination of pilot hepatitis control center, software development, deciding on control, prevention, and treatment centers, and finally development of a network-based system for collecting and managing hepatitis information. Results indicated that the inconsistency and lack of integrity of data, as well as the lack of communication between related units prevented timely information register of viral hepatic patients and services that are provided to them. This inhibited the possibility of considering a follow-up process. However, the implementation of this system and involvement of relevant units greatly solved these problems. Results show that the implementation of an electronic system for the management of hepatitis control, prevention, and treatment is a regional and national requirement; since, this system with its empowered infrastructure is capable in providing desired services to all laboratories, counseling and health centers, specialized clinics, and physicians connected to the hepatitis network. This enables them to follow up and monitor patients' conditions. That mentioned system paves the way for the analysis of gathered information, managers' and specialists' access in different regions to the data for making appropriate and accurate decisions.

Implementation of Hepatitis Information Management System in Iran

PubMed Central

Reza, Safdari; Jebraeil, Farzi; Akbar, Nasiri Ali; Marjan, Ghazisaeedi; Reza, Taghavi Mohammad; Mehdi, Afshari; Mahlagha, Sargolzaee; Farhad, Taji

2016-01-01

Introduction: Nowadays, hepatitis is of the most important health priorities around the world, where information plays a very significant role in specialized diseases prevention planning, and policy- and decision-making processes. Thus, this study addressed challenges of hepatitis information management and investigated the outcomes of establishing a hepatitis information management system to overcome such challenges. To this end, this research intended to study the implementation of an Electronic hepatitis information management system. Methodology: This is an applied-developmental study with following specifications and procedures: preparation of study proposal and design, justification of the design’s stakeholders, approval of the design by the Postgraduate Education Council of Faculty, determination of pilot hepatitis control center, software development, deciding on control, prevention, and treatment centers, and finally development of a network-based system for collecting and managing hepatitis information. Findings: Results indicated that the inconsistency and lack of integrity of data, as well as the lack of communication between related units prevented timely information register of viral hepatic patients and services that are provided to them. This inhibited the possibility of considering a follow-up process. However, the implementation of this system and involvement of relevant units greatly solved these problems. Conclusion: Results show that the implementation of an electronic system for the management of hepatitis control, prevention, and treatment is a regional and national requirement; since, this system with its empowered infrastructure is capable in providing desired services to all laboratories, counseling and health centers, specialized clinics, and physicians connected to the hepatitis network. This enables them to follow up and monitor patients’ conditions. That mentioned system paves the way for the analysis of gathered information, managers’ and specialists’ access in different regions to the data for making appropriate and accurate decisions. PMID:26755478

Hepatitis C Test

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... monitor treatment: HCV RNA tests: HCV RNA test, Quantitative (HCV viral load) detects and measures the number ...

Intelligent MONitoring System for antiviral pharmacotherapy in patients with chronic hepatitis C (SiMON-VC).

PubMed

Margusino-Framiñán, Luis; Cid-Silva, Purificación; Mena-de-Cea, Álvaro; Sanclaudio-Luhía, Ana Isabel; Castro-Castro, José Antonio; Vázquez-González, Guillermo; Martín-Herranz, Isabel

2017-01-01

Two out of six strategic axes of pharmaceutical care in our hospital are quality and safety of care, and the incorporation of information technologies. Based on this, an information system was developed in the outpatient setting for pharmaceutical care of patients with chronic hepatitis C, SiMON-VC, which would improve the quality and safety of their pharmacotherapy. The objective of this paper is to describe requirements, structure and features of Si- MON-VC. Requirements demanded were that the information system would enter automatically all critical data from electronic clinical records at each of the visits to the Outpatient Pharmacy Unit, allowing the generation of events and alerts, documenting the pharmaceutical care provided, and allowing the use of data for research purposes. In order to meet these requirements, 5 sections were structured for each patient in SiMON-VC: Main Record, Events, Notes, Monitoring Graphs and Tables, and Follow-up. Each section presents a number of tabs with those coded data needed to monitor patients in the outpatient unit. The system automatically generates alerts for assisted prescription validation, efficacy and safety of using antivirals for the treatment of this disease. It features a completely versatile Indicator Control Panel, where temporary monitoring standards and alerts can be set. It allows the generation of reports, and their export to the electronic clinical record. It also allows data to be exported to the usual operating systems, through Big Data and Business Intelligence. Summing up, we can state that SiMON-VC improves the quality of pharmaceutical care provided in the outpatient pharmacy unit to patients with chronic hepatitis C, increasing the safety of antiviral therapy. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Hepatitis A Is a Health Hazard for Iranian Pilgrims Who Go to Holly Karbala: A Preliminary Report

PubMed Central

Ghasemian, Roya; Babamahmoodi, Farhang; Ahangarkani, Fatemeh

2016-01-01

Background Iraq is a highly endemic area for the prevalence of hepatitis A and annually hosts a large number of Iranian pilgrims, most of whom are susceptible to infection with the hepatitis A virus (HAV). Objectives This study reports the health hazard of hepatitis A for Iranian pilgrims who go to holly Karbala from the Mazandaran province. Patients and Methods In this cross-sectional study, the data of all patients with acute hepatitis A admitted in the Razi teaching hospital from November 23, 2014 to January 24, 2015, with a history of recently returning from holly Karbala or being exposed to Karbala pilgrims, were registered. Results A total number of nine patients were registered. Seven patients were male and two were female. The mean age was 30.11 ± 10.09.Two patients were from the same family. All patients had typical symptoms of acute hepatitis A. None of the patients died nor did fulminant occur in any patients. In addition, all patients were treated with supportive treatment and subsequently recovered. Conclusions This number of pilgrim patients with acute hepatitis A from a single province compels us to conduct more evaluations and follow up monitoring on all persons travelling to Karbala and be sensitive to early diagnoses of the pilgrims. In the future, it is important to be mindful of administering the HAV vaccine and Ig. PMID:27630729

Assessment of timeliness, representativeness and quality of data reported to Italy's national integrated surveillance system for acute viral hepatitis (SEIEVA).

PubMed

Tosti, M E; Longhi, S; de Waure, C; Mele, A; Franco, E; Ricciardi, W; Filia, A

2015-05-01

Periodic assessment of surveillance systems is recommended to verify whether they are appropriately monitoring the public health problem under surveillance. The aim of this study was to evaluate timeliness, data quality and representativeness of data reported to the Italian Integrated Epidemiological System for Acute Viral Hepatitis (SEIEVA). Cross-sectional analysis of surveillance data. Quantitative indicators were used to evaluate representativeness of reported cases, data quality, and timeliness between surveillance steps, for reports of acute viral hepatitis cases with date of onset of symptoms from 2009 to 2012 (N = 4516). Representativeness was 75%. Over 95% of records reported information on age, sex, city of residence, risk factors for hepatitis A and vaccination status. Information on risk factors for hepatitis B and C were reported less consistently (83%), as was information on early outcome (60%). Wide delays were found between surveillance steps. The system collects high quality data on acute viral hepatitis cases in Italy. Timeliness was found to be the main limit and needs to be improved by optimizing web-based reporting procedures, increasing communication with participating centres, improving feedback and increasing dissemination of surveillance results. The study highlights the importance of reporting timeliness to detect outbreaks of acute viral hepatitis. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Highly Sensitive Multiplex Assay for Detection of Human Immunodeficiency Virus Type 1 and Hepatitis C Virus RNA

PubMed Central

Giachetti, C.; Linnen, J. M.; Kolk, D. P.; Dockter, J.; Gillotte-Taylor, K.; Park, M.; Ho-Sing-Loy, M.; McCormick, M. K.; Mimms, L. T.; McDonough, S. H.

2002-01-01

Various nucleic acid assays have been developed and implemented for diagnostics and therapeutic monitoring of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections. The high-throughput, semiautomated assays described here were developed to provide a method suitable for screening plasma specimens for the presence of HIV-1 and HCV RNAs. Three assays were developed: a multiplex HIV-1/HCV assay for simultaneous detection of HIV-1 and HCV, and discriminatory assays for specific detection of HIV-1 and HCV. The assay systems utilize three proprietary technologies: (i) target capture-based sample preparation, (ii) transcription-mediated amplification (TMA), and (iii) hybridization protection assay (HPA). An internal control is incorporated into each reaction to control for every step of the assay and identify random false-negative reactions. The assays demonstrated a sensitivity of at least 100 copies/ml for each target, and they detected with similar sensitivity all major variants of HCV and HIV-1, including HIV-1 group O strains. Assay sensitivity for one virus was not affected by the presence of the other. The specificity of these TMA-driven assays was ≥99.5% in both normal donor specimens and plasma containing potentially interfering substances or other blood-borne pathogens. Statistical receiver operating characteristic plots of 1 − specificity versus sensitivity data determined very wide analyte cutoff values for each assay at the point at which the assay specificity and sensitivity were both ≥99.5%. The sensitivity, specificity, and throughput capability predict that these assays will be valuable for large-volume plasma screening, either in a blood bank setting or in other diagnostic applications. PMID:12089255

[Hepatitis B and C virus infection and the hepatocellular carcinoma in the East Amazon, Brazil].

PubMed

Miranda, Esther Castello Branco Mello; Moia, Lizomar de Jesus Pereira; Amaral, Ivanete do Socorro Abraçado; Barbosa, Maria Silvia de Brito; Conde, Simone Regina Souza da Silva; de Araújo, Marialva Tereza Ferreira; da Cruz, Ermelinda do Rosário Moutinho; Demachki, Samia; Bensabath, Gilberta; Soares, Manoel do Carmo Pereira

2004-01-01

In order to contribute to a better understanding of the possible role of hepatits B and C in the etiopathogenis of HCC in the East Amazon, there were studied 36 patients in Belém/PA. Serological hepatitis markers were evaluated and polymerase chain reaction assays were used to detect HBV-DNA and HCV-RNA. Alcohol abuse was observed in 33.3% and cirrhosis in 83.3%. In 88.9% of the sample, one or more hepatitis B markers were positive. Also, 8.3% those patients had anti-HCV simultaneously positive. The HBsAg serological test was positive in 58.3%; anti-HBc in 86%; anti-HBe in 85.7%; anti-HBe in 9.5%; IgM anti-HBc in 57.1%. The HBV DNA was found in 37.7% and in 65% of the HBsAg positive. The HCV RNA was detected in 8.5% and in 100% of the patients positive to anti-HCV. The AFP was above the normal value in 88.9% of patients, with levels up to 400ng/ml in 75% of them. In conclusion, hepatitis B virus infection seems to be important in the etiology of HCC and improving measures such immunization and screening in the risk population should be emphasyzed.

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

PubMed

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.

[Hepatic artery of the rat in experimental cirrhosis of the liver].

PubMed

Baĭbekov, I M; Vorozheĭkin, V M; Khoroshaev, V A; Khamidov, P M

1984-04-01

In 30 male rats of Wistar strain (20 more rats served as controls) thickness of the internal elastic membrane, that of the media, cross section area of the media and that of the lumen were define 3, 4, 5 and 6 months after the experiment was started. The initial changes in the hepatic artery structure are noted on the 4th month, however, differences in the parameters are not yet statistically significant. On the 5th month certain signs of hypertrophy in the smooth muscle cells of the media are clearly seen, as well as an increasing thickness of the internal elastic membrane and that of the tunica media. Simultaneously, the index of labelling the myocyte nuclei reaches its maximum. The increasing thickness of the arterial wall causes certain decrease in the lumen cross section area. The changes of all the parameters are statistically significant. In 6 months after the beginning of the experiment, a pronounced hyperelastosis develops in the wall of the hepatic artery; a part of the smooth muscle cells in the tunica media undergoes atrophy. The area of the vascular lumen decreases by 16%, comparing to the age control. The experimental data confirm certain clinical observations and reveal some features in the mechanism of pathological changes occurring in the hepatic artery wall at cirrhosis.

Simultaneous monitoring of independent gene expression patterns in two types of cocultured fibroblasts with different color-emitting luciferases

PubMed Central

Noguchi, Takako; Ikeda, Masaaki; Ohmiya, Yoshihiro; Nakajima, Yoshihiro

2008-01-01

Background Luciferase assay systems enable the real-time monitoring of gene expression in living cells. We have developed a dual-color luciferase assay system in which the expression of multiple genes can be tracked simultaneously using green- and red-emitting beetle luciferases. We have applied the system to monitoring independent gene expressions in two types of cocultured fibroblasts in real time. Results Two Rat-1 cell lines were established that stably express either green- or red-emitting luciferases under the control of the mBmal1 promoter, a canonical clock gene. We cocultured these cell lines, and gene expression profiles in both were monitored simultaneously. The circadian rhythms of these cell lines are independent, oscillating following their intrinsic circadian phases, even when cocultured. Furthermore, the independent rhythms were synchronized by medium change as an external stimulus. Conclusion Using this system, we successfully monitored independent gene expression patterns in two lines of cocultured fibroblasts. PMID:18416852

Mineral metabolism in dimethylnitrosamine-induced hepatic fibrosis.

PubMed

George, Joseph

2006-10-01

Complications such as ascites during the pathogenesis of hepatic fibrosis and cirrhosis may lead to several abnormalities in mineral metabolism. In the present investigation, we have monitored serum and liver concentrations of calcium, magnesium, sodium and potassium during experimentally induced hepatic fibrosis in rats. The liver injury was induced by intraperitoneal injections of dimethylnitrosamine (DMN; N-nitrosodimethylamine, NDMA) in doses 1 mg/100 g body weight on 3 consecutive days of each week over a period of 21 days. Calcium, magnesium, sodium and potassium were measured by atomic absorption spectrophotometry in the serum and liver on days 7, 14 and 21 after the start of DMN administration. Negative correlations were observed between liver function tests and serum mineral levels, except with albumin. Calcium, magnesium, potassium and sodium concentrations in the serum were decreased after the induction of liver injury. The liver calcium content was increased after DMN treatment. No change occurred in liver sodium content. However, magnesium and potassium content was significantly reduced in the hepatic tissue. The results suggest that DMN-induced hepatic fibrosis plays certain role in the alteration of essential elements. The low levels of albumin and the related ascites may be one of the major causes of the imbalance of mineral metabolism in hepatic fibrosis and further aggravation of the disease.

Actions and beliefs related to hepatitis B and influenza immunization among registered nurses in Texas.

PubMed

McEwen, Melanie; Farren, Elizabeth

2005-01-01

Studies indicate that roughly half of health care workers are not immunized against hepatitis B and influenza. Findings from a survey of 1,000 registered nurses (RNs) conducted to analyze their beliefs and actions related to immunization recommendations are reported. Only 8% of the responding RNs chose not to receive vaccination against hepatitis B. The primary reasons that nurses declined hepatitis B vaccination were because they were not working in nursing or did not believe they were at risk of exposure. Similarly, 86% of the RNs reported they had ever received a flu shot, and 69% reported of being immunized during 2 of the previous 4 years. Rationale for receiving immunization included belief in its effectiveness, belief that they were at risk of exposure, and that it was provided free of charge. Reasons for declining included concerns about side effects, lack of concern about getting the illness, and doubts about effectiveness. The nurses who responded to the survey appear to value immunizations and generally adhere to immunization recommendations. Further study needs to be conducted on related issues, including follow-up for assessment of long-term protection of hepatitis B immunization and adherence to guidelines for postexposure prophylaxis. Ongoing monitoring and further study of serious complications of hepatitis B immunizations are also needed.

Using mummichog (Fundulus heteroclitus) arrays to monitor the effectiveness of remediation at a superfund site in Charleston, South Carolina, U.S.A.

PubMed

Roling, Jonathan A; Bain, Lisa J; Gardea-Torresdey, Jorge; Key, Peter B; Baldwin, William S

2007-06-01

We previously developed a cDNA array for mummichogs (Fundulus heteroclitus), an estuarine minnow, that is targeted for identifying differentially expressed genes from exposure to polycyclic aromatic hydrocarbons and several metals, including chromium. A chromium-contaminated Superfund site at Shipyard Creek in Charleston, South Carolina, USA, is undergoing remediation, providing us a unique opportunity to study the utility of arrays for monitoring the effectiveness of site remediation. Mummichogs were captured in Shipyard Creek in Charleston prior to remediation (2000) and after remediation began (2003 and 2005). Simultaneously, mummichogs were collected from a reference site at the Winyah Bay National Estuarine Research Reserve (NERR) in Georgetown, South Carolina, USA. The hepatic gene expression pattern of fish captured at Shipyard Creek in 2000 showed wide differences from the fish captured at NERR in 2000. Interestingly, as remediation progressed the gene expression pattern of mummichogs captured at Shipyard Creek became increasingly similar to those captured at NERR. The arrays acted as multidimensional biomarkers as the number of differentially expressed genes dropped from 22 in 2000 to four in 2003, and the magnitude of differential expression dropped from 3.2-fold in 2000 to no gene demonstrating a difference over 1.5-fold in 2003. Furthermore, the arrays indicated changes in the bioavailability of chromium caused by hydraulic dredging in the summer of 2005. This research is, to our knowledge, the first report using arrays as biomarkers for a weight-of-evidence hazard assessment and demonstrates that arrays can be used as multidimensional biomarkers to monitor site mitigation because the gene expression profile is associated with chromium bioavailability and body burden.

Combined etiology for bilateral and simultaneous optic neuropathy in a patient with ciancobalamin deficit and hepatitis C treated with peg-interferon and ribavirin.

PubMed

Pantalon, Anca Delia; Danielescu, Ciprian; Chiseliță, Dorin

2016-01-01

We report the case of a 53-year-old female patient who developed bilateral sudden visual acuity loss after 15 weeks from the initiation of Peg-Interferon and Ribavirin treatment for hepatitis C. Debut was simultaneous and asymmetric, reported in the morning, at awakening. No pain or other symptom was reported by the patient. Results. At presentation, visual acuity was 0.2 in RE and 3/ 50 in LE. Pupillary reflexes were sluggish and severe dyschromatopsia was documented in both eyes (Ishihara plates). Fundus examination revealed bilateral pale optic disc edema, more prominent in LE, with splinter hemorrhages in the RNFL around the optic disk. Visual field exam demonstrated severe defects in 3 quadrants of the RE, whereas in the LE, it was impossible to perform the investigation due to VA<0.1. Neurologic evaluation was normal; other possible causes of systemic vasculitis were excluded by negative lab tests. Acute inflammatory markers (fibrinogen and ESR) and mild pancytopenia were the only documented laboratory changes in this patient. Anamnesis cleared the traditional risk factors for conventional AION (hypertension, diabetes, ischemic heart disease, and hypercholesterolemia). Cranial and orbital CT scan and MRI findings were normal. Patient was withdrawn from the Interferon and Ribavirin treatment and was administered methyl prednisolone pulse therapy (1g/ day) for 3 days, continued with oral Prednisone (60 mg/ day) tapered slowly for over 12 weeks. VA increased to 0.8 during treatment in the RE, but visual recovery in the LE was not as spectacular (0.16) as in the fellow eye. Modified latencies and amplitudes in evoked visual potentials examination during 4 months time emphasized bilateral optic atrophy. Optic nerve sufferance was amplified by a low level of vitamin B12, detected by chance at the last eye visit. Due to the general condition, dietary supplementation was not possible. Conclusion. A case of a patient with bilateral and simultaneous NAION caused by IFN and Ribavirin treatment for hepatitis C, who was also vitamin B12 deficient, was analyzed. Therefore, a combined etiology for optic atrophy was explained.

Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility—Virginia, 2010

PubMed Central

Bender, Thomas John; Sharapov, Umid; Utah, Okey; Xing, Jian; Hu, Dale; Rybczynska, Jolanta; Drobeniuc, Jan; Kamili, Saleem; Spradling, Philip R.; Moorman, Anne C.

2017-01-01

Background Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF (“Facility X”) where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response. Methods Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX™ (GSK) given at 0, 1, and 7 months. Blood samples were collected 1–2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs). Results Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10 mIU/mL. Neither age nor neuropsychiatric comorbidity was a significant determinant of seroprotection. Geometric mean concentration was lower among residents aged 60–74 years (74.3 mIU/mL) than among residents aged 46–59 years (105.3 mIU/mL) but highest among residents aged ≥75 years (122.5 mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation. Conclusions Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs. PMID:24370706

The effect of enteric galactose on neonatal canine carbohydrate metabolism

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

Kliegman, R.M.; Miettinen, E.L.; Kalhan, S.C.

1981-01-01

Newborn pups were assigned to a fasting group or to a group receiving intravenous glucose alimentation. Glucose turnover was determined during steady state equilibration of simultaneously infused (6-/sup 3/H) glucose. Thereafter, pups from each group received 0.625 g/Kg of either oral (U-/sup 14/C) galactose or (U-/sup 14/C) glucose. In fasted or intravenously alimented pups enteric glucose resulted in a rapid and sustained elevation of blood glucose concentrations. Systemic appearance of /sup 14/C label from enteric glucose increased rapidly as did the enrichment of blood (/sup 14/C) glucose specific activity. In those pups given enteric galactose, blood glucose values were equivalentmore » to that in the glucose fed groups, however /sup 14/C appearing in blood glucose and blood glucose specific activity was significantly lower. The peak values for rates of appearance and disappearance of systemic glucose were significantly lower in pups fed galactose than among pups fed glucose. Glucose clearance was also significantly lower in these pups despite equivalent plasma insulin responses. Among fasting pups hepatic glycogen content was significantly higher in those given either oral glucose or galactose when compared to a completely starved control group. In contrast, among alimented pups galactose administration significantly enhanced hepatic glycogen content compared to those fed glucose. In addition, hepatic glycogen synthase (glucose-6-phosphate independent) activity was increased only among alimented pups fed galactose when compared to completely fasted pups. In conclusion these data suggest that following gastrointestinal galactose administration, hepatic carbohydrate uptake is augmented while glycogen synthesis may be enhanced. Augmented glycogen synthesis following galactose administration may reflect alterations in hepatic glycogen synthase activity or enhanced hepatic carbohydrate uptake.« less

Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models.

PubMed

Varma, Manthena V; El-Kattan, Ayman F

2016-07-01

A large body of evidence suggests hepatic uptake transporters, organic anion-transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. © 2016, The American College of Clinical Pharmacology.

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

PubMed

Diana, Michele; Liu, Yu-Yin; Pop, Raoul; Kong, Seong-Ho; Legnèr, Andras; Beaujeux, Remy; Pessaux, Patrick; Soler, Luc; Mutter, Didier; Dallemagne, Bernard; Marescaux, Jacques

2017-03-01

Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego ® , multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Applications of minimal physiologically-based pharmacokinetic models

PubMed Central

Cao, Yanguang

2012-01-01

Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available. Such models depend on the quality of the drug disposition data and have vague biological features. An alternative minimal-physiologically-based PK (minimal-PBPK) modeling approach is proposed which inherits and lumps major physiologic attributes from whole-body PBPK models. The body and model are represented as actual blood and tissue usually total body weight) volumes, fractions (fd) of cardiac output with Fick’s Law of Perfusion, tissue/blood partitioning (Kp), and systemic or intrinsic clearance. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologically-relevant PK parameters which are more easily interpreted than those from mam-millary models. The minimal-PBPK models were applied to four types of therapeutic agents and conditions. The models well captured the human PK profiles of 22 selected beta-lactam antibiotics allowing comparison of fitted and calculated Kp values. Adding a classical hepatic compartment with hepatic blood flow allowed joint fitting of oral and intravenous (IV) data for four hepatic elimination drugs (dihydrocodeine, verapamil, repaglinide, midazolam) providing separate estimates of hepatic intrinsic clearance, non-hepatic clearance, and pre-hepatic bioavailability. The basic model was integrated with allometric scaling principles to simultaneously describe moxifloxacin PK in five species with common Kp and fd values. A basic model assigning clearance to the tissue compartment well characterized plasma concentrations of six monoclonal antibodies in human subjects, providing good concordance of predictions with expected tissue kinetics. The proposed minimal-PBPK modeling approach offers an alternative and more rational basis for assessing PK than compartmental models. PMID:23179857

Occult Hepatitis B (OBH) in Clinical Settings

PubMed Central

Alavian, Seyed Moayed; Miri, Seyed Mohammad; Hollinger, F. Blaine; Jazayeri, Seyed Mohammad

2012-01-01

Context Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to summarize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. Evidence Acquisition OHB could be found in different population and clinical backgrounds including: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters. Results The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and hepatocellular carcinoma development remains unknown. Conclusions Monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection. PMID:23087749

Simultaneous monitoring technique for ASE and MPI noises in distributed Raman Amplified Systems.

PubMed

Choi, H Y; Jun, S B; Shin, S K; Chung, Y C

2007-07-09

We develop a new technique for simultaneously monitoring the amplified spontaneous emission (ASE) and multi-path interference (MPI) noises in distributed Raman amplified (DRA) systems. This technique utilizes the facts that the degree-of polarization (DOP) of the MPI noise is 1/9, while the ASE noise is unpolarized. The results show that the proposed technique can accurately monitor both of these noises regardless of the bit rates, modulation formats, and optical signal-to-noise ratio (OSNR) levels of the signals.

Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism.

PubMed

Shin, Andrew C; Zheng, Huiyuan; Berthoud, Hans-Rudolf

2012-02-01

To determine the role of the common hepatic branch of the abdominal vagus on the beneficial effects of Roux-en-Y gastric bypass (RYGB) on weight loss, food intake, food choice, and energy expenditure in a rat model. Although changes in gut hormone patterns are the leading candidates in RYGB's effects on appetite, weight loss, and reversal of diabetes, a potential role for afferent signaling through the vagal hepatic branch potentially sensing glucose levels in the hepatic portal vein has recently been suggested in a mouse model of RYGB. Male Sprague-Dawley rats underwent either RYGB alone (RYGB; n = 7), RYGB + common hepatic branch vagotomy (RYGB + HV; n = 6), or sham procedure (sham; n = 9). Body weight, body composition, meal patterns, food choice, energy expenditure, and fecal energy loss were monitored up to 3 months after intervention. Both RYGB and RYGB + HV significantly reduced body weight, adiposity, meal size, and fat preference, and increased satiety, energy expenditure, and respiratory exchange rate compared with sham procedure, and there were no significant differences in these effects between RYGB and RYGB + HV rats. Integrity of vagal nerve supply to the liver, hepatic portal vein, and the proximal duodenum provided by the common hepatic branch is not necessary for RYGB to reduce food intake and body weight or increase energy expenditure. Specifically, it is unlikely that a hepatic portal vein glucose sensor signaling RYGB-induced increased intestinal gluconeogenesis to the brain depends on vagal afferent fibers.

Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder.

PubMed

Wanmuang, Harirak; Leopairut, Juvady; Kositchaiwat, Chomsri; Wananukul, Winai; Bunyaratvej, Sukhum

2007-01-01

Hepatotoxic effect related to Ganoderma lucidum (Lingzhi) mushroom powder was first described in a patient from Hong Kong in 2004. In 2005, the authors experienced a case of fatal fulminant hepatitis associated with such a preparation. Both patients had taken other therapeutic agents and traditionally boiled Lingzhi without any toxic effect. After switching to taking Lingzhi in powder form for 1-2 months, the hepatotoxic episode occurred in both patients. The toxic role of Lingzhi powder needs close monitoring in the future, especially in combination with other drugs.

Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C

PubMed Central

Wilson, Eleanor M.; Rosenthal, Elana S.; Kattakuzhy, Sarah; Tang, Lydia

2016-01-01

SUMMARY Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors. PMID:27795306

Clinical Application of Vibration Controlled Transient Elastography in Patients with Chronic Hepatitis B

PubMed Central

Liang, Xie-Er; Chen, Yong-Peng

2017-01-01

Abstract Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B. Due to the limitation of liver biopsy, non-invasive methods, especially liver stiffness measurement (LSM) by vibration controlled transient elastography, have been developed and widely applied for liver fibrosis assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in monitoring treatment response, its applications in prediction of liver complications in terms of portal hypertension and esophageal varices, as well as disease prognosis, have been gradually validated. Here, we review the latest clinical applications of LSM in patients with chronic hepatitis B. PMID:29226103

Long-term microfluidic glucose and lactate monitoring in hepatic cell culture

PubMed Central

Prill, Sebastian; Jaeger, Magnus S.; Duschl, Claus

2014-01-01

Monitoring cellular bioenergetic pathways provides the basis for a detailed understanding of the physiological state of a cell culture. Therefore, it is widely used as a tool amongst others in the field of in vitro toxicology. The resulting metabolic information allows for performing in vitro toxicology assays for assessing drug-induced toxicity. In this study, we demonstrate the value of a microsystem for the fully automated detection of drug-induced changes in cellular viability by continuous monitoring of the metabolic activity over several days. To this end, glucose consumption and lactate secretion of a hepatic tumor cell line were continuously measured using microfluidically addressed electrochemical sensors. Adapting enzyme-based electrochemical flat-plate sensors, originally designed for human whole-blood samples, to their use with cell culture medium supersedes the common manual and laborious colorimetric assays and off-line operated external measurement systems. The cells were exposed to different concentrations of the mitochondrial inhibitor rotenone and the cellular response was analyzed by detecting changes in the rates of the glucose and lactate metabolism. Thus, the system provides real-time information on drug-induced liver injury in vitro. PMID:24926387

High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

PubMed

Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-08-01

Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

High Phenobarbital Clearance During Continuous Renal Replacement Therapy

PubMed Central

Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-01-01

Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns or compromising the immune responses to any of the vaccine antigens. [NCT01453348]. © 2014 International Society of Travel Medicine.

PPARα/γ antagonists reverse the ameliorative effects of osthole on hepatic lipid metabolism and inflammatory response in steatohepatitic rats.

PubMed

Zhao, Xi; Wang, Feng; Zhou, Ruijun; Zhu, Zengyan; Xie, Meilin

2018-04-01

Our previous studies have indicated that osthole may ameliorate the hepatic lipid metabolism and inflammatory response in nonalcoholic steatohepatitic rats, but the underlying mechanisms remain unclear. This study aimed to determine whether the effects of osthole were mediated by the activation of hepatic peroxisome proliferator-activated receptor α/γ (PPARα/γ). A rat model with steatohepatitis was induced by orally feeding high-fat and high-sucrose emulsion for 6 weeks. These experimental rats were then treated with osthole (20 mg/kg), PPARα antagonist MK886 (1 mg/kg) plus osthole (20 mg/kg), PPARγ antagonist GW9662 (1 mg/kg) plus osthole (20 mg/kg) and MK886 (1 mg/kg) plus GW9662 (1 mg/kg) plus osthole (20 mg/kg) for 4 weeks. The results showed that after osthole treatment, the hepatic triglycerides, free fatty acids, tumor necrosis factor-α, monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-8 and liver index decreased by 52.3, 31.0, 32.4, 28.9, 36.3, 29.3 and 29.9%, respectively, and the score of steatohepatitis also decreased by 70.0%, indicating that osthole improved the hepatic steatosis and inflammation. However, these effects of osthole were reduced or abrogated after simultaneous addition of the specific PPARα antagonist MK886 or/and the PPARγ antagonist GW9662, especially in the co-PPARα/γ antagonists-treated group. Importantly, the osthole-induced hepatic expressions of PPARα/γ proteins were decreased, and the osthole-regulated hepatic expressions of lipogenic and inflammatory gene proteins were also reversed by PPARα/γ antagonist treatment. These findings demonstrated that the ameliorative effect of osthole on nonalcoholic steatohepatitis was mediated by PPARα/γ activation, and osthole might be a natural dual PPARα/γ activator.

Enhanced mucosal immune responses induced by a combined candidate mucosal vaccine based on Hepatitis A virus and Hepatitis E virus structural proteins linked to tuftsin.

PubMed

Gao, Yan; Su, Qiudong; Yi, Yao; Jia, Zhiyuan; Wang, Hao; Lu, Xuexin; Qiu, Feng; Bi, Shengli

2015-01-01

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are the most common causes of infectious hepatitis. These viruses are spread largely by the fecal-oral route and lead to clinically important disease in developing countries. To evaluate the potential of targeting hepatitis A and E infection simultaneously, a combined mucosal candidate vaccine was developed with the partial open reading frame 2 (ORF2) sequence (aa 368-607) of HEV (HE-ORF2) and partial virus protein 1 (VP1) sequence (aa 1-198) of HAV (HA-VP1), which included the viral neutralization epitopes. Tuftsin is an immunostimulatory peptide which can enhance the immunogenicity of a protein by targeting it to macrophages and dendritic cells. Here, we developed a novel combined protein vaccine by conjugating tuftsin to HE-ORF2 and HA-VP1 and used synthetic CpG oligodeoxynucleotides (ODNs) as the adjuvant. Subsequent experiments in BALB/c mice demonstrated that tuftsin enhanced the serum-specific IgG and IgA antibodies against HEV and HAV at the intestinal, vaginal and pulmonary interface when delivered intranasally. Moreover, mice from the intranasally immunized tuftsin group (HE-ORF2-tuftsin + HA-VP1-tuftsin + CpG) showed higher levels of IFN-γ-secreting splenocytes (Th1 response) and ratio of CD4+/CD8+ T cells than those of the no-tuftsin group (HE-ORF2 + HA-VP1 + CpG). Thus, the tuftsin group generated stronger humoral and cellular immune responses compared with the no-tuftsin group. Moreover, enhanced responses to the combined protein vaccine were obtained by intranasal immunization compared with intramuscular injection. By integrating HE-ORF2, HA-VP1 and tuftsin in a vaccine, this study validated an important concept for further development of a combined mucosal vaccine against hepatitis A and E infection.

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

PubMed Central

2011-01-01

Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

Serologic and ultrasonographic parameters of praziquantel treatment of hepatic fibrosis in Schistosoma japonicum infection.

PubMed

Ohmae, H; Tanaka, M; Nara, T; Utsunomiya, H; Taguchi, H; Irie, Y; Yasuraoka, K

1991-09-01

We describe the parameters useful in evaluating the development of hepatic fibrosis in Schistosoma japonicum infection, as well as its improvement after treatment with praziquantel (PZQ). Various serologic parameters and ultrasonographic images were examined, and their changes were monitored using rabbits infected with 200 or 300 cercariae of S. japonicum. Infected rabbits were administered one oral treatment of PZQ at a dosage of 100 mg/kg at 6, 12, or 24 weeks after infection. Histopathologic examinations revealed that PZQ had a strong and rapid effect, even on damage that developed long after the infection. The improvement of moderate hepatic fibrosis that developed over 24 weeks after infection was also detected by histopathologic examinations. The serum level of total bile acid was the most sensitive parameter in evaluating the severity of hepatic fibrosis and its improvement after treatment with PZQ. The level of serum procollagen-III-peptide was also useful in evaluating the development of hepatic fibrosis, but not in its improvement. Ultrasonography revealed specific echogenic bands and nodules according to the progress of granuloma formation and fibrosis, and the reversal of these changes could also be observed after treatment with PZQ.

Trauma surgeons practice what they preach: The NTDB story on solid organ injury management.

PubMed

Hurtuk, Michael; Reed, R Lawrence; Esposito, Thomas J; Davis, Kimberly A; Luchette, Fred A

2006-08-01

Recent studies advocate a nonoperative approach for hepatic and splenic trauma. The purpose of this study was to determine whether the literature has impacted surgical practice and, if so, whether or not the overall mortality of these injuries had changed. The American College of Surgeons' National Trauma Data Bank (NTDB 4.0) was analyzed using trauma admission dates ranging from 1994 to 2003. All hepatic and splenic injuries were identified by ICD-9 codes. As renal trauma management has not changed during the study period, renal injuries were included as a control. Nonoperative management (NOM) rates and overall mortality were determined for each organ. Proportions were compared using chi analysis with significance set at p < 0.05. There were 87,237 solid abdominal organ injuries reported and included: 35,767 splenic, 35,510 hepatic, 15,960 renal injuries. There was a significant (p < 0.00000000005) increase in percentage of NOM for hepatic and splenic trauma whereas renal NOM remained stable for the study period. Despite an increase in NOM for splenic and hepatic injuries, mortality has remained unchanged. This study demonstrates that the management of hepatic and splenic injuries has significantly changed in the past 10 years with no appreciable effect on mortality. NOM has become the standard of care for the management of hepatic and splenic trauma. The NTDB can be used to monitor changes in trauma care in response to new knowledge regarding improved outcomes.

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies. PMID:27605883

Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension.

PubMed

Frydrychowicz, A; Roldan-Alzate, A; Winslow, E; Consigny, D; Campo, C A; Motosugi, U; Johnson, K M; Wieben, O; Reeder, S B

2017-12-01

Objectives of this study were to compare radial time-resolved phase contrast magnetic resonance imaging (4D Flow-MRI) with perivascular ultrasound (pvUS) and to explore a porcine model of acute pre-hepatic portal hypertension (PHTN). Abdominal 4D Flow-MRI and pvUS in portal and splenic vein, hepatic and both renal arteries were performed in 13 pigs of approximately 60 kg. In six pigs, measurements were repeated after partial portal vein (PV) ligature. Inter- and intra-reader comparisons and statistical analysis including Bland-Altman (BA) comparison, paired Student's t tests and linear regression were performed. PvUS and 4D Flow-MRI measurements agreed well; flow before partial PV ligature was 322 ± 30 ml/min in pvUS and 297 ± 27 ml/min in MRI (p = 0.294), and average BA difference was 25 ml/min [-322; 372]. Inter- and intra-reader results differed very little, revealed excellent correlation (R 2  = 0.98 and 0.99, respectively) and resulted in BA differences of -5 ml/min [-161; 150] and -2 ml/min [-28; 25], respectively. After PV ligature, PV flow decreased from 356 ± 50 to 298 ± 61 ml/min (p = 0.02), and hepatic arterial flow increased from 277 ± 36 to 331 ± 65 ml/min (p = n.s.). The successful in vivo comparison of radial 4D Flow-MRI to perivascular ultrasound revealed good agreement of abdominal blood flow although with considerable spread of results. A model of pre-hepatic PHTN was successfully introduced and acute responses monitored. • Radial 4D Flow-MRI in the abdomen was successfully compared to perivascular ultrasound. • Inter- and intra-reader testing demonstrated excellent reproducibility of upper abdominal 4D Flow-MRI. • A porcine model of acute pre-hepatic portal hypertension was successfully introduced. • 4D Flow-MRI successfully monitored acute changes in a model of portal hypertension.

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

PubMed

Mohamed, T; Oikawa, S; Iwasaki, Y; Mizunuma, Y; Takehana, K; Endoh, D; Kurosawa, T; Sato, H

2004-04-01

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P < 0.01). In the liver, the hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

Comparative Effects of Dexmedetomidine and Propofol on US-Guided Radiofrequency Ablation of Hepatic Neoplasm Under Monitored Anesthesia Care

PubMed Central

Joung, Kyoung-Woon; Choi, Seong-Soo; Jang, Dong-Min; Kong, Yu-Gyeong; Lee, Hwa-Mi; Shim, Ji-Hoon; Won, Hyung-Jin; Shin, Yong-Moon; Kim, Pyo-Nyun; Song, Myung-Hee

2015-01-01

Abstract Percutaneous radiofrequency ablation (RFA) is a useful and safe procedure for treating hepatic neoplasm. However, liver RFA causes severe pain, which thereby increases the demand for monitored anesthesia care (MAC). Here, we compared the efficacy and safety of propofol and dexmedetomidine, which are commonly administered during MAC when performing RFA to assess hepatic neoplasm. In this randomized controlled trial, 40 patients were randomly allocated to 2 groups for elective RFA. Patients received either dexmedetomidine (group D) or propofol (group P). Both groups received the continuous infusion of remifentanil for pain control. The primary outcomes were opioid consumption and differences in partial pressure of arterial carbon dioxide (PaCO2) between pre- and postprocedure RFA. In addition, hemodynamic parameters, patient satisfaction, and interventional radiologist satisfaction were determined. There were significant differences in opioid consumption (50.1 ± 16.8 ng/kg/min [group D] vs 71.2 ± 18.7 ng/kg/min [group P]; P = 0.001) and delta PaCO2 (10.4 ± 6.4 mm Hg vs 17.2 ± 9.2 mm Hg, respectively; P = 0.016). Moreover, respiratory rates were significantly different between groups during RFA (P < 0.001). However, blood pressure and heart rate did not significantly change during RFA. Neither patient nor interventional radiologist satisfaction was significantly different between groups. Dexmedetomidine provides better respiratory stability and reduces opioid consumption in comparison with propofol when administered under MAC when performing RFA for hepatic neoplasm. PMID:26266387

Gaps in the prevention of perinatal transmission of hepatitis B virus between recommendations and routine practices in a highly endemic region: a provincial population-based study in China.

PubMed

Hu, Yali; Zhang, Shu; Luo, Chao; Liu, Qilan; Zhou, Yi-Hua

2012-09-17

Hepatitis B virus (HBV) infection is endemic in China; perinatal transmission is the main source of chronic HBV infection. Simultaneous administration of hepatitis B immune globulin (HBIG) and hepatitis B vaccine is highly effective to prevent perinatal transmission of HBV; however, the effectiveness also depends on full adherence to the recommended protocols in daily practice. In the present investigation, we aimed to identify gaps in immunoprophylaxis of perinatal transmission of HBV between recommendations and routine practices in Jiangsu Province, China. Totally 626 children from 6 cities and 8 rural areas across Jiangsu Province, China, born from February 2003 to December 2004, were enrolled; 298 were born to mothers with positive hepatitis B surface antigen (HBsAg) and 328 were born to HBsAg-negative mothers. Immunoprophylactic measures against hepatitis B were retrospectively reviewed for about half of the children by checking medical records or vaccination cards and the vaccine status was validated for most of children. Of 298 children born to HBV carrier mothers, 11 (3.7%) were HBsAg positive, while none of 328 children born to non-carrier mothers was HBsAg positive (P < 0.01). The rates of anti-HBs ≥ 10 mIU/ml in children of carrier and non-carrier mothers were 69.5% and 69.2% respectively (P = 0.95). The hepatitis B vaccine coverage in two groups was 100% and 99.4% respectively (P = 0.50), but 15.1% of HBV-exposed infants did not receive the timely birth dose. Prenatal HBsAg screening was performed only in 156 (52.3%) of the carrier mothers. Consequently, only 112 (37.6%) of HBV-exposed infants received HBIG after birth. Furthermore, of the 11 HBV-infected children, only one received both HBIG and hepatitis B vaccine timely, seven missed HBIG, two received delayed vaccination, and one missed HBIG and received delayed vaccination. There are substantial gaps in the prevention of perinatal HBV infection between the recommendations and routine practices in China, which highlights the importance of full adherence to the recommendations to eliminate perinatal HBV infection in the endemic regions.

Hepatic venous pressure gradient after portal vein embolization: An accurate predictor of future liver remnant hypertrophy.

PubMed

Mohkam, Kayvan; Rode, Agnès; Darnis, Benjamin; Manichon, Anne-Frédérique; Boussel, Loïc; Ducerf, Christian; Merle, Philippe; Lesurtel, Mickaël; Mabrut, Jean-Yves

2018-05-09

The impact of portal hemodynamic variations after portal vein embolization on liver regeneration remains unknown. We studied the correlation between the parameters of hepatic venous pressure measured before and after portal vein embolization and future hypertrophy of the liver remnant after portal vein embolization. Between 2014 and 2017, we reviewed patients who were eligible for major hepatectomy and who had portal vein embolization. Patients had undergone simultaneous measurement of portal venous pressure and hepatic venous pressure gradient before and after portal vein embolization by direct puncture of portal vein and inferior vena cava. We assessed these parameters to predict future liver remnant hypertrophy. Twenty-six patients were included. After portal vein embolization, median portal venous pressure (range) increased from 15 (9-24) to 19 (10-27) mm Hg and hepatic venous pressure gradient increased from 5 (0-12) to 8 (0-14) mm Hg. Median future liver remnant volume (range) was 513 (299-933) mL before portal vein embolization versus 724 (499-1279) mL 3 weeks after portal vein embolization, representing a 35% (7.4-83.6) median hypertrophy. Post-portal vein embolization hepatic venous pressure gradient was the most accurate parameter to predict failure of future liver remnant to reach a 30% hypertrophy (c-statistic: 0.882 [95% CI: 0.727-1.000], P < 0.001). A cut-off value of post-portal vein embolization hepatic venous pressure gradient of 8 mm Hg showed a sensitivity of 91% (95% CI: 57%-99%), specificity of 80% (95% CI: 52%-96%), positive predictive value of 77% (95% CI: 46%-95%) and negative predictive value of 92.3% (95% CI: 64.0%-99.8%). On multivariate analysis, post-portal vein embolization hepatic venous pressure gradient and previous chemotherapy were identified as predictors of impaired future liver remnant hypertrophy. Post-portal vein embolization hepatic venous pressure gradient is a simple and reproducible tool which accurately predicts future liver remnant hypertrophy after portal vein embolization and allows early detection of patients who may benefit from more aggressive procedures inducing future liver remnant hypertrophy. (Surgery 2018;143:1-2.). Copyright © 2018 Elsevier Inc. All rights reserved.

Hepatitis C in pregnancy: screening, treatment, and management.

PubMed

Hughes, Brenna L; Page, Charlotte M; Kuller, Jeffrey A

2017-11-01

In the United States, 1-2.5% of pregnant women are infected with hepatitis C virus, which carries an approximately 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence regarding hepatitis C virus in pregnancy and to provide recommendations on screening, treatment, and management of this disease during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations: (1) We recommend that obstetric care providers screen women who are at increased risk for hepatitis C infection by testing for anti-hepatitis C virus antibodies at their first prenatal visit. If initial results are negative, hepatitis C screening should be repeated later in pregnancy in women with persistent or new risk factors for hepatitis C infection (eg, new or ongoing use of injected or intranasal illicit drugs) (GRADE 1B). (2) We recommend that obstetric care providers screen hepatitis C virus-positive pregnant women for other sexually transmitted diseases, including HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 1B). (3) We suggest that patients with hepatitis C virus, including pregnant women, be counseled to abstain from alcohol (Best Practice). (4) We recommend that direct-acting antiviral regimens only be used in the setting of a clinical trial or that antiviral treatment be deferred to the postpartum period as direct-acting antiviral regimens are not currently approved for use in pregnancy (GRADE 1C). (5) We suggest that if invasive prenatal diagnostic testing is requested, women be counseled that data on the risk of vertical transmission are reassuring but limited; amniocentesis is recommended over chorionic villus sampling given the lack of data on the latter (GRADE 2C). (6) We recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B). (7) We recommend that obstetric care providers avoid internal fetal monitoring, prolonged rupture of membranes, and episiotomy in managing labor in hepatitis C virus-positive women (GRADE 1B). (8) We recommend that providers not discourage breast-feeding based on a positive hepatitis C virus infection status (GRADE 1A). Copyright © 2017 Elsevier Inc. All rights reserved.

Breath acetone to monitor life style interventions in field conditions: an exploratory study.

PubMed

Samudrala, Devasena; Lammers, Gerwen; Mandon, Julien; Blanchet, Lionel; Schreuder, Tim H A; Hopman, Maria T; Harren, Frans J M; Tappy, Luc; Cristescu, Simona M

2014-04-01

To assess whether breath acetone concentration can be used to monitor the effects of a prolonged physical activity on whole body lipolysis and hepatic ketogenesis in field conditions. Twenty-three non-diabetic, 11 type 1 diabetic, and 17 type 2 diabetic subjects provided breath and blood samples for this study. Samples were collected during the International Four Days Marches, in the Netherlands. For each participant, breath acetone concentration was measured using proton transfer reaction ion trap mass spectrometry, before and after a 30-50 km walk on four consecutive days. Blood non-esterified free fatty acid (NEFA), beta-hydroxybutyrate (BOHB), and glucose concentrations were measured after walking. Breath acetone concentration was significantly higher after than before walking, and was positively correlated with blood NEFA and BOHB concentrations. The effect of walking on breath acetone concentration was repeatedly observed on all four consecutive days. Breath acetone concentrations were higher in type 1 diabetic subjects and lower in type 2 diabetic subjects than in control subjects. Breath acetone can be used to monitor hepatic ketogenesis during walking under field conditions. It may, therefore, provide real-time information on fat burning, which may be of use for monitoring the lifestyle interventions. Copyright © 2014 The Obesity Society.

Wireless Monitoring of Liver Hemodynamics In Vivo

DOE PAGES

Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; ...

2014-07-14

Liver transplants have their highest failure rate in the first two weeks following surgery. There are no devices for continuous, real-time monitoring of the graft, currently. Here, we present a continuous perfusion and oxygen consumption monitor based on photoplethysmography. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two in vivo porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.125 mL/min/g of tissue. We show the possibility of using the pulsatile wave tomore » measure the arterial oxygen saturation similar to pulse oximetry. This signal is used as a feedback to extract the venous oxygen saturation from the DC levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19 and 1.39% respectively when no vascular occlusions were induced. The resulting error increased to 2.82 and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of the oximetry catheter used as a reference. This work is the first realization of a wireless perfusion and oxygenation sensor for continuous monitoring of hepatic perfusion and oxygenation changes.« less

Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen-immortalized mouse hepatic cell line

PubMed Central

Song, Xiu-Guang; Bian, Peng-Fei; Yu, Shu-Li; Zhao, Xiu-Hua; Xu, Wei; Bu, Xue-Hui; Li, Xia; Ma, Li-Xian

2013-01-01

AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression. METHODS: Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively. RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells. HBV DNA replication intermediates were also observed at 72 h after transfection, including relaxed circular DNA, double-stranded DNA and single-stranded DNA. Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles with a spherical or filamentous shape, were detected in the supernatant. CONCLUSION: SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3-transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell model. PMID:24307795

Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen-immortalized mouse hepatic cell line.

PubMed

Song, Xiu-Guang; Bian, Peng-Fei; Yu, Shu-Li; Zhao, Xiu-Hua; Xu, Wei; Bu, Xue-Hui; Li, Xia; Ma, Li-Xian

2013-11-28

To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression. Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively. The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells. HBV DNA replication intermediates were also observed at 72 h after transfection, including relaxed circular DNA, double-stranded DNA and single-stranded DNA. Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles with a spherical or filamentous shape, were detected in the supernatant. SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3-transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell model.

Evaluation of cold chain monitoring in Kelantan, Malaysia.

PubMed

Hanjeet, K; Lye, M S; Sinniah, M; Schnur, A

1996-01-01

An analysis was carried out on a total of 883 cold chain monitor (CCM) cards, which had been attached to batches of poliomyelitis, measles, DPT (diphtheria, pertussis, tetanus) and hepatitis B vaccines, during their transport and storage from the central store in Kuala Lumpur to Kelantan, a state in north-eastern Malaysia; 234 freeze watches attached to hepatitis B vaccines were also analysed. The monitor cards and freeze watches were observed at six levels between the central store and the periphery during distribution of the vaccines, and a colour change in any of the four windows (A, B, C, D) on the CCM cards or the freeze watches was recorded. In addition, 33 unopened vials of oral poliovirus vaccine (OPV), collected from refrigerators in 29 health facilities in Kelantan, were tested for potency using the tissue culture infective dose 50 (TCID50) method; 14 of them (42%) did not meet the WHO criteria for potent vaccines. The results showed that at the final destination 13.4% of all cards remained white while a colour change to blue was observed in 65% in window A, 16.6% in window B, and 4.4% in window C; none had turned blue in window D indicating that the vaccine had not been subjected to temperatures > or = 34 degrees C for 2 hours. All but 2 of the 234 freeze watches had turned purple, which indicates exposure of the hepatitis B vaccines to temperatures below 0 degree C. These results will assist health planners to correct the weaknesses identified in the cold chain system.

Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy.

PubMed

Pradat, P; Chossegros, P; Bailly, F; Pontisso, P; Saracco, G; Sauleda, S; Thursz, M; Tillmann, H; Vlassopoulou, H; Alberti, A; Braconier, J H; Esteban, J I; Hadziyannis, S; Manns, M; Rizzetto, M; Thomas, H C; Trépo, C

2000-05-01

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEXtrade mark bDNA, MONITOR AMPLICORtrade mark and SUPERQUANTtrade mark assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO-LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0. 456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut-offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.

Evaluation of the Potential Risk of Hepatitis B Virus Transmission in Skin Allografting.

PubMed

Wang, D; Xie, W; Chen, T; Dong, C; Zhao, C; Tan, H; Tian, H; Xie, Q

2015-01-01

Skin transplantation is associated with potential risk of infectious disease transmission; however, the exclusion of donors owing to hepatitis B virus (HBV) infection will worsen the shortage of allograft skin supply. We report a paired study to evaluate the potential risk of HBV transmission in skin allografting. The presence of HBV DNA in the serum and skin from 37 burn patients with chronic HBV infection (CHB) was monitored by a HBV polymerase chain reaction (PCR) and the positive rates were compared by Fisher's exact probability test. There was a high consistency in the HBV serology profile between HBV DNA PCR (83.78%) and the clinical HBV test. Only 2 patients who were positive for hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B core antibody had detectable HBV DNA in the skin tissue; however, no hepatitis B surface antigen was detected as examined by immunohistochemistry staining. There was a significant difference between the positive rates of HBV DNA in the serum and skin (χc(2) = 27.03; P < .001). The potential risk for HBV transmission by skin allografting is very low. Given that China has a large population of patients with HBV, the acceptance of skin from donors with CHB to the skin bank would increase the number of tissue donations to meet the urgent medical need for skin transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of disease-associated protein expression using quantitative proteomics—fibulin-5 is expressed in association with hepatic fibrosis.

PubMed

Bracht, Thilo; Schweinsberg, Vincent; Trippler, Martin; Kohl, Michael; Ahrens, Maike; Padden, Juliet; Naboulsi, Wael; Barkovits, Katalin; Megger, Dominik A; Eisenacher, Martin; Borchers, Christoph H; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

2015-05-01

Hepatic fibrosis and cirrhosis are major health problems worldwide. Until now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. To develop noninvasive diagnostic assays for the assessment of liver fibrosis, it is urgently necessary to identify molecules that are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n = 77). Finally, we performed a targeted proteomics approach, multiple reaction monitoring (MRM), to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM), and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.

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

PubMed

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.

Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

PubMed Central

Gill, Katherine L.; Gertz, Michael; Houston, J. Brian

2013-01-01

A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro–in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

Use of Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) to determine hepatic blood flow

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

Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

1984-01-01

Tc-NGA is a new liver radiopharmaceutical which binds to a hepatocyte-specific membrane receptor. Three characteristics of Tc-NGA can be exploited in the measurement of hepatic blood flow (HBF): 1) ability to alter the affinity of Tc-NGA for its receptor by changing the galactose: albumin ratio; 2) ability to achieve a high specific activity with Tc-99m labeling; and 3) ability to administer a high molar dose of Tc-NGA without physiologic side effects. In addition, kinetic modeling of Tc-NGA dynamic data can provide estimates of hepatic receptor concentration. In experimental studies in young pigs, HBF was determined using two techniques: 1) kineticmore » modeling of dynamic data using moderate affinity, low specific activity Tc-NGA (Group A, n=12); and 2) clearance (CL) technique using high affinity, high specific activity Tc-NGA (Group B, n=4). In both groups, HBF was determined simultaneously by continuous infusion of indocyanine green (CI-ICG) with hepatic vein sampling. Regression analysis of HBF measurements obtained with the Tc-NGA kinetic modeling technique and the CI-ICG technique (Group A) revealed good correlation between the two techniques (r=0.802, p=0.02). Similarly, HBF determination by the clearance technique (Group B) provided highly accurate measurements when compared to the CI-ICG technique. Hepatic blood flow measurements by the clearance technique (CL-NGA) fell within one standard deviation of the error associated with each CI-ICG HBF measurement (all CI-ICG standard deviations were less than 10%).« less

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C.

PubMed

Massirer, K B; Hirata, M H; Silva, A E B; Ferraz, M L G; Nguyen, N Y; Hirata, R D C

2004-05-01

Interferon (IFN)-alpha receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-alpha therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-alpha receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-alpha in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFN-alpha 2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-alpha response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcription-polymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/beta-actin-mRNA ratio (mean +/- SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 +/- 0.15; N = 5; P < 0.05) compared to non-responders (0.35 +/- 0.17; N = 12) and controls (0.30 +/- 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in non-responders during IFN-alpha therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-alpha response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

Monitoring Changes in Hepatic Venous Velocities Flow after a Fluid Challenge Can Identify Shock Patients Who Lack Fluid Responsiveness

PubMed Central

Du, Wei; Wang, Xiao-Ting; Long, Yun; Liu, Da-Wei

2017-01-01

Background: Evaluating the hemodynamic status and predicting fluid responsiveness are important in critical ultrasound assessment of shock patients. Transthoracic echocardiography with noninvasive diagnostic parameters allows the assessment of volume responsiveness. This study aimed to assess the hemodynamic changes in the liver and systemic hemodynamic changes during fluid challenge and during passive leg raising (PLR) by measuring hepatic venous flow (HVF) velocity. Methods: This is an open-label study in a tertiary teaching hospital. Shock patients with hypoperfusion who required fluid challenge were selected for the study. Patients <18 years old and those with contraindications to PLR were excluded from the study. Baseline values were measured, PLR tests were performed, and 500 ml of saline was infused over 30 min. Parameters associated with cardiac output (CO) in the left ventricular outflow tract were measured using the Doppler method. In addition, HVF velocity and right ventricular function parameters were determined. Results: Middle hepatic venous (MHV) S-wave velocity was positively correlated in all patients with CO at baseline (r = 0.706, P < 0.01) and after volume expansion (r = 0.524, P = 0.003). CO was also significantly correlated with MHV S-wave velocity in responders (r = 0.608, P < 0.01). During PLR, however, hepatic venous S-wave velocity did not correlate with CO. For the parameter ΔMHV D (increase in change in MHV D-wave velocity after volume expansion), defined as (MHV DafterVE − MHV DBaseline)/MHV DBaseline × 100%, >21% indicated no fluid responsiveness, with a sensitivity of 100%, a specificity of 71.2%, and an area under the receiver operating characteristic curve of 0.918. Conclusions: During fluid expansion, hepatic venous S-wave velocity can be used to monitor CO, whether or not it is increasing. ΔMHV D ≥21% indicated a lack of fluid responsiveness, thus helping to decide when to stop infusions. PMID:28485321

MR-guided microwave ablation in hepatic tumours: initial results in clinical routine.

PubMed

Hoffmann, Rüdiger; Rempp, Hansjörg; Keßler, David-Emanuel; Weiß, Jakob; Pereira, Philippe L; Nikolaou, Konstantin; Clasen, Stephan

2017-04-01

Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years ± 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm ± 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post-ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months ± 2.6 (1-10 months). Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 ± 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ ± 21.7 (9-87 kJ) and 24.7 min ± 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm ± 10.5 (16-65 mm) and 52.7 mm ± 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. • Planning, applicator placement and therapy monitoring are possible without using contrast enhancement • Energy transmission from the generator to the scanner room is safely possible • MR-guided microwave ablation provides effective treatment of hepatic malignancies in one session • Therapy monitoring is possible without applicator retraction from the ablation site.

Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

PubMed Central

Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

2014-01-01

Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ∼70% and ∼20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to steatosis and increased mitochondrial respiration. Onset of this mitochondrial depolarization is linked, at least in part, to metabolism of ethanol to acetaldehyde. PMID:24618581

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

PubMed

Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

2017-04-01

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (P<0.05). Moreover, hepatic total and free cholesterol of CDHF-BCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatitis B Among the Khmer

PubMed Central

Jackson, J Carey; Rhodes, Lorna A; Inui, Thomas S; Buchwald, Dedra

1997-01-01

OBJECTIVE To assess the comprehensibility of hepatitis B translations for Cambodian refugees, to identify Cambodian illnesses that include the symptoms of hepatitis, and to combine these observations with critical theoretical perspectives of language to reflect on the challenges of medical translation generally. DESIGN Open-ended, semistructured interviews, and participant-observation of a refugee community in Seattle, Washington. SETTING Homes of Cambodian residents of inner-city neighborhoods. PARTICIPANTS Thirty-four adult Cambodian refugees who had each been educated about hepatitis B through public health outreach. RESULTS Medical interpreters translated hepatitis B as rauk tlaam, literally “liver disease.” Unfortunately, while everyone knew of the liver (tlaam), rauk tlaam was a meaningless term to 28 (82%) of 34 respondents and conveyed none of the chronicity and communicability intended by refugee health workers for 34 (100%) of the respondents. In contrast, all respondents knew illnesses named after symptom complexes that include the symptoms of acute and chronic hepatitis, but do not refer to diseased organs. The Cambodian words chosen to translate hepatitis B reflect the medical thinking and medical authority that can unintentionally overwhelm attempts at meaningful communication with non–English-speaking patients. CONCLUSIONS To improve comprehension of hepatitis B translations for the Khmer, translators must choose between medical terminology focused on the liver and Khmer terminology which identifies recognizable experiences, but represents important Khmer health concepts. A critical linguistic view of this situation suggests that for these translations to be meaningful clinicians and health educators must first analyze and then monitor the contextual significance of medical language. In cross-cultural settings, this means a partnership with medical interpreters to pay close attention to the expe-rience of illness and social context of the translation. PMID:9159698

Ethnic Disparities in Chronic Hepatitis B Infection: African Americans and Hispanic Americans.

PubMed

Forde, Kimberly A

2017-06-01

Chronic infection with hepatitis B affects more than 240 million persons worldwide and is a major public health concern. Despite national and global initiatives to promote hepatitis B elimination, including newborn vaccination, catch up vaccination in adolescents and high-risk adults, screening of the blood supply and treatment of those in need, both new infections and a reservoir of chronic infections continue to result in morbidity and mortality. As with many chronic diseases, racial and ethnic disparities are seen in hepatitis B virus infection. The goal of this review is to synthesize the data concerning the burden of hepatitis B infection in African Americans and Hispanics, two racial/ethnic groups in the United States who encounter barriers in access to care, low engagement in care and low utilization of diagnostic and treatment services. Recent data, though sparse in certain areas, continue to suggest differences in rates of incidence and prevalence of hepatitis B virus infection in African Americans, and differences in screening, specialty referral and initiation of therapy for African Americans and Hispanics. Data are lacking about differences in liver disease progression and manifestations in both African Americans and Hispanics. Disparities in hepatitis B diagnosis, disease management, treatment and prevention remain for African Americans and Hispanics. These disparities require a commitment from governmental and public health organizations. The efforts should include increasing vaccination in those most susceptible to infection, screening those at highest risk for infection, initiating antiviral therapy in those who require it and monitoring for liver-related complications, such as decompensated cirrhosis and hepatocellular carcinoma in the chronically infected. This multi-pronged approach is necessary to realize hepatitis B elimination.

The effects of booster vaccination on combined hepatitis A and hepatitis B vaccine in both anti-HBs and anti-HAV negative children 5-15 years after hepatitis B vaccine primary immunization.

PubMed

Chen, Yongdi; Gu, Hua; Cheng, Suyun; Shen, Lingzhi; Cui, Fujiang; Wang, Fuzhen; Yao, Jun; Xia, Shichang; Lv, Huakun; Liang, Xiaofeng

2013-04-01

In the present study, we investigated the changes in both anti-HAV lgG and anti-HBs lgG levels and compared the antibody seroconversion rates of different doses of combined hepatitis A and hepatitis B vaccine in children. Children who were vaccinated as infants with Hepatitis B vaccine were revaccinated at 5-15 y of age, then the antibody titers were monitored. Among 283 children, this study found that the anti-HAV seroconversion rates (defined as anti-HAV ≥ 1 mIU/ml) after the first and the third dose were 79.9% and 100% respectively; these observed differences were statistically significant (P<0.05); the corresponding geometric mean titers (GMTs) were 4.72 ± 2.63 mIU/ml and 13.46 ± 1.16 mIU/ml respectively. The anti-HBs seroconversion rates (defined as an anti-HBs ≥ 10 mIU/ml) were 82.3% and 99.0% respectively; these observed differences were statistically significant (P<0.05); and the corresponding titers were 319.95 ± 5.16 mIU/ml and 418.59 ± 3.89 mIU/ml respectively. After the first booster dose, the difference in anti-HAV seroconversion rate was statistically significant in children aged 5-9 y and 10-15 y (P<0.05), as was the difference of anti-HBs seroconversion, whereas after the third dose the difference was not statistically significant (P>0.05). This study demonstrated that the immunization effects of booster vaccination with combined hepatitis A and hepatitis B vaccine is successful for children. A single booster dose is adequate for younger children, while three doses are needed for older children.

Update on hepatitis B and C virus diagnosis

PubMed Central

Villar, Livia Melo; Cruz, Helena Medina; Barbosa, Jakeline Ribeiro; Bezerra, Cristianne Sousa; Portilho, Moyra Machado; Scalioni, Letícia de Paula

2015-01-01

Viral hepatitis B and C virus (HBV and HCV) are responsible for the most of chronic liver disease worldwide and are transmitted by parenteral route, sexual and vertical transmission. One important measure to reduce the burden of these infections is the diagnosis of acute and chronic cases of HBV and HCV. In order to provide an effective diagnosis and monitoring of antiviral treatment, it is important to choose sensitive, rapid, inexpensive, and robust analytical methods. Primary diagnosis of HBV and HCV infection is made by using serological tests for detecting antigens and antibodies against these viruses. In order to confirm primary diagnosis, to quantify viral load, to determine genotypes and resistance mutants for antiviral treatment, qualitative and quantitative molecular tests are used. In this manuscript, we review the current serological and molecular methods for the diagnosis of hepatitis B and C. PMID:26568915

Simple and robust diagnosis of early, small and AFP-negative primary hepatic carcinomas: an integrative approach of serum fluorescence and conventional blood tests.

PubMed

Wang, Ting; Zhang, Kun-He; Hu, Piao-Ping; Huang, Zeng-Yong; Zhang, Pan; Wan, Qin-Si; Huang, De-Qiang; Lv, Nong-Hua

2016-09-27

The diagnosis of early, small and alpha-fetoprotein (AFP)-negative primary hepatic carcinomas (PHCs) remains a significant challenge. We developed a simple and robust approach to noninvasively detect these PHCs. A rapid, high-throughput and single-tube method was firstly developed to measure serum autofluorescence and cell-free DNA (cfDNA)-related fluorescence using a real-time PCR system, and both types of serum fluorescence were measured and routine laboratory data were collected in 1229 subjects, including 353 PHC patients, 331 liver cirrhosis (LC) patients, 213 chronic hepatitis (CH) patients and 332 normal controls (NC). The results showed that fluorescence indicators of PHC differed from those of NC, CH and LC to various extents, and all of them were not associated with age, gender, or AFP level. The logistic regression models established with the fluorescence indicators alone and combined with AFP, hepatic function tests and blood cell analyses were valuable for distinguishing early, small, AFP-negative and all PHC from LC, CH, NC and all non-PHC, with areas under the receiver operating characteristic curves 0.857-0.993 and diagnostic accuracies 80.2-97.7%. Conclusively, serum autofluorescence and cfDNA-related fluorescence are able to be rapidly and simultaneously measured by our simple method and valuable for diagnosing early, small and AFP-negative PHCs, especially integrating with AFP and conventional blood tests.

Direct Detection of Drug-Resistant Hepatitis B Virus in Serum Using a Dendron-Modified Microarray

PubMed Central

Kim, Doo Hyun; Kang, Hong Seok; Hur, Seong-Suk; Sim, Seobo; Ahn, Sung Hyun; Park, Yong Kwang; Park, Eun-Sook; Lee, Ah Ram; Park, Soree; Kwon, So Young; Lee, Jeong-Hoon

2018-01-01

Background/Aims Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. Methods The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. Results The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. Conclusions We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues. PMID:29271185

Value of MRI in three patients with major vascular injuries after laparoscopic cholecystectomy.

PubMed

Ragozzino, Alfonso; Lassandro, Francesco; De Ritis, Rosaria; Imbriaco, Massimo

2007-11-01

The aim of this study was to describe three cases of major vascular injuries after laparoscopic cholecystectomy depicted on magnetic resonance (MR) examination. Three female patients (mean age, 32 years; range, 22-39 years) were studied with clinical suspicion of bilio-vascular injuries after laparoscopic cholecystectomy. All MR examinations were performed within 24 h after the laparoscopic procedure. MR imaging was evaluated for major vascular injuries involving the arterial and portal venous system, for bile duct discontinuity, presence or absence of biliary dilation, stricture, excision injury, free fluid and collections. In the first patient, a type-IV Bismuth injury with associated intrahepatic bile ducts dilation was observed. Contrast-enhanced MR revealed lack of enhancement in the right hepatic lobe due to occlusion of the right hepatic artery and the right portal branch. This patient underwent right hepatectomy with hepatico-jejunostomy. In the other two cases, no visualization of the right hepatic artery and the right portal branch was observed on MR angiography. In the first case, the patient underwent right hepatectomy; in the second case, because of stable liver condition, the patient was managed conservatively. MR imaging combined with MR angiography and MR cholangiography can be performed emergently in patients with suspicion of bilio-vascular injury after laparoscopic cholecystectomy allowing the simultaneous evaluation of the biliary tree and the hepatic vascular supply that is essential for adequate treatment planning.

Saw palmetto-induced pancreatitis.

PubMed

Jibrin, Ismaila; Erinle, Ayodele; Saidi, Abdulfattah; Aliyu, Zakari Y

2006-06-01

Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

Cimetidine and hepatic blood flow in polytrauma patients.

PubMed

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

1985-05-01

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

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

PubMed Central

Sagnelli, Evangelista; Pisaturo, Mariantonietta; Martini, Salvatore; Filippini, Pietro; Sagnelli, Caterina; Coppola, Nicola

2014-01-01

Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI. PMID:25018849

KNOWLEDGE, ATTITUDES AND PRACTICES OF HEPATITIS B AND C AMONG BARBERS OF URBAN AND RURAL AREAS OF RAWALPINDI AND ISLAMABAD.

PubMed

Shah, Hassan Bin Usman; Dar, Mohsin Khalil; Jamil, Anique Ahmad; Atif, Iffat; Ali, Raja Jazib; Sindhu, Ali Shan; Usmani, Abdul Qadir

2015-01-01

Hepatitis B and Hepatitis C are serious global public health problems with a prevalence of 10-15% with majority of the cases seen in the developing countries including Pakistan. It is a blood borne infection transmitted by infected blood and blood products through transfusions, contaminated needles, vertical transmission, unsafe sex and reuse of razors by barbers. The literature search so far did not reveal any study comparing knowledge, attitude and practices of hepatitis B & C in barbers working in Urban and rural areas. A comparative cross sectional survey was carried out among barbers of urban and rural areas of Rawalpindi and Islamabad. A structured close ended questionnaire was filled from total of 202 barbers by non-probability convenience sampling technique. Comparative data analysis was done including variables like age, education, knowledge about hepatitis B & C, mode of transmission, role of the blades and media etc. Knowledge about hepatitis B & C was good in urban areas (92%) as compared to those working in the rural areas (68%). Using new blade for every customer was seen in urban (100%) and rural (93%) area. However barbers knowledge about symptoms of the disease (urban 81% & rural 93%) and vaccination trend of Hepatitis B was low. This study showed a marked difference in the knowledge, attitude and practices of the barbers working in the urban and the rural areas. Main focus should be on launching Health education programs and behaviour change communication campaigns for the barbers. Strict regulatory monitoring must be done against unlicensed street barbers.

Efficacy and Safety of Endovascular Intervention for the Management of Primary Entire-Inferior Vena Cava Occlusion

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

Zhang, Qingqiao, E-mail: 1427286069@qq.com; Huang, Qianxin, E-mail: 18705206105@163.com; Shen, Bin, E-mail: 753021357@qq.com

PurposeThis study was designed to investigate the safety and efficacy of endovascular intervention for the treatment of primary entire-inferior vena cava (IVC) occlusion.MethodsEndovascular interventions were performed in six patients for the treatment of primary entire-IVC occlusion. IVC and hepatic venography were performed via the jugular and femoral veins. Balloon angioplasty was used to revascularize the hepatic vein and IVC and a stent was placed in the IVC to maintain patency. Postoperative color Doppler ultrasonography was performed at 1, 3, 6, and 12 months, and then annually, to monitor the patency of the hepatic vein and IVC.ResultsThe IVC and one or twomore » hepatic veins were successfully revascularized in five patients. Revascularization was successful in the right and left hepatic veins in one patient; however, IVC patency could not be established in this patient. Eleven Z-type, self-expanding stents were placed into the IVCs of five patients (three stents in two patients, two stents in two patients, and one stent in one patient). There were no instances of postoperative bleeding or mortality. Follow-up was conducted for 18–90 months (42.8 ± 26.5 months). None of the five patients suffered restenosis of the IVC or hepatic veins. However, there was one of the six cases of right hepatic vein restenosis at 18 months postprocedure that was revascularized after a second balloon dilatation.ConclusionsEndovascular intervention is safe and efficacious for the treatment of primary entire-IVC occlusion.« less

Single-well monitoring of protein-protein interaction and phosphorylation-dephosphorylation events.

PubMed

Arcand, Mathieu; Roby, Philippe; Bossé, Roger; Lipari, Francesco; Padrós, Jaime; Beaudet, Lucille; Marcil, Alexandre; Dahan, Sophie

2010-04-20

We combined oxygen channeling assays with two distinct chemiluminescent beads to detect simultaneously protein phosphorylation and interaction events that are usually monitored separately. This novel method was tested in the ERK1/2 MAP kinase pathway. It was first used to directly monitor dissociation of MAP kinase ERK2 from MEK1 upon phosphorylation and to evaluate MAP kinase phosphatase (MKP) selectivity and mechanism of action. In addition, MEK1 and ERK2 were probed with an ATP competitor and an allosteric MEK1 inhibitor, which generated distinct phosphorylation-interaction patterns. Simultaneous monitoring of protein-protein interactions and substrate phosphorylation can provide significant mechanistic insight into enzyme activity and small molecule action.

[Is hepatitis E just an imported infection in the Czech Republic?].

PubMed

Haasová, Zdenka; Kleinerová, Jana; Mestáková, Olga

2006-02-01

The article deals with the issue of virus hepatitis E (VHE) whose increased incidence emerged in some Moravian districts in the monitored period from January 2004 to June 2005. The uncoated RNA virus, which is not taxonomically classified at present, is considered to be a causative agent of VHE. In the BIO-PLUS, the company with limited liability, 1 078 sera samples from various hospital and outpatient departments were tested by the ELISA method. The positive IgG and IgM VHE antibodies were found in 24 cases, that corresponded to the clinic condition of patient and to the biochemical findings showing an acute hepatitis. Other virus hepatitis (VHA, VHB, VHC) as well as further hepatotrophic infections were negative in all cases. Until recently the VHE was considered as an imported infection from endemic areas. However, only seven of our 24 positive cases showed a stay abroad, the traveller history was negative in the rest. In our work 18 VHE cases, diagnosed in the infection departments of the hospitals in Breclav and Prostejov, are analysed in details in the referred period.

Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl.

PubMed

Della Corte, Claudia; Carlucci, Antonio; Francalanci, Paola; Alisi, Anna; Nobili, Valerio

2011-06-24

In the last years numerous reports describing a possible association between administration of vaccines and development of autoimmune phenomena and overt autoimmune disease were published. Possible mechanisms of induction of autoimmune phenomena by vaccines and their excipients are probably similar to those implicated in induction by infectious agents. Here we report the case of an 11-year-old girl who developed autoimmune hepatitis type II after four weeks from vaccination against human papillomavirus. The possible relationships between the use of adjuvated vaccine against papillomavirus and autoimmune hepatitis are discussed. Although we do not provide evidence for a causal link, we suggest that the occurrence of the autoimmune hepatitis may be related to the stimulation of immune system by adjuvated-vaccine, that could have triggered the disease in a genetically predisposed individual. Therefore a monitoring of liver function test following administration of vaccine against papillomavirus may be useful in adolescent girl with signs of hepatopathy, as jaundice, dark urine or hepatomegaly, to early identify and to promptly treat autoimmune liver disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides.

PubMed

Peffer, Pasha Lyvers; Lin, Xi; Odle, Jack

2005-06-01

A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel

PubMed Central

Ram, Daniela; Manor, Yossi; Gozlan, Yael; Schwartz, Eli; Ben-Ari, Ziv; Mendelson, Ella; Mor, Orna

2016-01-01

Hepatitis E virus (HEV) is an emerging infectious agent in developed countries. HEV genotypes 1 (G1) and 3 (G3) have been identified in environmental and clinical samples in Europe. In Israel, the overall prevalence of anti-HEV IgG antibodies was found to be 10.6%; however, reports of HEV infection are scarce. In this study, the presence of HEV in Israel was investigated using 169 sewage samples from 32 treatment facilities and 49 samples from acute hepatitis patients, all collected between 2013 and 2015. Fourteen sewage samples, from Haifa (11/18 samples), Tel Aviv (2/29 samples), and Beer Sheva (1/17 samples), regions with good sanitary conditions and middle-high socioeconomic populations, were HEV positive. Among the patient samples, 6.1% (3/49) were HEV positive, all returning travelers from India. Genotype analysis revealed G1 HEV in patients and G3 HEV sequences in sewage. Evidence that HEV could be establishing itself in our region may justify more active surveillance to monitor its spread. PMID:27246446

The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage.

PubMed

Targownik, Laura E; Spiegel, Brennan M R; Dulai, Gareth S; Karsan, Hetal A; Gralnek, Ian M

2004-07-01

Recurrent variceal hemorrhage is common following an initial bleed in patients with cirrhosis. The current standard of care for secondary prophylaxis is endoscopic band ligation (EBL). Combination of beta-blocker and nitrate therapy, guided by hepatic venous pressure gradient (HVPG) monitoring, is a novel alternative strategy. We sought to determine the cost-effectiveness of these competing strategies. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of three competing strategies: (1) EBL; (2) beta-blocker and nitrate therapy without HVPG monitoring (HVPG-); and (3) beta-blocker and nitrate therapy with HVPG monitoring (HVPG+). Patients in the HVPG+ strategy who failed to achieve an HVPG decline from medical therapy were offered EBL. Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per recurrent variceal hemorrhage prevented. Under base-case conditions, the HVPG+ strategy was the most effective yet most expensive approach, followed by EBL and HVPG-. Compared to the EBL strategy, the HVPG+ strategy cost an incremental 5,974 dollars per recurrent bleed prevented. In a population with 100% compliance with all therapies, the incremental cost of HVPG-versus EBL fell to 5,270 dollars per recurrent bleed prevented. The model results were sensitive to the cost of EBL, the cost of HVPG monitoring, and the probability of medical therapy producing an adequate HVPG decline. Compared to EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring is more effective and only marginally more expensive.

Simultaneous real-time monitoring of multiple cortical systems.

PubMed

Gupta, Disha; Jeremy Hill, N; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L; Schalk, Gerwin

2014-10-01

Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main Results: Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic.

Simultaneous Real-Time Monitoring of Multiple Cortical Systems

PubMed Central

Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

2014-01-01

Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic. PMID:25080161

Green light for liver function monitoring using indocyanine green? An overview of current clinical applications.

PubMed

Vos, J J; Wietasch, J K G; Absalom, A R; Hendriks, H G D; Scheeren, T W L

2014-12-01

The dye indocyanine green is familiar to anaesthetists, and has been studied for more than half a century for cardiovascular and hepatic function monitoring. It is still, however, not yet in routine clinical use in anaesthesia and critical care, at least in Europe. This review is intended to provide a critical analysis of the available evidence concerning the indications for clinical measurement of indocyanine green elimination as a diagnostic and prognostic tool in two areas: its role in peri-operative liver function monitoring during major hepatic resection and liver transplantation; and its role in critically ill patients on the intensive care unit, where it is used for prediction of mortality, and for assessment of the severity of acute liver failure or that of intra-abdominal hypertension. Although numerous studies have demonstrated that indocyanine green elimination measurements in these patient populations can provide diagnostic or prognostic information to the clinician, 'hard' evidence - i.e. high-quality prospective randomised controlled trials - is lacking, and therefore it is not yet time to give a green light for use of indocyanine green in routine clinical practice. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

A comparison of two ambulatory blood pressure monitors worn at the same time.

PubMed

Kallem, Radhakrishna R; Meyers, Kevin E C; Sawinski, Deirdre L; Townsend, Raymond R

2013-05-01

There are limited data in the literature comparing two simultaneously worn ambulatory blood pressure (BP) monitoring (ABPM) devices. The authors compared BPs from two monitors (Mobil-O-Graph [I.E.M., Stolberg, Germany] and Spacelabs 90207 [Spacelabs Medical, Issequah, WA]). In the nonrandomized component of the study, simultaneous 8-hour BP and heart rate data were measured by Mobil-O-Graph, consistently applied to the nondominant arm, and Spacelabs to the dominant arm on 12 untreated adults. Simultaneous 8-hour BP and heart data were obtained by the same monitors randomly assigned to a dominant or nondominant arm on 12 other untreated adults. Oscillometric BP profiles were obtained in the dominant and nondominant arms of the above 24 patients using an Accutorr (Datascope, Mahwah, NJ) device. The Spacelabs monitor recorded a 10.2-mm Hg higher systolic pressure in the nonrandomized (P=.0016) and a 7.9-mm Hg higher systolic pressure in the randomized studies (P=.00008) compared with the Mobil-O-Graph. The mean arterial pressures were 1 mm Hg to 2 mm Hg different between monitors in the two studies, and heart rates were nearly identical. Our observations, if confirmed in larger cohorts, support the concern that ABPM device manufacturers consider developing normative databases for their devices. ©2013 Wiley Periodicals, Inc.

A multidisciplinary therapeutic approach for reducing the risk of psychiatric side effects in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin.

PubMed

Neri, Sergio; Bertino, Gaetano; Petralia, Antonio; Giancarlo, Crisafulli; Rizzotto, Agostino; Calvagno, Giuseppe Stefano; Mauceri, Barbara; Abate, Giuseppe; Boemi, Patrizia; Di Pino, Antonino; Ignaccolo, Luca; Vadalà, Giuseppe; Misseri, Maria; Maiorca, Daniela; Mastrosimone, Gianluca; Judica, Antonino; Palermo, Filippo

2010-10-01

To evaluate the effectiveness of psychiatric counseling in reducing the rate of development of psychiatric side effects of antiviral therapy with interferon-α and ribavirin among study participants compared with standard clinical monitoring alone. Interferon-α is used to treat chronic hepatitis C. Interferons may induce adverse events that usually, but not always, reverse within a few days after the end of therapy. Two hundred eleven patients with chronic hepatitis C, genotype 1b were treated with peginterferon and ribavirin for 48 weeks in a prospective trial. Two groups were randomly created. Group A was interviewed by a team of gastroenterologists, psychiatrists, and psychologists and treated with psychotherapy once a month. Group B was monitored once a month according to a conventional protocol that did not include psychotherapy. SVR (sustained viral response), severe psychiatric symptom onset, and mood progression were assessed (P calculated using Fisher exact test, Friedman test, Dunn posttest, and Mann-Whitney U-test). At baseline, there was no difference in depressive symptoms or liver histologic score between the 2 groups. The onset rate of severe psychiatric manifestations was 4.7% (Group A) and 16.1% (Group B) between the 24th and 36th weeks (P<0.01). Fifteen participants in Group A and 39 in Group B required antidepressants and benzodiazepines (P<0.05). Patients can develop depressive symptoms during interferon therapy. Multidisciplinary medical treatment with psychiatric counseling provided during the treatment of chronic hepatitis C may contribute to the decrease or prevent the higher rates of depression associated with interferon treatment.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

PubMed

Mukherjee, Partha S; Vishnubhatla, Sreenivas; Amarapurkar, Deepak N; Das, Kausik; Sood, Ajit; Chawla, Yogesh K; Eapen, Chundamannil E; Boddu, Prabhakar; Thomas, Varghese; Varshney, Subodh; Hidangmayum, Diamond Sharma; Bhaumik, Pradip; Thakur, Bhaskar; Acharya, Subrat K; Chowdhury, Abhijit

2017-01-01

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

The Hepatitis Testing and Linkage-to-Care Data Review Process: An Approach to Ensuring the Quality of Program Data.

PubMed

Mezzo, Jennifer L; Lamia, Tamara L; Danelski, Lisa L; Schipani, Anne Marie; Stokes, Scott A; Jacobs-Ware, Elizabeth D

2016-01-01

CDC's 2012 Hepatitis Testing and Linkage to Care (HepTLC) initiative was a nationally coordinated effort to conduct hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites. This project provided support for data management and monthly data reviews between awardees and a data manager, which facilitated monitoring of awardee progress and regular program improvement opportunities. CDC provided technical assistance to awardees for testing processes and program improvement, including Internet-based data submission, reporting software and data management to awardees, offering assistance with submitting, and reviewing data in real time. We describe how one awardee, AIDS Resource Center of Wisconsin (ARCW), used the data management process to improve data quality, inform testing processes and implementation, and measure and report missing variables from an online database. From October 2012 through July 2014, ARCW performed 2,255 HCV antibody (anti-HCV) tests and 244 HCV ribonucleic acid (RNA) tests as part of the HepTLC initiative. Participants who tested HCV RNA positive (n=189) were referred to medical care. At the end of the study, no records were missing for the anti-HCV test result or HCV RNA test result variables, and only one record was missing for those who were referred to medical care. Regular data review and monitoring by awardees and CDC-supported data managers provided opportunities for data quality and program improvement. Through regular data review, ARCW reduced the amount of missing data and promoted timely follow-up with participants testing positive for HCV to ensure receipt of results and linkage to care. Other programs can adopt a similar data management model.

Quantitative farm-to-fork risk assessment model for norovirus and hepatitis A virus in European leafy green vegetable and berry fruit supply chains.

PubMed

Bouwknegt, Martijn; Verhaelen, Katharina; Rzeżutka, Artur; Kozyra, Iwona; Maunula, Leena; von Bonsdorff, Carl-Henrik; Vantarakis, Apostolos; Kokkinos, Petros; Petrovic, Tamas; Lazic, Sava; Pavlik, Ivo; Vasickova, Petra; Willems, Kris A; Havelaar, Arie H; Rutjes, Saskia A; de Roda Husman, Ana Maria

2015-04-02

Fresh produce that is contaminated with viruses may lead to infection and viral gastroenteritis or hepatitis when consumed raw. It is thus important to reduce virus numbers on these foods. Prevention of virus contamination in fresh produce production and processing may be more effective than treatment, as sufficient virus removal or inactivation by post-harvest treatment requires high doses that may adversely affect food quality. To date knowledge of the contribution of various potential contamination routes is lacking. A risk assessment model was developed for human norovirus, hepatitis A virus and human adenovirus in raspberry and salad vegetable supply chains to quantify contributions of potential contamination sources to the contamination of produce at retail. These models were used to estimate public health risks. Model parameterization was based on monitoring data from European supply chains and literature data. No human pathogenic viruses were found in the soft fruit supply chains; human adenovirus (hAdV) was detected, which was additionally monitored as an indicator of fecal pollution to assess the contribution of potential contamination points. Estimated risks per serving of lettuce based on the models were 3×10(-4) (6×10(-6)-5×10(-3)) for NoV infection and 3×10(-8) (7×10(-10)-3×10(-6)) for hepatitis A jaundice. The contribution to virus contamination of hand-contact was larger as compared with the contribution of irrigation, the conveyor belt or the water used for produce rinsing. In conclusion, viral contamination in the lettuce and soft fruit supply chains occurred and estimated health risks were generally low. Nevertheless, the 97.5% upper limit for the estimated NoV contamination of lettuce suggested that infection risks up to 50% per serving might occur. Our study suggests that attention to full compliance for hand hygiene will improve fresh produce safety related to virus risks most as compared to the other examined sources, given the monitoring results. This effect will be further aided by compliance with other hygiene and water quality regulations in production and processing facilities. Copyright © 2015 Elsevier B.V. All rights reserved.

Tissue heavy metal concentrations of stranded California sea lions (Zalophus californianus) in Southern California.

PubMed

Harper, Erin R; St Leger, Judy A; Westberg, Jody A; Mazzaro, Lisa; Schmitt, Todd; Reidarson, Tom H; Tucker, Melinda; Cross, Dee H; Puschner, Birgit

2007-06-01

Concentrations of nine heavy metals (As, Cd, Cu, Fe, Hg, Pb, Mn, Mo and Zn) were determined in the hepatic and renal tissues of 80 stranded California sea lions (Zalophus californianus). Significant age-dependant increases were observed in liver and kidney concentrations of cadmium and mercury, and renal zinc concentrations. Hepatic iron concentrations were significantly higher in females than males. Animals with suspected domoic acid associated pathological findings had significantly higher concentrations of liver and kidney cadmium; and significantly higher liver mercury concentrations when compared to animals classified with infectious disease or traumatic mortality. Significantly higher hepatic burdens of molybdenum and zinc were found in animals that died from infectious diseases. This is the largest study of tissue heavy metal concentrations in California sea lions to date. These data demonstrate how passive monitoring of stranded animals can provide insight into environmental impacts on marine mammals.

The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

PubMed

Liu, Zhanyu

2017-09-01

By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

The HepHIV 2017 Conference in Malta: joining forces for the earlier diagnosis of HIV and viral hepatitis.

PubMed

Raben, D; Hoekstra, M; Sperle, I; Amato Gauci, A J; Gauci, C; West, B; Sullivan, A; Lazarus, J V; Platteau, T; Rockstroh, J K

2018-02-01

The objective of the article is to provide an overview of the results of the HepHIV 2017 Conference organized by the HIV in Europe initiative under the Maltese EU Presidency in January 2017. A thourough review of all conference presentations (oral and poster presentations) was performed to retrieve the key outcomes of the conference. The key result from the conference was a call to action summarising key priorities in HIV and viral hepatitis testing and linkage to care. This included improving monitoring of viral hepatitis and HIV, mixing testing strategies and ensuring policy support. The important contribution and outcomes of EU funded projects OptTEST and EuroHIVEdat was highlighted. An integrated approach to earlier testing and linkage to care across diseases is needed in Europe and the HepHIV conferences create an important forum to reach this aim. © 2018 British HIV Association.

[Effect of low-intensity laser radiation on the function of vascular endothelium in patients with chronic viral hepatitis].

PubMed

Burduli, N M; Krifaridi, A S

2009-01-01

The aim of the study was to measure plasma levels of stable metabolites of nitric oxide, nitrates, and nitrites (NOx) in patients with chronic viral hepatitis and evaluate the possibility of their correction by low-power laser irradiation. NO metabolites (total nitrites and nitrates) were measured colorimetrically from the development of colour in the reaction of nitrite with sulfanilamide diazotization in Griess reagent. Colour intensity was determined with Victor2 enzyme immunoanalyzer, Perkin Elmaer (Finland). The patients were divided into three groups. In group 1 (control, n = 30) they received combined medicamentous therapy, in group 2 (n = 45) medicamentous therapy and a course of intravenous laser therapy, in goup 3 (n = 45) medicamentous therapy and skin laserotherapy. The results indicate that medicamentous treatment of patients with chronic hepatitis does not bring any beneficial changes in plasma NOx whose levels are significantly improved in case of simultaneous laser therapy. It is concluded that different laserotherapeutic modalities have beneficial effect on NO-producing function of endothelium and thereby improve its functional state. Compensation of NO deficit by laser therapy ensures overall protection of the organism against free radicals and decreases severity of oxidative stress.

Vitamin E and selenium interrelations in the diet of Atlantic salmon (Salmo salar): Gross, histological and biochemical deficiency signs

USGS Publications Warehouse

Poston, Hugh A.; Combs, G.F.; Leibovitz, Louis

1976-01-01

Either simultaneous or separate dietary deficiencies of vitamin E and selenium in Atlantic salmon during first 4 weeks of feeding caused twice the mortality shown in fish fed both supplemental vitamin E (0.5 IU/g dry diet) and selenium (0.1 µg/g). Subsequent dietary repletion with both vitamin E and selenium significantly reduced mortality during the following 2 weeks. Larger salmon (0.9 g initial mean weight), with vitamin E deficiency with or without selenium resulted in the following deficiency signs: extreme anemia, pale gills, anisocytosis, poikilocytosis, elevated plasma protein, exudative diathesis, dermal depigmentation, in vitro ascorbic acid-stimulated peroxidation in hepatic microsomes, yellow-orange liver color, yellow-brown intestinal contents, enlarged gall bladder distended with dark green bile, low vitamin E in carcass and hepatic tissue, muscular dystrophy, increased carcass fat and water, and a response to handling characterized by a transitory fainting with interruption in swimming. A deficiency of dietary selenium suppressed plasma glutathione peroxidase activity. Supplemental selenium with vitamin E significantly increased tocopherol activity in hepatic, but not carcass tissues. Supplements of both vitamin E and selenium were necessary to prevent muscular dystrophy.

Pre-set extrusion bioprinting for multiscale heterogeneous tissue structure fabrication.

PubMed

Kang, Donggu; Ahn, Geunseon; Kim, Donghwan; Kang, Hyun-Wook; Yun, Seokhwan; Yun, Won-Soo; Shim, Jin-Hyung; Jin, Songwan

2018-06-06

Recent advances in three-dimensional bioprinting technology have led to various attempts in fabricating human tissue-like structures. However, current bioprinting technologies have limitations for creating native tissue-like structures. To resolve these issues, we developed a new pre-set extrusion bioprinting technique that can create heterogeneous, multicellular, and multimaterial structures simultaneously. The key to this ability lies in the use of a precursor cartridge that can stably preserve a multimaterial with a pre-defined configuration that can be simply embedded in a syringe-based printer head. The multimaterial can be printed and miniaturized through a micro-nozzle without conspicuous deformation according to the pre-defined configuration of the precursor cartridge. Using this system, we fabricated heterogeneous tissue-like structures such as spinal cords, hepatic lobule, blood vessels, and capillaries. We further obtained a heterogeneous patterned model that embeds HepG2 cells with endothelial cells in a hepatic lobule-like structure. In comparison with homogeneous and heterogeneous cell printing, the heterogeneous patterned model showed a well-organized hepatic lobule structure and higher enzyme activity of CYP3A4. Therefore, this pre-set extrusion bioprinting method could be widely used in the fabrication of a variety of artificial and functional tissues or organs.

The Oral Minimal Model Method

PubMed Central

Cobelli, Claudio; Dalla Man, Chiara; Toffolo, Gianna; Basu, Rita; Vella, Adrian; Rizza, Robert

2014-01-01

The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism. PMID:24651807

Kinetic sensitivity of a receptor-binding radiopharmaceutical: Technetium-99m galactosyl-neoglycoalbumin

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

Vera, D.R.; Woodle, E.S.; Stadalnik, R.C.

1989-09-01

Kinetic sensitivity is the ability of a physiochemical parameter to alter the time-activity curve of a radiotracer. The kinetic sensitivity of liver and blood time-activity data resulting from a single bolus injection of ({sup 99m}Tc)galactosyl-neoglycoalbumin (( Tc)NGA) into healthy pigs was examined. Three parameters, hepatic plasma flow scaled as flow per plasma volume, ligand-receptor affinity, and total receptor concentration, were tested using (Tc)NGA injections of various molar doses and affinities. Simultaneous measurements of plasma volume (iodine-125 human serum albumin dilution), and hepatic plasma flow (indocyanine green extraction) were performed during 12 (Tc)NGA studies. Paired data sets demonstrated differences (P(chi v2)more » less than 0.01) in liver and blood time-activity curves in response to changes in each of the tested parameters. We conclude that the (Tc)NGA radiopharmacokinetic system is therefore sensitive to hepatic plasma flow, ligand-receptor affinity, and receptor concentration. In vivo demonstration of kinetic sensitivity permits delineation of the physiologic parameters that determine the biodistribution of a radiopharmaceutical. This delineation is a prerequisite to a valid analytic assessment of receptor biochemistry via kinetic modeling.« less

Determinants of [13N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model.

PubMed

Weiss, Michael; Roelsgaard, Klaus; Bender, Dirk; Keiding, Susanne

2002-12-01

The aim of this study was the development of a modelling approach for the analysis of the systemic kinetics of the tracer nitrogen-13 ammonia administered for dynamic liver scanning. The radioactive half-life of this tracer is 9.8 min, which limits the time span in which data are available in a positron emission tomography experimental setting. A circulatory pharmacokinetic model was applied to the metabolism of ammonia in anaesthetised pigs, which incorporated data from serial measurements of [(13)N]ammonia and [(13)N]metabolite activity in arterial and portal venous blood together with blood flow rates through the portal vein and through the hepatic artery obtained over 20 min after intravenous injection of [(13)N]ammonia. Model analysis showed that up to 20 min after injection the time course of [(13)N]ammonia concentration in arterial blood is primarily determined by distribution kinetics (steady-state volume of distribution 1,856+/-531 ml kg(-1)). Simultaneous fitting of arterial ammonia and metabolite blood concentrations allowed for estimation of the hepatic [(13)N]ammonia clearance (10.25+/-1.84 ml min(-1) kg(-1)), which accounted for the formation of the circulating metabolites.

Selective pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of internal anal sphincter and bladder innervation.

PubMed

Kneist, W; Kauff, D W; Koch, K P; Schmidtmann, I; Heimann, A; Hoffmann, K P; Lang, H

2011-01-01

Pelvic autonomic nerve preservation avoids postoperative functional disturbances. The aim of this feasibility study was to develop a neuromonitoring system with simultaneous intraoperative verification of internal anal sphincter (IAS) activity and intravesical pressure. 14 pigs underwent low anterior rectal resection. During intermittent bipolar electric stimulation of the inferior hypogastric plexus (IHP) and the pelvic splanchnic nerves (PSN), electromyographic signals of the IAS and manometry of the urinary bladder were observed simultaneously. Stimulation of IHP and PSN as well as simultaneous intraoperative monitoring could be realized with an adapted neuromonitoring device. Neurostimulation resulted in either bladder or IAS activation or concerted activation of both. Intravesical pressure increase as well as amplitude increase of the IAS neuromonitoring signal did not differ significantly between stimulation of IHP and PSN [6.0 cm H(2)O (interquartile range [IQR] 3.5-9.0) vs. 6.0 cm H(2)O (IQR 3.0-10.0) and 12.1 μV (IQR 3.0-36.7) vs. 40.1 μV (IQR 9.0-64.3)] (p > 0.05). Pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of IAS and bladder innervation is feasible. The method may enable neuromonitoring with increasing selectivity for pelvic autonomic nerve preservation. Copyright © 2011 S. Karger AG, Basel.

Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans.

PubMed

Gancheva, Sofiya; Koliaki, Chrysi; Bierwagen, Alessandra; Nowotny, Peter; Heni, Martin; Fritsche, Andreas; Häring, Hans-Ulrich; Szendroedi, Julia; Roden, Michael

2015-06-01

Studies in rodents suggest that insulin controls hepatic glucose metabolism through brain-liver crosstalk, but human studies using intranasal insulin to mimic central insulin delivery have provided conflicting results. In this randomized controlled crossover trial, we investigated the effects of intranasal insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance spectroscopy. Intranasal insulin transiently increased serum insulin levels followed by a gradual lowering of blood glucose in CON only. Fasting HIS index was not affected by intranasal insulin in CON and patients. HCLs decreased by 35% in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3 h. A subgroup of CON received intravenous insulin to mimic the changes in serum insulin and blood glucose levels observed after intranasal insulin. This resulted in a 34% increase in HCLs without altering hepatic ATP concentrations. In conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic energy metabolism in healthy humans, which is independent of peripheral insulinemia. These effects are blunted in patients with type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Simultaneous Detection of Flavonoids, Phenolic Acids and Alkaloids in Abri Herba and Abri Mollis Herba using Liquid Chromatography Tandem Mass Spectrometry.

PubMed

Yan, Wenying; Han, Qingjie; Guo, Panpan; Wang, Chunying; Zhang, Zijian

2016-01-01

Abri Herba has remarkable properties, such as cleanup heat detoxification, dampness and activating blood circulation to dissipate blood stasis; as a result, it has been applied to treat acute or chronic hepatitis and mastitis. Abri mollis Herba is often used as Abri Herba. Hierarchical cluster analysis (HCA) was applied to compare the similarities and differences of the chemical compositions in the two types of medicinal materials. To establish a high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous analysis of 15 flavonoids, two phenolic acids and three alkaloids in Abri Herba and Abri mollis Herba. The chromatographic separation was performed on a C18 column with a mobile phase of methanol (A), acetonitrile (B) and 0.5‰ acetic acid in water (C) using gradient elution. The detection of the target compounds was performed in multiple-reaction monitoring (MRM) mode using a hybrid quadrupole linear ion trap mass spectrometer equipped with positive/negative ion-switching electrospray ionisation (ESI) source. The developed method is reliable, sensitive and specific. In addition, the method has been successfully applied to differentiate 15 batches of Abri Herba and 27 batches of Abri mollis Herba stems. Furthermore, a comparison of the contents among stems, roots and leaves from the same strain in seven batches of Abri mollis Herba and four batches of Abri Herba has also been performed. HPLC-MS/MS method is sensitive and selective and can be suitable for the reliable quality control of Abri mollis Herba and Abri Herba. Copyright © 2015 John Wiley & Sons, Ltd.

Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation.

PubMed

Carrión, Jose A; Navasa, Miquel; Bosch, Jaume; Bruguera, Miquel; Gilabert, Rosa; Forns, Xavier

2006-12-01

Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow-up hepatitis C virus (HCV)-induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV-infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0-F1) in 96 cases (57%) and significant (F2-F4) in 73 (43%). HVPG was normal (<6 mm Hg) in 69 cases (54%) and elevated (>or=6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis >or=F2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis >or=F2, >or=F3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P < 0.001) and the AUC for diagnosis of portal hypertension (HVPG >or=6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG >or=10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow-up liver biopsies.

Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.

PubMed

Wang, Zhenli; Zhang, Zemin; Du, Ning; Wang, Kai; Li, Lei

2015-01-01

Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor β-1 (TGF-β1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-β (IL-1β), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-β1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4. GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.

Diagnostic value of the fluoroscopic triggering 3D LAVA technique for primary liver cancer.

PubMed

Shen, Xiao-Yong; Chai, Chun-Hua; Xiao, Wen-Bo; Wang, Qi-Dong

2010-04-01

Primary liver cancer (PLC) is one of the common malignant tumors. Liver acquisition with acceleration volume acquisition (LAVA), which allows simultaneous dynamic enhancement of the hepatic parenchyma and vasculature imaging, is of great help in the diagnosis of PLC. This study aimed to evaluate application of the fluoroscopic triggering 3D LAVA technique in the imaging of PLC and liver vasculature. The clinical data and imaging findings of 38 adults with PLC (22 men and 16 women; average age 52 years), pathologically confirmed by surgical resection or biopsy, were collected and analyzed. All magnetic resonance images were obtained with a 1.5-T system (General Electrics Medical Systems) with an eight-element body array coil and application of the fluoroscopic triggering 3D LAVA technique. Overall image quality was assessed on a 5-point scale by two experienced radiologists. All the nodules and blood vessel were recorded and compared. The diagnostic accuracy and feasibility of LAVA were evaluated. Thirty-eight patients gave high quality images of 72 nodules in the liver for diagnosis. The accuracy of LAVA was 97.2% (70/72), and the coincidence rate between the extent of tumor judged by dynamic enhancement and pathological examination was 87.5% (63/72). Displayed by the maximum intensity projection reconstruction, nearly all cases gave satisfactory images of branches III and IV of the hepatic artery. Furthermore, small early-stage enhancing hepatic lesions and the parallel portal vein were also well displayed. Sequence of LAVA provides good multi-phase dynamic enhancement scanning of hepatic lesions. Combined with conventional scanning technology, LAVA effectively and safely displays focal hepatic lesions and the relationship between tumor and normal tissues, especially blood vessels.

GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

PubMed Central

Wang, H; Cao, Y

2012-01-01

Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using CUDA-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, non-linear least squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626400 voxels in a patient’s liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10−6. The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645

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

PubMed Central

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

2015-01-01

Background 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. Methods 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. Results 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. Conclusions 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. PMID:26107467

Ginger extract modulates Pb-induced hepatic oxidative stress and expression of antioxidant gene transcripts in rat liver.

PubMed

Mohamed, Omnia Ismail; El-Nahas, Abeer Fekry; El-Sayed, Yasser Said; Ashry, Khaled Mohamed

2016-07-01

Spices and herbs are recognized sources of natural antioxidants that can protect from oxidative stress, thus play an important role in chemoprevention of liver diseases. Ginger is used worldwide primarily as a spicy condiment. This study evaluated the ability of ginger extract (GE) to ameliorate oxidative-hepatic toxicity induced by lead acetate (PbAc) in rats. Five groups of animals were used: group I kept as control; groups II, IV, and V received PbAc (1 ppm in drinking water daily for 6 weeks, and kept for an additional 2 weeks without PbAc exposure); group III treated orally with GE (350 mg/kg body weight, 4 d per week) for 6 weeks; group IV (protective) received GE for 2 weeks before and simultaneously with PbAc; and group V (treatment) received GE for 2 weeks after PbAc exposure. GC-MS analysis of GE revealed its content of gingerol (7.09%), quercetin (3.20%), dl-limonene (0.96%), and zingiberene (0.18%). Treatment of PbAc-treated rats with GE has no effect on hepatic Pb concentrations. However, it maintained serum aspartate aminotransferase level, increased hepatic glutathione (157%), glutathione S-transferase (GST) (228%), glutathione peroxidase (GPx) (138%) and catalase (CAT) (112%) levels, and reduced hepatic malondialdehyde (80%). Co-treatment of PbAc group with GE upregulated mRNA expression of antioxidant genes: GST-α1 (1.4-fold), GPx1 (1.8-fold), and CAT (8-fold), while post-treatment with GE upregulated only mRNA expression of GPx1 (1.5-fold). GE has an antioxidant protective efficacy against PbAc-induced hepatotoxicity, which appears more effective than its therapeutic application. However, the changes in antioxidant gene expression were not reflected at the protein level.

Simultaneous Time, Wavelength and Intensity Measurement of Optical Memory Subsystems

DTIC Science & Technology

1998-07-01

SIMULTANEOUS TIME, WAVELENGTH AND INTENSITY MEASUREMENT PE - 61102F OF OPTICAL MEMORY SUBSYSTEMS PR - 2300 6. AUTHOR( S ) TA - 06 WU -03 Joseph Osman and...Rebecca Bussjager 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER AFRL/SNDP25 letnic AFRL-SN-RS-TR- 1998...12025 Electronic Pky Rome, NY 13441-4515 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSORING/MONITORING AGENCY REPORT NUMBER

Simultaneous laser-induced fluorescence and scattering detection of individual particles separated by capillary electrophoresis.

PubMed

Andreyev, Dmitry; Arriaga, Edgar A

2007-07-15

This technical note describes a detector capable of simultaneously monitoring scattering and fluorescence signals of individual particles separated by capillary electrophoresis. Due to its nonselective nature, scattering alone is not sufficient to identify analyte particles. However, when the analyte particles are fluorescent, the detector described here is able to identify simultaneously occurring scattering and fluorescent signals, even when contaminating particles (i.e., nonfluorescent) are present. Both fluorescent polystyrene particles and 10-nonyl acridine orange (NAO)-labeled mitochondria were used as models. Fluorescence versus scattering (FVS) plots made it possible to identify two types of particles and a contaminant in a mixture of polystyrene particles. We also analyzed NAO-labeled mitochondria before and after cryogenic storage; the mitochondria FVS plots changed with storage, which suggests that the detector reported here is suitable for monitoring subtle changes in mitochondrial morphology that would not be revealed by monitoring only fluorescence or scattering signals.

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device.

PubMed

Cordeiro, C A; de Vries, M G; Ngabi, W; Oomen, P E; Cremers, T I F H; Westerink, B H C

2015-05-15

Enzyme-based amperometric biosensors are widely used for monitoring key biomarkers. In experimental neuroscience there is a growing interest in in vivo continuous and simultaneous monitoring of metabolism-related biomarkers, like glucose, lactate and pyruvate. The use of multiplex biosensors will provide better understanding of brain energy metabolism and its role in neuropathologies such as diabetes, ischemia, and epilepsy. We have developed and characterized an implantable multiplex microbiosensor device (MBD) for simultaneous and continuous in vivo monitoring of glucose, lactate, and pyruvate. First, we developed and characterized amperometric microbiosensors for monitoring lactate and pyruvate. In vitro evaluation allowed us to choose the most suitable biosensors for incorporation into the MBD, along with glucose and background biosensors. Fully assembled MBDs were characterized in vitro. The calculated performance parameters (LOD, LR, LRS, IMAX and appKM) showed that the multiplex MBD was highly selective and sensitive (LRS≥100 nA/mM) for each analyte and within an adequate range for in vivo application. Finally, MBDs were implanted in the mPFC of anesthetized adult male Wistar rats for in vivo evaluation. Following an equilibration period, baseline brain levels of glucose (1.3±0.2 mM), lactate (1.5±0.4 mM) and pyruvate (0.3±0.1 mM) were established. Subsequently, the MBDs recorded the responses of the animals when submitted to hyperglycemic (40% glucose i.v.) and hypoglycemic (5 U/kg insulin i.v.) challenges. Afterwards, MBDs were recalibrated to convert electrochemical readings into accurate substrate concentrations and to assess biofouling. The presented MBD can monitor simultaneously multiple biomarkers in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Aspergillus vertebral osteomyelitis and ureteral obstruction after liver transplantation.

PubMed

Zhu, L-P; Chen, X-S; Wu, J-Q; Yang, F-F; Weng, X-H

2011-04-01

Aspergillus osteomyelitis has been reported as a result of dissemination in solid organ transplant recipients. Vertebral osteomyelitis is one of the most common forms of Aspergillus osteomyelitis. An Aspergillus fungal ball is a rare cause of ureteral obstruction. We describe an unusual case of simultaneous vertebral osteomyelitis and ureteral obstruction caused by A. flavus in a hepatic transplant recipient, who was successfully treated with sequential intravenous and oral itraconazole solution. © 2011 John Wiley & Sons A/S.

Ambulatory monitoring of activities and motor symptoms in Parkinson's disease.

PubMed

Zwartjes, Daphne G M; Heida, Tjitske; van Vugt, Jeroen P P; Geelen, Jan A G; Veltink, Peter H

2010-11-01

Ambulatory monitoring of motor symptoms in Parkinsons disease (PD) can improve our therapeutic strategies, especially in patients with motor fluctuations. Previously published monitors usually assess only one or a few basic aspects of the cardinal motor symptoms in a laboratory setting. We developed a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing current motor activity of the patient (e.g. sitting, walking) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia. The monitor consists of a set of four inertial sensors. Validity of our monitor was established in seven healthy controls and six PD patients treated with deep brain stimulation (DBS) of the subthalamic nucleus. Patients were tested at three different levels of DBS treatment. Subjects were monitored while performing different tasks, including motor tests of the Unified Parkinsons Disease Rating Scale (UPDRS). Output of the monitor was compared to simultaneously recorded videos. The monitor proved very accurate in discriminating between several motor activities. Monitor output correlated well with blinded UPDRS ratings during different DBS levels. The combined analysis of motor activity and symptom severity by our PD monitor brings true ambulatory monitoring of a wide variety of motor symptoms one step closer..

Fibrin glue as a hemostatic agent in hepatic and splenic trauma.

PubMed

Ochsner, M G; Maniscalco-Theberge, M E; Champion, H R

1990-07-01

Fibrin glue is a biologic hemostatic agent that coagulates and seals upon application. It is made by combining human fibrinogen concentrate with standard thrombin solutions containing calcium. Similar to epoxy glue, the two components are applied simultaneously in equal volumes resulting in an almost instantaneous formation of a coagulum. Fibrinogen concentrate is prepared in the blood bank from single donor plasma. Fibrin glue can be applied topically or injected into the parenchyma of solid organs. Twenty-six patients sustained hepatic or splenic trauma from May through August 1989--17 liver and nine splenic injuries. The glue was effective after one application in 21 patients and after a second in five. Hemostasis was achieved despite coagulopathy and thrombocytopenia in eight patients. There were no re-explorations for bleeding, and nine complications occurred in six patients. Our experience suggests fibrin glue is an effective, underutilized adjunctive hemostatic agent in trauma.

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

Hsia, Chu Chieh; Chizhikov, Vladimir E.; Yang, Amy X.

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type-1 (HIV-1) are transfusion-transmitted human pathogens that have a major impact on blood safety and public health worldwide. We developed a microarray multiplex assay for the simultaneous detection and discrimination of these three viruses. The microarray consists of 16 oligonucleotide probes, immobilized on a silylated glass slide. Amplicons from multiplex PCR were labeled with Cy-5 and hybridized to the microarray. The assay detected 1 International Unit (IU), 10 IU, 20 IU of HBV, HCV, and HIV-1, respectively, in a single multiplex reaction. The assay also detected and discriminatedmore » the presence of two or three of these viruses in a single sample. Our data represent a proof-of-concept for the possible use of highly sensitive multiplex microarray assay to screen and confirm the presence of these viruses in blood donors and patients.« less

42 CFR 494.30 - Condition: Infection control.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (with the exception of screening for hepatitis C), found in “Recommendations for Preventing Transmission of Infections Among Chronic Hemodialysis Patients,” developed by the Centers for Disease Control and... Patient Safety § 494.30 Condition: Infection control. The dialysis facility must provide and monitor a...

Research in Review. Child Care and Disease: What Is the Link?

ERIC Educational Resources Information Center

Kendall, Earline D.

1983-01-01

Briefly reviews current research in the United States on hepatitis, some diarrheal diseases, and infections caused by H-flu, suggesting that group care (especially when not carefully monitored) presents risks for very young children, care providers, families, and the community. (RH)

[Indirect ELISA for simultaneous detection of antibodies against duck hepatitis A type 1 and 3 viruses].

PubMed

Zhang, Yuyao; Ma, Xiuli; Huang, Bing; Li, Yufeng; Yu, Kexiang; Li, Jianliang; Liu, Cunxia; Han, Hongyu; Cui, Yanshun

2015-04-04

To simultaneously detect antibodies against Duck hepatitis A type 1 (DHAV-1) and type 3 (DHAV-3) viruses, we developed an indirect enzyme-linked immunosobent assay (ELISA) with bacterially expressed recombinant viral protein as antigen in Escherichia coli. We amplified the full-length VP3 gene of DHAV-1 and the full-length VP1 gene of DHAV-3 through reverse transcription-polymerase chain reaction (RT-PCR) and then cloned them into pET-32a expression vector, designated as pET-1VP3-3VP1. The fusion protein DHAV-1VP3-3VP1 expressed correctly and was subsequently used to develop an indirect ELISA assay. DHAV-1VP3-3VP1 fusion protein expressed in BL21 (DE3) cells following induction by Isopropyl-beta-D-1-thiogalactopyranoside (IPTG). The expressed protein was very antigenic and reactive to virus-specific antibodies in western blot assay. The optimal working concentration for coating antigen was 1.0 microg per well and the working concentration of serum samples was 1:200 dilution and the cut-off value that distinguished the positive from negative serum samples was OD650 > OR = 0.38. The ELISA method based on the prokaryotic expression of VP3 (DHAV-1) and VP1 proteins (DHAV-3) can be used effectively for the clinical detection antibodies against DHAV-1 and DHAV-3.

[Sterilization effect analysis of B-class pulsation table top vacuum sterilizer to dental handpieces].

PubMed

Zeng, Shu-Rong; Jiang, Bo; Xiao, Xiao-Rong

2007-06-01

Discuss sterilization effect of B-class pulsation table top vacuum pressure steam sterilizer for dental handpiece. Analysis selection of sterilizer for dental handpiece and sterilization management processes and sterilization effect monitoring, evaluation of monitoring result and effective sterilization method. The B-class pulsation table top vacuum pressure steam sterilizer to dental handpiece in West China Stomatological Hospital of Sichuan University met the requirement of the chemical and biological monitoring. Its efficiency of sterilization was 100%. The results of aerobic culture, anaerobic culture, B-type hepatitis mark monitoring to sterilized dental handpiece were negative. It is effective method for dental handpiece sterilization to use B-class pulsation table top vacuum pressure steam sterilizer.

Chemosaturation with Percutaneous Hepatic Perfusion for Unresectable Isolated Hepatic Metastases from Sarcoma

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

Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org; Choi, Junsung; Gonzalez, Ricardo J.

Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significantmore » improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.« less

A risk-adjusted O-E CUSUM with monitoring bands for monitoring medical outcomes.

PubMed

Sun, Rena Jie; Kalbfleisch, John D

2013-03-01

In order to monitor a medical center's survival outcomes using simple plots, we introduce a risk-adjusted Observed-Expected (O-E) Cumulative SUM (CUSUM) along with monitoring bands as decision criterion.The proposed monitoring bands can be used in place of a more traditional but complicated V-shaped mask or the simultaneous use of two one-sided CUSUMs. The resulting plot is designed to simultaneously monitor for failure time outcomes that are "worse than expected" or "better than expected." The slopes of the O-E CUSUM provide direct estimates of the relative risk (as compared to a standard or expected failure rate) for the data being monitored. Appropriate rejection regions are obtained by controlling the false alarm rate (type I error) over a period of given length. Simulation studies are conducted to illustrate the performance of the proposed method. A case study is carried out for 58 liver transplant centers. The use of CUSUM methods for quality improvement is stressed. Copyright © 2013, The International Biometric Society.

Exposure to heat and freezing in the vaccine cold chain in Thailand.

PubMed

Techathawat, Sirirat; Varinsathien, Porpit; Rasdjarmrearnsook, Aimorn; Tharmaphornpilas, Piyanit

2007-01-26

This study investigated exposure to heat and freezing of vaccines used in Thailand's National Immunization Program. Cold chain temperatures on 48 randomly selected shipment routes nationwide were monitored. Measles and hepatitis B vaccines were despatched with recording devices and subsequently tested. The study found that extremes of cold appear to be the more significant problem. Heat exposure was relatively brief and not at very high temperatures, so vaccine deterioration was unlikely, as was confirmed by measles vaccine testing. Exposure to temperatures below -0.5 degrees C was widespread, which would be expected to damage hepatitis B vaccine, but shake tests did not detect damage.

Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

PubMed Central

Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

2012-01-01

A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

Effects of atrazine on hepatic metabolism and endocrine homeostasis in rainbow trout (Oncorhynchus mykiss)

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

Salaberria, Iurgi; Department of Biology, Norwegian University of Science and Technology, N-7491 Trondheim; Hansen, Bjorn Henrik

2009-01-01

The herbicide atrazine (ATZ) is one of the most widely used pesticides in the world and is now under scrutiny for its alleged capacity to disrupt the endocrine system. Exhibiting negligible interaction with the estrogen receptor (ER), ATZ's mode of action remains to be elucidated. ATZ may act as an inducer of the enzyme aromatase, which converts androgens to estrogens, although other mechanisms should also be taken into consideration such as impairment of hepatic metabolism. Therefore we administered juvenile rainbow trout (Oncorhynchus mykiss) a dose of either 2 or 200 {mu}g ATZ/kg, or of carrier control phosphate buffered saline (PBS)more » and we measured plasma concentrations of testosterone (T), 17beta-estradiol (E2) and vitellogenin (Vtg) 6 days after exposure. Simultaneously we analyzed hepatic gene expression of cytochrome P450 (CYP) 1A and pi-class glutathione S-transferase (GST-P), and catalase (CAT) activity. Although sex steroid levels showed no significant alterations, we found a dose-dependent increase in Vtg and a concomitant decrease in CYP1A. There was no effect of ATZ on GST-P mRNA levels but GST-P was positively correlated with CYP1A. Also, CYP1A was negatively correlated with liver CAT and E2, and varied with T concentrations in a hormetic manner. The results showed that ATZ can alter hepatic metabolism, induce estrogenic effects and oxidative stress in vivo, and that these effects are linked.« less

Multipolar hepatic radiofrequency ablation using up to six applicators: preliminary results.

PubMed

Bruners, P; Schmitz-Rode, T; Günther, R W; Mahnken, A

2008-03-01

To evaluate the clinical feasibility and safety of hepatic radiofrequency (RF) ablation using a multipolar RF system permitting the simultaneous use of up to six electrodes. Ten patients (3 female, 7 male, mean age 61) suffering from 29 hepatic metastases (range: 1 - 5) of different tumors were treated with a modified multipolar RF system (CelonLab Power, Celon Medical Instruments, Teltow, Germany) operating four to six needle-shaped internally cooled RF applicators. The procedure duration, applied energy and generator output were recorded during the intervention. The treatment result and procedure-related complications were analyzed. The achieved coagulation volume was calculated on the basis of contrast-enhanced CT scans 24 hours after RF ablation. Complete tumor ablation was achieved in all cases as determined by the post-interventional lack of contrast enhancement in the target region using four applicators in five patients, five applicators in one patient and six applicators in four patients. A mean energy deposition of 353.9 +/- 176.2 kJ resulted in a mean coagulation volume of 115.9 +/- 79.5 cm (3). The mean procedure duration was 74.9 +/- 21.2 minutes. Four patients showed an intraabdominal hemorrhage which necessitated further interventional treatment (embolization; percutaneous histoacryl injection) in two patients. Multipolar RF ablation of hepatic metastasis with up to six applicators was clinically feasible. In our patient population it was associated with an increased risk of intraabdominal bleeding probably due to the multiple punctures associated with the use of multiple applicators.

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

PubMed

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors.

PubMed

Elaidy, Samah M; Hussain, Mona A; El-Kherbetawy, Mohamed K

2018-05-01

Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg -1 ·day -1 ) or NTZ (200 mg·kg -1 ·day -1 ) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

Simultaneous stimulated Raman scattering and higher harmonic generation imaging for liver disease diagnosis without labeling

NASA Astrophysics Data System (ADS)

Lin, Jian; Wang, Zi; Zheng, Wei; Huang, Zhiwei

2014-02-01

Nonlinear optical microscopy (e.g., higher harmonic (second-/third- harmonic) generation (HHG), simulated Raman scattering (SRS)) has high diagnostic sensitivity and chemical specificity, making it a promising tool for label-free tissue and cell imaging. In this work, we report a development of a simultaneous SRS and HHG imaging technique for characterization of liver disease in a bile-duct-ligation rat-modal. HHG visualizes collagens formation and reveals the cell morphologic changes associated with liver fibrosis; whereas SRS identifies the distributions of hepatic fat cells formed in steatosis liver tissue. This work shows that the co-registration of SRS and HHG images can be an effective means for label-free diagnosis and characterization of liver steatosis/fibrosis at the cellular and molecular levels.

USE OF CITIZEN BIRD POPULATION MONITORING DATA FOR ECOLOGICAL RISK ASSESSMENT

EPA Science Inventory

Birds are among the most conspicuous and easily monitored indicators of environmental health and change. Although volunteer avian monitoring ('citizen science') programs provide unique opportunities to gather data at fine and broad geographic scales simultaneously, and over long...

Chirped fiber Bragg grating written in highly birefringent fiber in simultaneous strain and temperature monitoring.

PubMed

Bieda, Marcin S; Sobotka, Piotr; Woliński, Tomasz R

2017-02-20

A new sensor configuration is proposed for simultaneous strain and temperature monitoring in a composite material that is based on a chirped fiber Bragg grating (CFBG) written in a highly birefringent (HB) polarization-maintaining fiber. The sensor is designed in the reflective configuration in which the CFBG acts both as a reflector and a sensing element. Since CFBG and HB fiber induce changes in the state of polarization (SOP), interference between polarization modes in the reflected spectrum is observed and analyzed. We used a simple readout setup to enable fast, linear operation of strain sensing as well simultaneous strain and temperature measurements in the composite.

Optimal Design of Multitype Groundwater Monitoring Networks Using Easily Accessible Tools.

PubMed

Wöhling, Thomas; Geiges, Andreas; Nowak, Wolfgang

2016-11-01

Monitoring networks are expensive to establish and to maintain. In this paper, we extend an existing data-worth estimation method from the suite of PEST utilities with a global optimization method for optimal sensor placement (called optimal design) in groundwater monitoring networks. Design optimization can include multiple simultaneous sensor locations and multiple sensor types. Both location and sensor type are treated simultaneously as decision variables. Our method combines linear uncertainty quantification and a modified genetic algorithm for discrete multilocation, multitype search. The efficiency of the global optimization is enhanced by an archive of past samples and parallel computing. We demonstrate our methodology for a groundwater monitoring network at the Steinlach experimental site, south-western Germany, which has been established to monitor river-groundwater exchange processes. The target of optimization is the best possible exploration for minimum variance in predicting the mean travel time of the hyporheic exchange. Our results demonstrate that the information gain of monitoring network designs can be explored efficiently and with easily accessible tools prior to taking new field measurements or installing additional measurement points. The proposed methods proved to be efficient and can be applied for model-based optimal design of any type of monitoring network in approximately linear systems. Our key contributions are (1) the use of easy-to-implement tools for an otherwise complex task and (2) yet to consider data-worth interdependencies in simultaneous optimization of multiple sensor locations and sensor types. © 2016, National Ground Water Association.

2006 Pathogen and Toxin Concentration Systems for Water Monitoring

DTIC Science & Technology

2012-07-24

design and construct a compact, portable automated device enabling the simultaneous concentration of protozoa , bacteria, bacterial spores, algae and...portable automated device enabling the simultaneous concentration of protozoa , bacteria, bacterial spores, algae and viruses from large volumes of various...construct a compact, portable automated device enabling the simultaneous concentration of protozoa , bacteria, bacterial spores, algae and viruses

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

PubMed Central

Kuo, I fan; Ensom, Mary H H

2009-01-01

Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective: To determine the utility of therapeutic drug monitoring for voriconazole. Methods: A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole. Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug–drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug–drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25–2 mg/L and 4–6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions: Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility. PMID:22478935

Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β.

PubMed

Santos, Juliana Célia F; de Araújo, Orlando R P; Valentim, Iara B; de Andrade, Kívia Queiroz; Moura, Fabiana Andréa; Smaniotto, Salete; dos Santos, John Marques; Gasparotto, Juciano; Gelain, Daniel P; Goulart, Marília O F

2015-01-01

This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1β. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1β, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.

Integrated photovoltaic (PV) monitoring system

NASA Astrophysics Data System (ADS)

Mahinder Singh, Balbir Singh; Husain, NurSyahidah; Mohamed, Norani Muti

2012-09-01

The main aim of this research work is to design an accurate and reliable monitoring system to be integrated with solar electricity generating system. The performance monitoring system is required to ensure that the PVEGS is operating at an optimum level. The PV monitoring system is able to measure all the important parameters that determine an optimum performance. The measured values are recorded continuously, as the data acquisition system is connected to a computer, and data is stored at fixed intervals. The data can be locally used and can also be transmitted via internet. The data that appears directly on the local monitoring system is displayed via graphical user interface that was created by using Visual basic and Apache software was used for data transmission The accuracy and reliability of the developed monitoring system was tested against the data that captured simultaneously by using a standard power quality analyzer device. The high correlation which is 97% values indicates the level of accuracy of the monitoring system. The aim of leveraging on a system for continuous monitoring system is achieved, both locally, and can be viewed simultaneously at a remote system.

Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B.

PubMed

Lin, Jueying; Zhuo, Yufeng; Zhang, Dongdong

2017-08-29

An increasing number of case reports suggest that acquired renal Fanconi syndrome may be associated with prolonged use of adefovir against hepatitis B virus. Renal Fanconi syndrome is an uncommon disease, and its complication with nephrolithiasis is quite rare. Herein, we report a rare coexistence of nephrolithiasis and acquired renal Fanconi syndrome in a chronic hepatitis B-positive patient with prolonged adefovir therapy. The patient presented with osteomalacia and nephrolithiasis. Consequently, extracorporeal shock-wave lithotripsy and left double-J ureteral stent insertion were considered for obstructive nephropathy, which was caused by nephrolithiasis. However, osteomalacia had been misdiagnosed as osteoporosis before admission to our hospital. On admission, a complexity of multiple fractures, hypophosphataemia, glycosuria without hyperglycaemia and non-anion-gap metabolic acidosis indicated a diagnosis of acquired renal Fanconi syndrome induced by adefovir. After switching from adefovir to entecavir, the patient's symptoms and laboratory findings improved significantly. The mechanism responsible for nephrolithiasis in renal Fanconi syndrome is still unclear. We recommend regularly monitoring renal function and serum calcium and serum phosphate to prevent renal Fanconi syndrome during the prolonged use of adefovir for hepatitis B virus.

Family physicians' knowledge and screening of chronic hepatitis and liver cancer.

PubMed

Ferrante, Jeanne M; Winston, Dock G; Chen, Ping-Hsin; de la Torre, Andrew N

2008-05-01

Studies show that primary care providers may suboptimally diagnose, treat, or refer patients with hepatitis C virus (HCV) infection. In addition, little is known about family physicians' knowledge and practices regarding chronic hepatitis B virus (HBV) infection or monitoring for hepatocellular carcinoma (HCC). We used a cross-sectional mail survey of members of the New Jersey Academy of Family Physicians (n=217). Outcome measures were knowledge of risk factors, screening, counseling for chronic HCV and HBV, and screening for HCC. Mean knowledge score for risk factors was 79% (HBV) and 70% (HCV). Physicians who diagnosed >or= six cases per year had higher knowledge of HBV risk factors. Physicians in practice >20 years had lower knowledge of HCV risk factors. Mean knowledge score for counseling was 77%. About 25% screened for liver cancer. Screening for HCC in patients with HBV was related to years in practice, female physicians, and group practice. Physicians in academic settings were more likely to screen patients with HCV for HCC. Forty-two percent and 51% referred patients with chronic HBV and chronic HCV, respectively, to the specialist for total management. Family physicians have insufficient knowledge about screening and counseling for chronic hepatitis and hepatocellular carcinoma.

Audio distribution and Monitoring Circuit

NASA Technical Reports Server (NTRS)

Kirkland, J. M.

1983-01-01

Versatile circuit accepts and distributes TV audio signals. Three-meter audio distribution and monitoring circuit provides flexibility in monitoring, mixing, and distributing audio inputs and outputs at various signal and impedance levels. Program material is simultaneously monitored on three channels, or single-channel version built to monitor transmitted or received signal levels, drive speakers, interface to building communications, and drive long-line circuits.

Mobile patient monitoring based on impedance-loaded SAW-sensors.

PubMed

Karilainen, Anna; Finnberg, Thomas; Uelzen, Thorsten; Dembowski, Klaus; Müller, Jörg

2004-11-01

A remotely requestable, passive, short-range sensor network for measuring small voltages is presented. The sensor system is able to simultaneously monitor six small voltages in millivolt-range, and it can be used for Holter-electrocardiogram (ECG) and other biopotential monitoring, or in industrial applications. The sensors are based on a surface acoustic wave (SAW) delay line with voltage-dependent, impedance loading on a reflector interdigital transducer (IDT). The load circuit impedance is varied by the capacitance of the voltage-controlled varactor. High resolution is achieved by developing a MOS-capacitor with a thin oxide, low flat-band voltage, and zero-voltage capacitance in the space-charge region, as well as a high-Q-microcoil by thick metal electroplating. Simultaneous monitoring of multiple potentials is realized by time-division-multiplexing of different sensor signals.

[Bilateral non-arteritic ischemic optic neuropathy during treatment of viral hepatitis C with pegylated interferon and Ribavirin].

PubMed

Iferkhass, S; Elasri, F; Chatioui, S; Khoyaali, A; Bargach, T; Reda, K; Oubaaz, A

2015-01-01

Hepatitis C is a serious viral infection, for which the current treatment is based on the combination of pegylated interferon (IFN) and Ribavirin(®). Ophthalmic complications observed with PEG-IFN are infrequent and of variable prognosis. They often include an ischemic retinopathy with typical cotton-wool spots, hemorrhage and retinal edema, and rarely acute non-arteritic anterior ischemic optic neuropathy as illustrated by our report. We report the case of a 51-year-old man followed for chronic active hepatitis C, who presented in the fourth month of treatment with pegylated interferon and vidarabine with a sharp decline in visual acuity secondary to acute bilateral non-arteritic anterior ischemic optic neuropathy. The hepatitis C treatment was discontinued. His course was notable by the third week for a significant regression of papilledema with improvement in visual acuity in the right eye and no change in the left eye, remaining at counting fingers. After regressing for four years, the disease progressed to bilateral temporal optic atrophy without change in visual acuity. Pegylated interferon and Ribavirin(®) are commonly used in the treatment of chronic hepatitis C. They are the source of various ophthalmologic complications of varied severity. The pathophysiology of this ocular toxicity currently remains hypothetical. Non-arteritic ischemic optic neuropathy is still a relatively rare complication with a poor functional prognosis, often requiring discontinuation of treatment. Thus, careful ophthalmologic monitoring before and during antiviral treatment of patients with hepatitis C appears necessary. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Surgical treatment of hepatic echinococcosis in Prizren (Kosovo)

PubMed Central

Avdaj, Afrim; Namani, Sadie

2014-01-01

Management option of hepatic echinococcosis represents a major challenge for a surgeon. The aim of the study was to evaluate surgical treatment of patients with hepatic echinococcosis at the surgery department of the regional hospital in Prizren (Kosovo). The medical records of 22 patients operated for hepatic echinococcosis in our department during a four year study period (2009–2013) were retrospectively reviewed. Apart from the total of 5850 operated patients, 22 cases were diagnosed for liver echinococcosis (0.4%). The most affected age group was from 26 to 50 years (54.5%). Female gender, 16 cases (73%), and patients living in rural places, 14 patients (64%), dominated significantly. The most affected region was Municipality of Dragash. All patients underwent ultrasonography, 13 patients underwent CT scans and 5 patients MRI of abdomen. The mean preoperative ultrasonographic diameter of cysts was 9.5 cm and maximal 21 cm. Cysts were most often localized in right hepatic lobe (77%) and subcostal laparotomy was most commonly performed (82%). The performed surgical procedures were: endocystectomy and partial pericystectomy with omentoplication according to Papadimitris (73%), endocystectomy and capitonnage and endocystectomy with external drainage (14%). The laparoscopic approach was used only in one patient. In conclusion, hepatic echinococosis was not common among operated patients at our surgery department. Subcostal laparotomy with endocystectomy and partial pericystectomy with omentoplication according to Papadimitris was most commonly used. Exact distribution of echinococcosis is needed to be analyzed with a larger cohort study including all surgery units in the country and with a longer monitoring. PMID:25568800

Probe Oscillation Shear Wave Elastography: Initial In Vivo Results in Liver.

PubMed

Mellema, Daniel C; Song, Pengfei; Kinnick, Randall R; Trzasko, Joshua D; Urban, Matthew W; Greenleaf, James F; Manduca, Armando; Chen, Shigao

2018-05-01

Shear wave elastography methods are able to accurately measure tissue stiffness, allowing these techniques to monitor the progression of hepatic fibrosis. While many methods rely on acoustic radiation force to generate shear waves for 2-D imaging, probe oscillation shear wave elastography (PROSE) provides an alternative approach by generating shear waves through continuous vibration of the ultrasound probe while simultaneously detecting the resulting motion. The generated shear wave field in in vivo liver is complicated, and the amplitude and quality of these shear waves can be influenced by the placement of the vibrating probe. To address these challenges, a real-time shear wave visualization tool was implemented to provide instantaneous visual feedback to optimize probe placement. Even with the real-time display, it was not possible to fully suppress residual motion with established filtering methods. To solve this problem, the shear wave signal in each frame was decoupled from motion and other sources through the use of a parameter-free empirical mode decomposition before calculating shear wave speeds. This method was evaluated in a phantom as well as in in vivo livers from five volunteers. PROSE results in the phantom as well as in vivo liver correlated well with independent measurements using the commercial General Electric Logiq E9 scanner.

76 FR 18553 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

.... Women Involved in Life Learning from Other Women (WILLOW) is an EBI that focuses on health education and.... Proposed Project Community-based Organization (CBO) Monitoring and Evaluation Project (CMEP) of Women Involved in Life Learning from Other Women (WILLOW)--New--National Center for HIV/AIDS, Viral Hepatitis...

77 FR 76045 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... System (NHSS) (OMB No. 0920-0573, Expiration 01/31/2013)-Revision- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Centers for Disease Control and Prevention (CDC). This title is... monitor patterns in viral resistance and HIV-1 subtypes, as well as provide information on perinatal...

77 FR 47848 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

..., Expiration 01/31/2013)-Revision- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention... national system provides essential data to estimate HIV incidence and monitor patterns in viral resistance... incidence, to better describe the extent of HIV viral resistance and quantify HIV subtypes among persons...

RAPID PCR-BASED MONITORING OF INFECTIOUS ENTEROVIRUSES IN DRINKING WATER. (R824756)

EPA Science Inventory

Abstract

Currently, the standard method for the detection of enteroviruses and hepatitis A virus in water involves cell culture assay which is expensive and time consuming. Direct RT-PCR offers a rapid and sensitive alternative to virus detection but sensitivity is oft...

40 CFR 63.2161 - What performance tests and other procedures must I use if I monitor brew ethanol?

Code of Federal Regulations, 2013 CFR

2013-07-01

... procedures must I use if I monitor brew ethanol? 63.2161 Section 63.2161 Protection of Environment... performance tests and other procedures must I use if I monitor brew ethanol? (a) You must conduct each... performance test simultaneously with brew ethanol monitoring to establish a brew-to-exhaust correlation...

40 CFR 63.2161 - What performance tests and other procedures must I use if I monitor brew ethanol?

Code of Federal Regulations, 2012 CFR

2012-07-01

... procedures must I use if I monitor brew ethanol? 63.2161 Section 63.2161 Protection of Environment... performance tests and other procedures must I use if I monitor brew ethanol? (a) You must conduct each... performance test simultaneously with brew ethanol monitoring to establish a brew-to-exhaust correlation...

40 CFR 63.2161 - What performance tests and other procedures must I use if I monitor brew ethanol?

Code of Federal Regulations, 2014 CFR

2014-07-01

... procedures must I use if I monitor brew ethanol? 63.2161 Section 63.2161 Protection of Environment... performance tests and other procedures must I use if I monitor brew ethanol? (a) You must conduct each... performance test simultaneously with brew ethanol monitoring to establish a brew-to-exhaust correlation...

Real-time monitoring implementation in a remote-pumped WDM PON

NASA Astrophysics Data System (ADS)

Liaw, S.-K.; Hong, K.-L.; Shei, Y.-S.

2008-08-01

We report on an improved configuration to monitor a passive optical network with high quality in service. This proposed system comprises fiber-Bragg gratings, a 1 × 4 optical switch, and an optical time-domain reflectometry to diagnose the broken point in real time. It could simultaneously detect multioptical network units in a WDM PON. The remote-pump integrated residual pumping reused function is implemented. Broken points in different optical paths can be detected simultaneously even when the distances to the central office are identical. The bit-error rate testing is verified with a small power penalty, making it an ideal solution for the real-time monitoring in a WDM PON.

Citizen Science Air Monitor (CSAM) Operating Procedures

EPA Science Inventory

The Citizen Science Air Monitor (CSAM) is an air monitoring system designed for measuring nitrogen dioxide (NO2) and particulate matter (PM) pollutants simultaneously. This self-contained system consists of a CairPol CairClip NO2 sensor, a Thermo Scientific personal DataRAM PM2.5...

Metabolic cytometry: capillary electrophoresis with two-color fluorescence detection for the simultaneous study of two glycosphingolipid metabolic pathways in single primary neurons.

PubMed

Essaka, David C; Prendergast, Jillian; Keithley, Richard B; Palcic, Monica M; Hindsgaul, Ole; Schnaar, Ronald L; Dovichi, Norman J

2012-03-20

Metabolic cytometry is a form of chemical cytometry wherein metabolic cascades are monitored in single cells. We report the first example of metabolic cytometry where two different metabolic pathways are simultaneously monitored. Glycolipid catabolism in primary rat cerebella neurons was probed by incubation with tetramethylrhodamine-labeled GM1 (GM1-TMR). Simultaneously, both catabolism and anabolism were probed by coincubation with BODIPY-FL labeled LacCer (LacCer-BODIPY-FL). In a metabolic cytometry experiment, single cells were incubated with substrate, washed, aspirated into a capillary, and lysed. The components were separated by capillary electrophoresis equipped with a two-spectral channel laser-induced fluorescence detector. One channel monitored fluorescence generated by the metabolic products produced from GM1-TMR and the other monitored the metabolic products produced from LacCer-BODIPY-FL. The metabolic products were identified by comparison with the mobility of a set of standards. The detection system produced at least 6 orders of magnitude dynamic range in each spectral channel with negligible spectral crosstalk. Detection limits were 1 zmol for BODIPY-FL and 500 ymol for tetramethylrhodamine standard solutions.

Sexually transmitted infections and PRO-LIVES: based on a clinical report*

PubMed Central

Velho, Paulo Eduardo Neves Ferreira

2017-01-01

Physicians are also responsible for the increase in sexually transmitted infections. We report a case of patient inadequately monitored, that shows the importance of physicians to take basic measures with any individual at risk of acquiring such infections. We propose the following mnemonic acrostic: PRO-LIVES (Protection: usual and proper codom use, Responsibility, Other orientations, Laboratory tests -HIV infection, syphilis and B and C hepatitis-, Immunization: B hepatitis vaccination, Various: at least two patients, Ensure: case history and physical examination, Single dose treatment: whenever possible). Clinicians should take these measures when treating any patient who has been exposed to risk or with a diagnosis of sexually transmitted infections. PMID:28538901

Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases

PubMed Central

Li, Sha; Hong, Ming

2016-01-01

The crucial roles of oxidative stress and inflammation in the development of hepatic diseases have been unraveled and emphasized for decades. From steatosis to fibrosis, cirrhosis and liver cancer, hepatic oxidative stress, and inflammation are sustained and participated in this pathological progressive process. Notably, increasing evidences showed that oxidative stress and inflammation are tightly related, which are regarded as essential partners that present simultaneously and interact with each other in various pathological conditions, creating a vicious cycle to aggravate the hepatic diseases. Clarifying the interaction of oxidative stress and inflammation is of great importance to provide new directions and targets for developing therapeutic intervention. Herein, this review is concerned with the regulation and interdependence of oxidative stress and inflammation in a variety of liver diseases. In addition to classical mediators and signaling, particular emphasis is placed upon immune suppression, a potential linkage of oxidative stress and inflammation, to provide new inspiration for the treatment of liver diseases. Furthermore, since antioxidation and anti-inflammation have been extensively attempted as the strategies for treatment of liver diseases, the application of herbal medicines and their derived compounds that protect liver from injury via regulating oxidative stress and inflammation collectively were reviewed and discussed. PMID:28070230

Impact of specialty pharmacy on telaprevir-containing 3-drug hepatitis C regimen persistence.

PubMed

Henderson, Rochelle R; Visaria, Jay; Bridges, Gail G; Dorholt, Mary; Levin, Rebecca J; Frazee, Sharon Glave

2014-12-01

Although the recommended treatment of hepatitis C continues to evolve as newer and more effective medications are made available, hepatitis C drug regimens consisting of a 3-drug combination of a protease inhibitor, pegylated interferon, and ribavirin were recommended by the American Association for the Study of Liver Diseases for the HCV genotype I beginning in 2011. Although more effective than the earlier standard of care, these regimens have complex dosing schedules, prolonged duration, and deleterious side effects. It has been shown that patients tend to discontinue these regimens prematurely. Specialty pharmacies offer specialized care management programs to hepatitis C patients, consisting of such services as regularly scheduled patient counseling, assessing regimen appropriateness, monitoring treatment progress, scheduling refill reminders, and coordinating patient care with prescribers. The use of specialty pharmacies by hepatitis C patients may improve persistence on the 3-drug hepatitis C regimens. To examine the association of pharmacy dispensing channel (specialty pharmacy or retail pharmacy) and hepatitis C regimen persistence among patients on a 3-drug hepatitis C regimen containing telaprevir, a widely used hepatitis C protease inhibitor.  A retrospective, observational study was conducted using pharmacy claims data from a national pharmacy benefits manager for the period July 2011 to June 2013. Continuously eligible patients who started a new 3-drug regimen containing telaprevir were included in the study and followed for up to 12 months after the index hepatitis C claim. The study outcome was persistence to the 3-drug regimen at treatment week 24 (day 168), representing the completion of an important milestone in the regimen. Patients were defined as persistent if they filled 84 days' supply of telaprevir and 168 days' supply of pegylated interferon and ribavirin each, as required by the regimen protocol. Multivariate logistic regression was used to evaluate the association between dispensing channel and persistence, controlling for differences in demographics, medication burden, out-of-pocket spend per 30-day adjusted hepatitis C prescription, and average days' supply per unadjusted hepatitis C prescription. The final study sample consisted of 1,475 patients-1,182 in the specialty pharmacy group and 293 in the retail pharmacy group. A significantly greater proportion of patients were persistent to the 3-drug hepatitis C regimen containing telaprevir in specialty pharmacy, compared with retail pharmacy (56.0% vs. 39.9%, P  less than  0.001). After multivariate adjustment, patients in the specialty pharmacy group had 1.89 times greater odds of being persistent to 3-drug hepatitis C regimens containing telaprevir compared with patients in the retail group (95% CI=1.44-2.48). Patients who used a specialty pharmacy offering refill reminders, care management, and care coordination with prescribers were significantly more likely to be persistent to 3-drug hepatitis C regimens, compared with patients using a retail pharmacy.

Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills.

PubMed

Sandmeier, Peter; Clauss, Marcus; Donati, Olivio F; Chiers, Koen; Kienzle, Ellen; Hatt, Jean-Michel

2012-01-01

3 hornbills (2 Papua hornbills [Aceros plicatus] and 1 longtailed hornbill [Tockus albocristatus]) were evaluated because of general listlessness and loss of feather glossiness. Because hepatic iron storage disease was suspected, liver biopsy was performed and formalin-fixed liver samples were submitted for histologic examination and quantitative image analysis (QIA). Additional frozen liver samples were submitted for chemical analysis. Birds also underwent magnetic resonance imaging (MRI) under general anesthesia for noninvasive measurement of liver iron content. Serum biochemical analysis and analysis of feed were also performed. Results of diagnostic testing indicated that all 3 hornbills were affected with hepatic iron storage disease. The iron chelator deferiprone was administered (75 mg/kg [34.1 mg/lb], PO, once daily for 90 days). During the treatment period, liver biopsy samples were obtained at regular intervals for QIA and chemical analysis of the liver iron content and follow-up MRI was performed. In all 3 hornbills, a rapid and large decrease in liver iron content was observed. All 3 methods for quantifying the liver iron content were able to verify the decrease in liver iron content. Orally administered deferiprone was found to effectively reduce the liver iron content in these 3 hornbills with iron storage disease. All 3 methods used to monitor the liver iron content (QIA, chemical analysis of liver biopsy samples, and MRI) had similar results, indicating that all of these methods should be considered for the diagnosis of iron storage disease and monitoring of liver iron content during treatment.

Atlas-based liver segmentation and hepatic fat-fraction assessment for clinical trials.

PubMed

Yan, Zhennan; Zhang, Shaoting; Tan, Chaowei; Qin, Hongxing; Belaroussi, Boubakeur; Yu, Hui Jing; Miller, Colin; Metaxas, Dimitris N

2015-04-01

Automated assessment of hepatic fat-fraction is clinically important. A robust and precise segmentation would enable accurate, objective and consistent measurement of hepatic fat-fraction for disease quantification, therapy monitoring and drug development. However, segmenting the liver in clinical trials is a challenging task due to the variability of liver anatomy as well as the diverse sources the images were acquired from. In this paper, we propose an automated and robust framework for liver segmentation and assessment. It uses single statistical atlas registration to initialize a robust deformable model to obtain fine segmentation. Fat-fraction map is computed by using chemical shift based method in the delineated region of liver. This proposed method is validated on 14 abdominal magnetic resonance (MR) volumetric scans. The qualitative and quantitative comparisons show that our proposed method can achieve better segmentation accuracy with less variance comparing with two other atlas-based methods. Experimental results demonstrate the promises of our assessment framework. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study of hepatitis B virus gene mutations with enzymatic colorimetry-based DNA microarray.

PubMed

Mao, Hailei; Wang, Huimin; Zhang, Donglei; Mao, Hongju; Zhao, Jianlong; Shi, Jian; Cui, Zhichu

2006-01-01

To establish a modified microarray method for detecting HBV gene mutations in the clinic. Site-specific oligonucleotide probes were immobilized to microarray slides and hybridized to biotin-labeled HBV gene fragments amplified from two-step PCR. Hybridized targets were transferred to nitrocellulose membranes, followed by intensity measurement using BCIP/NBT colorimetry. HBV genes from 99 Hepatitis B patients and 40 healthy blood donors were analyzed. Mutation frequencies of HBV pre-core/core and basic core promoter (BCP) regions were found to be significantly higher in the patient group (42%, 40% versus 2.5%, 5%, P < 0.01). Compared with a traditional fluorescence method, the colorimetry method exhibited the same level of sensitivity and reproducibility. An enzymatic colorimetry-based DNA microarray assay was successfully established to monitor HBV mutations. Pre-core/core and BCP mutations of HBV genes could be major causes of HBV infection in HBeAg-negative patients and could also be relevant to chronicity and aggravation of hepatitis B.

Systematic review of severe acute liver injury caused by terbinafine.

PubMed

Yan, Jun; Wang, Xiaolin; Chen, Shengli

2014-08-01

Terbinafine is an effective antimicrobial agent against dermatophytes, cryptococcus and other fungi. It is the preferred drug to treat onychomycosis. However, severe acute hepatitis from oral terbinafine administration has been recently reported. To describe a representative case, and review the literature regarding the best evidence on treatment and prognosis of severe acute hepatitis caused by oral terbinafine. The literature was searched for publications on severe hepatitis caused by terbinafine using MEDLINE, China Biology Medicine Disc, and the VIP Medical Information Resource System. Related references were searched manually. Seventeen English and three Chinese references of case reports were included after eliminating duplicate publications. No randomized control studies were found. Liver enzyme levels were found to have been increased significantly. Abdominal ultrasound demonstrated cholestasis. Severe acute liver injury is a known, but unusual complication of terbinafine exposure. The prognosis is often good with appropriate treatment. Liver function assessment before treatment and periodic monitoring 4-6 weeks after initiation of treatment is recommended.

Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure.

PubMed

Colpitts, Che C; Baumert, Thomas F

2016-08-16

Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

Expanding access to transplantation with hepatitis C-positive donors: A new perspective on an old issue.

PubMed

Kling, Catherine E; Limaye, Ajit P; Landis, Charles S; Sibulesky, Lena

2017-02-01

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody-positive (HBcAb+) donors into select recipients, in the era of direct-acting antivirals (DAAs), a new focus should be placed on HCV-positive donors. The transmission rate from HCV antibody-positive (HCVAb+) nucleic acid testing negative (HCV NAT-) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post-transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post-transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MARVEL: A knowledge-based productivity enhancement tool for real-time multi-mission and multi-subsystem spacecraft operations

NASA Astrophysics Data System (ADS)

Schwuttke, Ursula M.; Veregge, John, R.; Angelino, Robert; Childs, Cynthia L.

1990-10-01

The Monitor/Analyzer of Real-time Voyager Engineering Link (MARVEL) is described. It is the first automation tool to be used in an online mode for telemetry monitoring and analysis in mission operations. MARVEL combines standard automation techniques with embedded knowledge base systems to simultaneously provide real time monitoring of data from subsystems, near real time analysis of anomaly conditions, and both real time and non-real time user interface functions. MARVEL is currently capable of monitoring the Computer Command Subsystem (CCS), Flight Data Subsystem (FDS), and Attitude and Articulation Control Subsystem (AACS) for both Voyager spacecraft, simultaneously, on a single workstation. The goal of MARVEL is to provide cost savings and productivity enhancement in mission operations and to reduce the need for constant availability of subsystem expertise.

Nondestructive assessment of waveguides using an integrated electromechanical impedance and ultrasonic waves approach

NASA Astrophysics Data System (ADS)

Nasrollahi, Amir; Ma, Zhaoyun; Rizzo, Piervincenzo

2017-04-01

In this paper we present a structural health monitoring (SHM) paradigm based on the simultaneous use of ultrasounds and electromechanical impedance (EMI) to monitor waveguides. The paradigm uses guided ultrasonic waves (GUWs) in pitch-catch mode and EMI simultaneously. The two methodologies are driven by the same sensing/hardware/software unit. To assess the feasibility of this unified system an aluminum plate was monitored for varying damage location. Damage was simulated by adding small masses to the plate. The results associated with pitch-catch GUW testing mode were used in ultrasonic tomography, and statistical analysis was used to detect the damages using the EMI measurements. The results of GUW and EMI monitoring show that the proposed system is robust and can be developed further to address the challenges associated with the SHM of complex structures.

Ameliorative effect of vitamin E on hepatic oxidative stress and hypoimmunity induced by high-fat diet in turbot (Scophthalmus maximus).

PubMed

Jia, Yudong; Jing, Qiqi; Niu, Huaxin; Huang, Bin

2017-08-01

This study was conducted to examine the effects of vitamin E on growth performance, oxidative stress and non-specific immunity of turbot (Scophthalmus maximus) fed with high-fat diet. Results showed that high-fat diet significantly increased hepatosomatic index, viscerosomatic index, hepatic malondialdehyde level and decreased catalase and superoxide dismutase activities, whereas final weight, specific growth rate and survival rate remained unchanged. Meanwhile, nitro blue tetrazolium positive leucocytes of head kidney, respiratory burst activity in head-kidney macrophage, phagocytic index and serum lysozyme activity were significantly reduced after feeding with high-fat diet. Furthermore, fish fed with high-fat diet promoted higher expression of heat shock protein (hsp70, hsp90), and inhibited expression of complement component 3 (c3) in the liver and tumor necrosis factor-α (tnf-α), interleukine 1β (il-1β), toll like receptor 22 (tlr-22) in the spleen and head-kidney, respectively. However, simultaneous supplementation with 480 mg kg -1 vitamin E protected turbot against high-fat diet-induced hepatic oxidative stress, hypoimmunity through attenuating lipid peroxidation, renewing antioxidant enzymes activities and nonspecific immune responses, and modulating the expression of stress protein (hsp70, hsp90) and immune-related genes (c3, tnf-α, il-1β, tlr-22). In conclusion, the obtained results indicate the vitamin E as a wildly used functional feed additive contributes potentially to alleviate high-fat diet-induced hepatic oxidative stress and hypoimmunity, maintain the health, and improve the broodstock management for turbot. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of clinical sensitivity and specificity of hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency Virus-1 by cobas MPX: Detection of occult HBV infection in an HBV-endemic area.

PubMed

Ha, Jihye; Park, Younhee; Kim, Hyon-Suk

2017-11-01

Transfusion-transmitted infectious diseases remain a major concern for blood safety, particularly with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Nucleic acid testing (NAT) in donor screening shortens the serologically negative window period and reduces virus transmission. The cobas MPX (Roche Molecular Systems, Inc., Branchburg, New Jersey) is a recently developed multiplex qualitative PCR system that enables the simultaneous detection of HBV, HCV, and HIV with improved sensitivity and throughput using cobas 6800 and 8800 instruments. The aim of this study was to conduct an evaluation of the clinical sensitivity and specificity of cobas MPX detection of HBV, HCV, and HIV in clinical specimens. Among samples referred for HBV, HCV, and HIV-1 quantification at Severance Hospital, Yonsei University College of Medicine, positive samples were selected to evaluate sensitivity. A total of 843 samples was tested using both cobas MPX and COBAS AmpliPrep/COBAS TaqMan Tests for HBV, HCV, and HIV-1 using the cobas 8800 system and a COBAS TaqMan 96 analyzer, respectively. Samples that showed discrepancies were confirmed by nested PCR. The cobas MPX achieved excellent sensitivity and specificity for the detection of HBV, HCV, and HIV-1 in clinical samples. We found that the lower limit of detection (LOD) of blood screening by NAT actually improves clinical sensitivity, and occult HBV infection prevalence among healthy employees of the hospital was rather high. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a One-Step Duplex RT-PCR Method for the Simultaneous Detection of VP3/VP1 and VP1/P2B Regions of the Hepatitis A Virus.

PubMed

Kim, Mi-Ju; Lee, Shin-Young; Kim, Hyun-Joong; Lee, Jeong Su; Joo, In Sun; Kwak, Hyo Sun; Kim, Hae-Yeong

2016-08-28

The simultaneous detection and accurate identification of hepatitis A virus (HAV) is critical in food safety and epidemiological studies to prevent the spread of HAV outbreaks. Towards this goal, a one-step duplex reverse-transcription (RT)-PCR method was developed targeting the VP1/P2B and VP3/VP1 regions of the HAV genome for the qualitative detection of HAV. An HAV RT-qPCR standard curve was produced for the quantification of HAV RNA. The detection limit of the duplex RT-PCR method was 2.8 × 10(1) copies of HAV. The PCR products enabled HAV genotyping analysis through DNA sequencing, which can be applied for epidemiological investigations. The ability of this duplex RT-PCR method to detect HAV was evaluated with HAV-spiked samples of fresh lettuce, frozen strawberries, and oysters. The limit of detection of the one-step duplex RT-PCR for each food model was 9.4 × 10(2) copies/20 g fresh lettuce, 9.7 × 10(3) copies/20 g frozen strawberries, and 4.1 × 10(3) copies/1.5 g oysters. Use of a one-step duplex RT-PCR method has advantages such as shorter time, decreased cost, and decreased labor owing to the single amplification reaction instead of four amplifications necessary for nested RT-PCR.

Vaccine adverse events in the new millennium: is there reason for concern?

PubMed Central

Ward, B. J.

2000-01-01

As more and more infectious agents become targets for immunization programmes, the spectrum of adverse events linked to vaccines has been widening. Although some of these links are tenuous, relatively little is known about the immunopathogenesis of even the best characterized vaccine-associated adverse events (VAAEs). The range of possible use of active immunization is rapidly expanding to include vaccines against infectious diseases that require cellular responses to provide protection (e.g. tuberculosis, herpes viral infections), therapeutic vaccines for chronic infections (e.g. human immunodeficiency virus (HIV) infection, viral hepatitis B and C), and vaccines against non-infectious conditions (e.g. cancer, autoimmune diseases). Less virulent pathogens (e.g. varicella, rotavirus in the developed world) are also beginning to be targeted, and vaccine use is being justified in terms of societal and parental "costs" rather than in straightforward morbidity and mortality costs. In the developed world the paediatric immunization schedule is becoming crowded, with pressure to administer increasing numbers of antigens simultaneously in ever simpler forms (e.g. subcomponent, peptide, and DNA vaccines). This trend, while attractive in many ways, brings hypothetical risks (e.g. genetic restriction, narrowed shield of protection, and loss of randomness), which will need to be evaluated and monitored. The available epidemiological and laboratory tools to address the issues outlined above are somewhat limited. As immunological and genetic tools improve in the years ahead, it is likely that we shall be able to explain the immunopathogenesis of many VAAEs and perhaps even anticipate and avoid some of them. However, this will only happen if the human and financial resources needed for monitoring and studying vaccine safety stay in step with the accelerating pace of vaccine development. Failure to make such a commitment would put all immunization programmes at risk. PMID:10743286

High-resolution mass spectrometry of skin mucus for monitoring physiological impacts and contaminant biotransformation products in fathead minnows exposed to wastewater effluent.

PubMed

Mosley, Jonathan D; Ekman, Drew R; Cavallin, Jenna E; Villeneuve, Daniel L; Ankley, Gerald T; Collette, Timothy W

2018-03-01

High-resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales promelas) exposed to control water or treated wastewater effluent at 5, 20, and 100% levels for 21 d, using an on-site, flow-through system providing real-time exposure. Both sex-specific and non-sex-specific responses were observed in the mucus metabolome, the latter suggesting the induction of general compensatory pathways for xenobiotic exposures. Altogether, 85 statistically significant treatment-dependent metabolite changes were observed out of the 310 total endogenous metabolites that were detected (156 of the 310 were annotated). Partial least squares-regression models revealed strong covariances between the mucus metabolomes and up-regulated hepatic messenger ribonucleic acid (mRNA) transcripts reported previously for these same fish. These regression models suggest that mucus metabolomic changes reflected, in part, processes by which the fish biotransformed xenobiotics in the effluent. In keeping with this observation, we detected a phase II transformation product of bisphenol A in the skin mucus of male fish. Collectively, these findings demonstrate the utility of mucus as a minimally invasive matrix for simultaneously assessing exposures and effects of environmentally relevant mixtures of contaminants. Environ Toxicol Chem 2018;37:788-796. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

42 CFR 494.50 - Condition: Reuse of hemodialyzers and bloodlines.

Code of Federal Regulations, 2013 CFR

2013-10-01

...— (1) May be reused for certain patients with the exception of Hepatitis B positive patients; (2) Must... reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. This publication is available for inspection... the facility. (c) Standard: Monitoring, evaluation, and reporting requirements for the reuse of...

42 CFR 494.50 - Condition: Reuse of hemodialyzers and bloodlines.

Code of Federal Regulations, 2014 CFR

2014-10-01

...— (1) May be reused for certain patients with the exception of Hepatitis B positive patients; (2) Must... reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. This publication is available for inspection... the facility. (c) Standard: Monitoring, evaluation, and reporting requirements for the reuse of...

42 CFR 494.50 - Condition: Reuse of hemodialyzers and bloodlines.

Code of Federal Regulations, 2012 CFR

2012-10-01

...— (1) May be reused for certain patients with the exception of Hepatitis B positive patients; (2) Must... reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. This publication is available for inspection... the facility. (c) Standard: Monitoring, evaluation, and reporting requirements for the reuse of...

Comparative Sensor Fusion between Hyperspectral and Multispectral Remote Sensing Data for Monitoring Microcystin Distribution in Lake Erie

EPA Science Inventory

Urban growth and agricultural production have caused an influx of nutrients into Lake Erie, leading to eutrophic zones. These conditions result in the formation of algal blooms, some of which are toxic due to the presence of Microcystis (a cyanobacteria), which produces the hepat...

42 CFR 494.50 - Condition: Reuse of hemodialyzers and bloodlines.

Code of Federal Regulations, 2010 CFR

2010-10-01

...— (1) May be reused for certain patients with the exception of Hepatitis B positive patients; (2) Must... CFR 876.5860. (b) Standard: Reprocessing requirements for the reuse of hemodialyzers and bloodlines. A... paragraphs (a) and (b) of this section, the dialysis facility must adhere to the following: (1) Monitor...

Induction of hepatic haematopoiesis with fibronectin expression by EMT stromal cells during the second trimester of development.

PubMed

Lambropoulou, M; Tamiolakis, D; Venizelos, I; Alexiadis, G; Anastasopoulos, G; Limberis, V; Galazios, G; Tsikouras, P; Simopoulou, M; Nikolaidou, S; Petrakis, G; Papadopoulos, N

2007-09-01

In an initial period of vertebrate phylogeny (bone marrow-less vertebrates), lymphohaematopoiesis takes place in numerous organs containing a suitable microenvironment. Among other organs (i.e., gonads, kidney and spleen), the liver is apparently the most appropriate site for homing and differentiation of haematopoietic cell precursors. Interaction between haematopoietic cells and stromal cells is important for regulation of haematopoiesis. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about the effect of the foetal hepatic epithelial-to-mesenchymal transition (EMT) stromal cells' activity and their product-fibronectin, on foetal hepatic haematopoiesis. The binding of late-stage erythroid cells to FN has been well characterised and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to provide a quantitative overview of FN, produced by hepatic EMT stromal cells, in foetal hepatic haematopoiesis during the first and second trimester of development. Paraffin-embedded specimens from the liver of 30 human embryos in the first and second trimesters of gestation were investigated by conventional histology and immunohistology for the presence of FN and specific haematopoietic cell types. The staining intensity, and localisation of FN and haematopoietic markers in sequential sections were examined. Furthermore, double immunohistochemical staining was performed to assess simultaneous detection of FN and haematopoietic markers. FN was expressed in the EMT stromal cells of the hepatic portal triads more strongly during the second trimester than the first. Furthermore, an intense immunostaining for haematopoietic lineages, and especially for erythropoiesis, was observed in the second trimester compared to the first. The results of the double immunostaining disclosed an intimate co-expression of the FN and CD haematopoietic markers. Foetal hepatic EMT stromal cells provide a unique microenvironment that supports the emergence, expansion and maintenance of human foetal haematopoietic development during the mid-gestational stage. FN produced by the EMT stromal cells follows a time course parallel to that of haematopoiesis. We suggest that in foetal liver, phenotypic modifications of EMT stromal cells expressing FN concerning the cell adhesion capacity of the protein are associated with proliferation and differentiation of specific haematopoietic cell lineages during the second trimester of gestation, probably reflecting the increasing demand of the growing foetus for mature erythroid and myeloid cells.

Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers.

PubMed

Yeh, Rosa F; Gaver, Vincent E; Patterson, Kristine B; Rezk, Naser L; Baxter-Meheux, Faustina; Blake, Michael J; Eron, Joseph J; Klein, Cheri E; Rublein, John C; Kashuba, Angela D M

2006-05-01

The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail. Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) activities were evaluated using warfarin (WARF) + vitamin K, omeprazole (OMP), intravenous (IV) and oral (PO) midazolam (MDZ), and caffeine (CAF). : Open-label, multiple-dose, pharmacokinetic study in healthy volunteers. Subjects (n = 14) simultaneously received PO WARF 10 mg, vitamin K 10 mg, OMP 40 mg, CAF 2 mg/kg, and IV MDZ 0.025 mg/kg on days (D) 1 and 14, and PO MDZ 5 mg on D2 and D15. LPV/r (400/100 mg twice daily) was administered on D4-17. CYP2C9 and CYP2C19 activities were quantified by S-WARF AUC0-inf and OMP/5-hydroxy OMP ratio, respectively. CYP1A2, NAT-2, and XO activities were quantified by urinary CAF metabolite ratios. Hepatic and intestinal + hepatic CYP3A activities were quantified by IV (CL) and PO (CL/F) MDZ clearance, respectively. After LPV/r therapy, CYP2C9, CYP2C19, and CYP1A2 activity increased by 29%, 100%, and 43% (P = 0.001, 0.046, and 0.001), respectively. No changes were seen in NAT-2 or XO activity. Hepatic and intestinal + hepatic CYP3A activity decreased by 77% (P < 0.001) and 92% (P = 0.001), respectively. LPV/r therapy results in modest induction of CYP1A2 and CYP2C9 and potent induction of CYP2C19 activity. Increasing doses of concomitant medications metabolized by these enzymes may be necessary. LPV/r inhibited intestinal CYP3A to a greater extent than hepatic CYP3A activity. Doses of concomitant CYP3A substrates should be reduced when combined with LPV/r, although intravenously administered compounds may require less of a relative dose reduction than orally administered compounds.

Simultaneous Authentication and Certification of Arms-Control Measurement Systems

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

MacArthur, Duncan W.; Hauck, Danielle K.; Thron, Jonathan L.

2012-07-09

Most arms-control-treaty-monitoring scenarios involve a host party that makes a declaration regarding its nuclear material or items and a monitoring party that verifies that declaration. A verification system developed for such a use needs to be trusted by both parties. The first concern, primarily from the host party's point of view, is that any sensitive information that is collected must be protected without interfering in the efficient operation of the facility being monitored. This concern is addressed in what can be termed a 'certification' process. The second concern, of particular interest to the monitoring party, is that it must bemore » possible to confirm the veracity of both the measurement system and the data produced by this measurement system. The monitoring party addresses these issues during an 'authentication' process. Addressing either one of these concerns independently is relatively straightforward. However, it is more difficult to simultaneously satisfy host party certification concerns and monitoring party authentication concerns. Typically, both parties will want the final access to the measurement system. We will describe an alternative approach that allows both parties to gain confidence simultaneously. This approach starts with (1) joint development of the measurement system followed by (2) host certification of several copies of the system and (3) random selection by the inspecting party of one copy to be use during the monitoring visit and one (or more) copy(s) to be returned to the inspecting party's facilities for (4) further hardware authentication; any remaining copies are stored under joint seal for use as spares. Following this process, the parties will jointly (5) perform functional testing on the selected measurement system and then (6) use this system during the monitoring visit. Steps (1) and (2) assure the host party as to the certification of whichever system is eventually used in the monitoring visit. Steps (1), (3), (4), and (5) increase the monitoring party's confidence in the authentication of the measurement system.« less

Orlistat-induced fulminant hepatic failure.

PubMed

Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

2014-12-01

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

Sociocultural factors that potentially affect the institution of prevention and treatment strategies for prevention of hepatitis B in Chinese Canadians.

PubMed

Wu, Harry; Yim, Colina; Chan, Alex; Ho, Michael; Heathcote, Jenny

2009-01-01

Despite the availability of screening for chronic hepatitis B (CHB) infection and effective treatments now available, many at-risk individuals fail to seek appropriate medical attention. To identify the barriers to care for CHB infection in a Chinese Canadian community. A survey conducted in English or Chinese collected information from individuals with CHB infection that evaluated the level of understanding and identified the barriers that may prevent Chinese patients from undergoing monitoring, screening and/or treatment for CHB infection. Among the 204 patients enrolled, common misconceptions were that sharing food transmits hepatitis B and that patients with severe disease are always symptomatic. Patients with a better understanding of hepatitis B were better educated, younger and were being followed at a tertiary care centre (P<0.01 for all). Prominent barriers to health care were time, inconvenience and language difficulties. Patients under the care of family physicians who had extended office hours were less likely to cite time (P=0.06) and distance (P=0.05) as barriers. Patient misconceptions that severe liver disease due to hepatitis B infection is symptomatic may factor into the unwillingness to spare the time and undergo the inconvenience associated with regular medical follow-up. Implementation of programs that increase awareness of the silent progression of CHB infection and provide culturally responsive clinics, better able to work within patients' time constraints may improve Chinese patients' access to health care.

Impaired hepatic Gd-EOB-DTPA enhancement after radioembolisation of liver malignancies.

PubMed

Powerski, Maciej Janusz; Scheurig-Münkler, Christian; Hamm, Bernd; Gebauer, Bernhard

2014-08-01

To evaluate the uptake of the liver-specific magnetic resonance imaging (MRI) contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by functional liver parenchyma after radioembolisation (RE) of hepatic malignancies. Uptake of Gd-EOB-DTPA prior to RE versus 60+/-24d and 126+/-32d after RE was compared in a group of 33 patients with primary or secondary hepatic malignancies. In patients who underwent single-lobe treatment, left and right lobes were compared 59+/-24 days after RE. Gd-EOB-DTPA uptake was determined as follows: ratio of mean signal intensity in liver parenchyma to muscle in Gd-EOB-DTPA-enhanced T1-weighted MRI was subtracted from ratio of mean intensity in liver parenchyma to muscle in unenhanced T1-weighted MRI. Gd-EOB-DTPA uptake in liver parenchyma was 0.845+/-0.29 before RE, 0.615+/-0.38 (P = 0.0022) at day 60+/-24, and 0.739+/-0.30 at day 126+/-32 after RE. In cases of single-lobe treatment, Gd-EOB-DTPA uptake was 0.581+/-0.256 for treated and 0.828+/-0.32 (P = 0.0164) for untreated hepatic lobes. Uptake of Gd-EOB-DTPA by liver parenchyma is impaired after RE, indicating dysfunction of the local hepatic system. These findings suggest that Gd-EOB-DTPA-enhanced MRI has the potential to be used for monitoring liver damage after RE. © 2014 The Royal Australian and New Zealand College of Radiologists.

Development of a murine model of blunt hepatic trauma.

PubMed

Nemzek-Hamlin, Jean A; Hwang, Haejin; Hampel, Joseph A; Yu, Bi; Raghavendran, Krishnan

2013-10-01

Despite the prevalence of blunt hepatic trauma in humans, there are few rodent models of blunt trauma that can be used to study the associated inflammatory responses. We present a mouse model of blunt hepatic trauma that was created by using a cortical contusion device. Male mice were anesthetized with ketamine-xylazine-buprenorphine and placed in left lateral recumbency. A position of 2 mm ventral to the posterior axillary line and 5 mm caudal to the costal margin on the right side was targeted for impact. An impact velocity of 6 m/s and a piston depth of 12 mm produced a consistent pattern of hepatic injury with low mortality. All mice that recovered from anesthesia survived without complication for the length of the study. Mice were euthanized at various time points (n = 5 per group) until 7 d after injury for gross examination and collection of blood and peritoneal lavage fluids. Some mice were reanesthetized for serial monitoring of hepatic lesions via MRI. At 2 h after trauma, mice consistently displayed laceration, hematoma, and discoloration of the right lateral and caudate liver lobes, with intraabdominal hemorrhage but no other gross injuries. Blood and peritoneal lavage fluid were collected from all mice for cytokine analysis. At 2 h after trauma, there were significant increases in plasma IL10 as well as peritoneal lavage fluid IL6 and CXCL1/KC; however, these levels decreased within 24 h. At 7 d after trauma, the mice had regained body weight, and the hepatic lesions, which initially had increased in size during the first 48 h, had returned to their original size. In summary, this technique produced a reliable, low mortality, murine model that recreates features of blunt abdominal liver injury in human subjects with similar acute inflammatory response.

Prevention of infection-related cancers in the WHO Western Pacific Region.

PubMed

Shin, Hai-Rim; Shin, Aesun; Woo, Hyeongtaek; Fox, Kimberley; Walsh, Nick; Lo, Ying-Ru; Wiesen, Eric; Varghese, Cherian

2016-01-01

A considerable number of infectious agents have been classified as human carcinogens Group 1 by the International Agency for Research on Cancer. Major infection-related cancers such as cancers of nasopharynx (53%), stomach (60%) and liver (63%) occur in the World Health Organization Western Pacific Region. Many infection-related cancers are preventable, particularly those associated with human papilloma virus, Helicobacter pylori, human immunodeficiency virus-I, hepatitis B virus and hepatitis C virus and liver flukes. Mongolia shows the highest prevalence of hepatitis B virus and hepatitis C virus, and China shows the highest prevalence of Helicobacter pylori. Chronic infection is attributable for 17-28% of overall cancer incidence or mortality in China, Japan and Korea. Through infant immunization for hepatitis B, 30 of 37 countries and areas in the Western Pacific Region have reached the 2012 milestone of chronic hepatitis B virus infection prevalence of <2% in 5-year-old children and countries and areas of the region are now striving toward reaching the regional goal of <1% by 2017. Human papilloma virus immunization program is implemented either by government funding or, in some low-income countries, by public and private sector organizations. Cervical cancer screening via visual inspection with acetic acid or Pap smear is available in many Western Pacific Region Member States. More efforts are needed to implement new World Health Organization guide to vaccinate 9- to 13-year-old girls with two doses of human papilloma virus vaccine, and use human papilloma virus tests to screen women to prevent and control cervical cancer including guaranteed monitoring and appropriate follow-up for abnormal results. © World Health Organization 2015. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.

Vertical hepatitis C virus transmission: Main questions and answers

PubMed Central

Tosone, Grazia; Maraolo, Alberto Enrico; Mascolo, Silvia; Palmiero, Giulia; Tambaro, Orsola; Orlando, Raffaele

2014-01-01

Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents. PMID:25232447

Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

PubMed Central

Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

2015-01-01

Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

Effect of severity of steatosis as assessed ultrasonographically on hepatic vascular indices in non-alcoholic fatty liver disease.

PubMed

Mohammadi, Afshin; Ghasemi-rad, Mohammad; Zahedi, Hengameh; Toldi, Gergely; Alinia, Tahereh

2011-09-01

Early monitoring of non-alcoholic fatty liver disease (NAFLD) progression in obese patients is important to avoid the development of complications associated with fatty infiltration. of this study was to investigate the relationship between the degrees of fatty infiltration and reduced vascular compliance in NAFLD patients in the three main hepatic vessels. Two hundred and fourty subjects were enrolled in the study. They were divided into 4 groups: 60 controls, 60 grade 1 NAFLD patients, 60 grade 2 NAFLD patients and 60 grade 3 NAFLD patients. After US confirmation of the presence and grade of NAFLD, the peak and mean portal vein velocity (PPVV and MPVV, respectively), the hepatic artery resistance index (HARI), and the phasicity of the hepatic vein were measured. The PPVV was 19.6 +/- 2.4 cm/sec in patients with grade 1 fatty liver, 17.6 +/- 1.2 cm/sec in grade 2 and 15.4 +/- 1.1 cm/sec in grade 3. The MPVV was 16.6 +/- 2.4 cm/sec in patients with grade 1 fatty liver, 16.6 +/- 2.9 cm/sec in grade 2 and 12.7 +/- 0.7 cm/sec in grade 3. The HARI was 0.75 in patients with grade 1 fatty liver, 0.68 in grade 2 and 0.64 in grade 3. There was an inverse relationship between PPVV, MPVV and HARI and different grades of fatty liver in patients (p = 0.001 for PPVV (Figure 7) and HARI, p = 0.006 for MPVV. The values of the investigated liver blood flow parameters were inversely correlated with the fatty infiltration grading. Fatty infiltration can severely influence hepatic blood flow, pointing attention to the importance of early diagnosis and the need for hepatic vessel flow abnormalities characterization in the NAFLD population.

The effects of copper on blood and biochemical parameters of rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Dethloff, G.M.; Schlenk, D.; Khan, S.; Bailey, H.C.

1999-01-01

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 ??g Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 ??g Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 ??g Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and thestabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 ??g/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring.

Evaluation of Mir-224, Mir-215 and Mir-143 as Serum Biomarkers for HCV Associated Hepatocellular Carcinoma

PubMed

Mamdouh, Samah; Khorshed, Fatma; Aboushousha, Tarek; Hamdy, Hussam; Diab, Ayman; Seleem, Mohamed; Saber, Mohamed

2017-11-26

HCV induced hepatitis and hepatocellular carcinoma as its sequel are major health problems world-wide and especially in Egypt. For diagnosis and during treatment of liver diseases, liver functions are monitored through determination of serum levels of liver enzymes and α-fetoprotein although the obtained information is generally not sufficient for either early detection of hepatic insult or effective follow up of therapeutic effects. More sensitive biomarkers may help to achieve these goals. MiRNAs are small non-coding RNAs that have an important role in gene expression and regulation. Many, such as miR-224, miR-215, miR-143 are correlated with tumor appearance and with the degree of fibrosis in lung, breast and colon cancer. This study was performed to estimate the level of these miRNAs in serum of patients with HCV-associated hepatitis and HCC in relation to grade of hepatitis, stage of fibrosis and differentiation of tumor tissue. In addition, correlations between serological and tissue levels were assessed. A total of 80 patients were examined, out of which 50 were included in the study. Blood samples and tissue specimens from malignant tumor and corresponding non-tumor tissue of HCV hepatitis patients were collected. Blood samples from 20 healthy volunteers were also obtained as controls. It was found that miRNAs profiles differed in HCC patients compared to controls and HCV-associated hepatitis cases. Distinction of tumor grade and fibrosis stage of patients as well as between different grades of tumor differentiation proved possible, making miRNAs promising biomarkers for diagnosis and assessment of treatment response of HCC patients. Creative Commons Attribution License

Method and apparatus for simultaneously measuring temperature and pressure

DOEpatents

Hirschfeld, Tomas B.; Haugen, Gilbert R.

1988-01-01

Method and apparatus are provided for simultaneously measuring temperature and pressure in a class of crystalline materials having anisotropic thermal coefficients and having a coefficient of linear compression along the crystalline c-axis substantially the same as those perpendicular thereto. Temperature is determined by monitoring the fluorescence half life of a probe of such crystalline material, e.g., ruby. Pressure is determined by monitoring at least one other fluorescent property of the probe that depends on pressure and/or temperature, e.g., absolute fluorescent intensity or frequency shifts of fluorescent emission lines.

Identification of Hepatoprotective Constituents in Limonium tetragonum and Development of Simultaneous Analysis Method using High-performance Liquid Chromatography

PubMed Central

Lee, Jae Sun; Kim, Yun Na; Kim, Na-Hyun; Heo, Jeong-Doo; Yang, Min Hye; Rho, Jung-Rae; Jeong, Eun Ju

2017-01-01

Background: Limonium tetragonum, a naturally salt-tolerant halophyte, has been studied recently and is of much interest to researchers due to its potent antioxidant and hepatoprotective activities. Objective: In the present study, we attempted to elucidate bioactive compounds from ethyl acetate (EtOAc) soluble fraction of L. tetragonum extract. Furthermore, the simultaneous analysis method of bioactive EtOAc fraction of L. tetragonum has been developed using high-performance liquid chromatography (HPLC). Materials and Methods: Thirteen compounds have been successfully isolated from EtOAc fraction of L. tetragonum, and the structures of 1–13 were elucidated by extensive one-dimensional and two-dimensional spectroscopic methods including 1H-NMR, 13C-NMR, 1H-1H COSY, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser effect spectroscopy. Hepatoprotection of the isolated compounds against liver fibrosis was evaluated by measuring inhibition on hepatic stellate cells (HSCs) undergoing proliferation. Results: Compounds 1–13 were identified as gallincin (1), apigenin-3-O-β-D-galactopyranoside (2), quercetin (3), quercetin-3-O-β-D-galactopyranoside (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-gallate (6), (−)-epigallocatechin-3-(3″-O-methyl) gallate (7), myricetin-3-O-β-D-galactopyranoside (8), myricetin-3-O-(6″-O-galloyl)-β-D-galactopyranoside (9), myricetin-3-O-α-L-rhamnopyranoside (10), myricetin-3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (11), myricetin-3-O-(3″-O-galloyl)-α-L-rhamnopyranoside (12), and myricetin-3-O-α-L-arabinopyranoside (13), respectively. All compounds except for 4, 8, and 10 are reported for the first time from this plant. Conclusion: Myricetin glycosides which possess galloyl substituent (9, 11, and 12) showed most potent inhibitory effects on the proliferation of HSCs. SUMMARY In the present study, we have successfully isolated 13 compounds from bioactive fraction of Limonium tetragonum. The structures of compounds isolated have been fully elucidated, and hepatoprotective activities of compounds against liver fibrosis were evaluated by measuring inhibition on hepatic stellate cells undergoing proliferation. Furthermore, the simultaneous analysis method of bioactive ethyl acetate fraction of L. tetragonum has been developed using HPLC. Ten compounds identified herein are reported for the first time from this plant. Abbreviations used: HSQC: Heteronuclear single quantum coherence; HMBC: Heteronuclear multiple bond correlation; NOESY: Nuclear Overhauser effect spectroscopy; EGCG: Epigallocatechin-3-gallate; EGC: Epigallocatechin; HSC: Hepatic stellate cell; MTT: 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide. PMID:29200710

Simultaneous probing of bulk liquid phase and catalytic gas-liquid-solid interface under working conditions using attenuated total reflection infrared spectroscopy

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

Meemken, Fabian; Müller, Philipp; Hungerbühler, Konrad

Design and performance of a reactor set-up for attenuated total reflection infrared (ATR-IR) spectroscopy suitable for simultaneous reaction monitoring of bulk liquid and catalytic solid-liquid-gas interfaces under working conditions are presented. As advancement of in situ spectroscopy an operando methodology for gas-liquid-solid reaction monitoring was developed that simultaneously combines catalytic activity and molecular level detection at the catalytically active site of the same sample. Semi-batch reactor conditions are achieved with the analytical set-up by implementing the ATR-IR flow-through cell in a recycle reactor system and integrating a specifically designed gas feeding system coupled with a bubble trap. By the usemore » of only one spectrometer the design of the new ATR-IR reactor cell allows for simultaneous detection of the bulk liquid and the catalytic interface during the working reaction. Holding two internal reflection elements (IRE) the sample compartments of the horizontally movable cell are consecutively flushed with reaction solution and pneumatically actuated, rapid switching of the cell (<1 s) enables to quasi simultaneously follow the heterogeneously catalysed reaction at the catalytic interface on a catalyst-coated IRE and in the bulk liquid on a blank IRE. For a complex heterogeneous reaction, the asymmetric hydrogenation of 2,2,2-trifluoroacetophenone on chirally modified Pt catalyst the elucidation of catalytic activity/enantioselectivity coupled with simultaneous monitoring of the catalytic solid-liquid-gas interface is shown. Both catalytic activity and enantioselectivity are strongly dependent on the experimental conditions. The opportunity to gain improved understanding by coupling measurements of catalytic performance and spectroscopic detection is presented. In addition, the applicability of modulation excitation spectroscopy and phase-sensitive detection are demonstrated.« less

Dual-Color Fluorescence Imaging to Monitor CYP3A4 and CYP3A7 Expression in Human Hepatic Carcinoma HepG2 and HepaRG Cells

PubMed Central

Kubiura, Musashi; Hayashi, Ayaka; Ohbayashi, Tetsuya; Kazuki, Yasuhiro; Chesné, Christophe; Oshimura, Mitsuo; Tada, Masako

2014-01-01

Human adult hepatocytes expressing CYP3A4, a major cytochrome P450 enzyme, are required for cell-based assays to evaluate the potential risk of drug-drug interactions caused by transcriptional induction of P450 enzymes in early-phase drug discovery and development. However, CYP3A7 is preferentially expressed in premature hepatoblasts and major hepatic carcinoma cell lines. The human hepatocellular carcinoma cell line HepaRG possesses a high self-renewal capacity and can differentiate into hepatic cells similar to human adult hepatocytes in vitro. Transgenic HepaRG cells, in which the expression of fluorescent reporters is regulated by 35 kb regulatory elements of CYP3A4, have a distinct advantage over human hepatocytes isolated by collagenase perfusion, which are unstable in culture. Thus, we created transgenic HepaRG and HepG2 cells by replacing the protein-coding regions of human CYP3A4 and CYP3A7 with enhanced green fluorescent protein (EGFP) and DsRed reporters, respectively, in a bacterial artificial chromosome vector that included whole regulatory elements. The intensity of DsRed fluorescence was initially high during the proliferation of transgenic HepaRG cells. However, most EGFP-positive cells were derived from those in which DsRed fluorescence was extinguished. Comparative analyses in these transgenic clones showed that changes in the total fluorescence intensity of EGFP reflected fold changes in the mRNA level of endogenous CYP3A4. Moreover, CYP3A4 induction was monitored by the increase in EGFP fluorescence. Thus, this assay provides a real-time evaluation system for quality assurance of hepatic differentiation into CYP3A4-expressing cells, unfavourable CYP3A4 induction, and fluorescence-activated cell sorting-mediated enrichment of CYP3A4-expressing hepatocytes based on the total fluorescence intensities of fluorescent reporters, without the need for many time-consuming steps. PMID:25101946

Dual-color fluorescence imaging to monitor CYP3A4 and CYP3A7 expression in human hepatic carcinoma HepG2 and HepaRG cells.

PubMed

Tsuji, Saori; Kawamura, Fumihiko; Kubiura, Musashi; Hayashi, Ayaka; Ohbayashi, Tetsuya; Kazuki, Yasuhiro; Chesné, Christophe; Oshimura, Mitsuo; Tada, Masako

2014-01-01

Human adult hepatocytes expressing CYP3A4, a major cytochrome P450 enzyme, are required for cell-based assays to evaluate the potential risk of drug-drug interactions caused by transcriptional induction of P450 enzymes in early-phase drug discovery and development. However, CYP3A7 is preferentially expressed in premature hepatoblasts and major hepatic carcinoma cell lines. The human hepatocellular carcinoma cell line HepaRG possesses a high self-renewal capacity and can differentiate into hepatic cells similar to human adult hepatocytes in vitro. Transgenic HepaRG cells, in which the expression of fluorescent reporters is regulated by 35 kb regulatory elements of CYP3A4, have a distinct advantage over human hepatocytes isolated by collagenase perfusion, which are unstable in culture. Thus, we created transgenic HepaRG and HepG2 cells by replacing the protein-coding regions of human CYP3A4 and CYP3A7 with enhanced green fluorescent protein (EGFP) and DsRed reporters, respectively, in a bacterial artificial chromosome vector that included whole regulatory elements. The intensity of DsRed fluorescence was initially high during the proliferation of transgenic HepaRG cells. However, most EGFP-positive cells were derived from those in which DsRed fluorescence was extinguished. Comparative analyses in these transgenic clones showed that changes in the total fluorescence intensity of EGFP reflected fold changes in the mRNA level of endogenous CYP3A4. Moreover, CYP3A4 induction was monitored by the increase in EGFP fluorescence. Thus, this assay provides a real-time evaluation system for quality assurance of hepatic differentiation into CYP3A4-expressing cells, unfavourable CYP3A4 induction, and fluorescence-activated cell sorting-mediated enrichment of CYP3A4-expressing hepatocytes based on the total fluorescence intensities of fluorescent reporters, without the need for many time-consuming steps.

Comparative study of six sequential spectrophotometric methods for quantification and separation of ribavirin, sofosbuvir and daclatasvir: An application on Laboratory prepared mixture, pharmaceutical preparations, spiked human urine, spiked human plasma, and dissolution test.

PubMed

Hassan, Wafaa S; Elmasry, Manal S; Elsayed, Heba M; Zidan, Dalia W

2018-09-05

In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7 nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8 nm, and mean centering of the ratio spectra (MCR) at 224 nm and 258 nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) μg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05. Copyright © 2018 Elsevier B.V. All rights reserved.

Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

PubMed

Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

2013-06-01

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (p<0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p<0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p<0.05). A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy

PubMed Central

Guimarães, Juliana Rodrigues; Melgaço, Juliana Gil; Kevorkian, Yohan Britto; Bottino, Fernanda de Oliveira; Vieira, Yasmine Rangel; da Silva, Aline Campos de Azevedo; Pinto, Douglas Pereira; da Fonseca, Laís Bastos; Vilhena, Leandro Schiavo; Uiechi, Edilson; da Silva, Maria Cristina Carlan; Moran, Julio; Marchevsky, Renato Sérgio; Cruz, Oswaldo Gonçalves; Otonel, Rodrigo Alejandro Arellano; Alfieri, Amauri Alcindo; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pinto, Marcelo Alves

2017-01-01

Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment. PMID:28328941

Lasting immune memory against hepatitis B in 12-13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy.

PubMed

Behre, Ulrich; Van Der Meeren, Olivier; Crasta, Priya; Hanssens, Linda; Mesaros, Narcisa

2016-11-01

Vaccinating infants against hepatitis B virus (HBV) is the most effective way of preventing the disease. However, since HBV exposure can increase during adolescence, it is essential that antibody persistence is maintained. We evaluated the antibody persistence and immune memory against hepatitis B, in 12-13 y olds who had received complete primary + booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b (DTPa-HBV-IPV/Hib) vaccine in infancy. Open phase-IV study conducted at 12 centers in Germany [NCT02052661]. Adolescents aged 12-13 y, vaccinated with 4 doses of DTPa-HBV-IPV/Hib (Infanrix hexa™, GSK Vaccines) in infancy, received a single challenge dose of monovalent pediatric hepatitis B vaccine (Engerix™-B Kinder; GSK Vaccines). Blood samples were taken before and 1-month post-challenge to measure anti-hepatitis B (anti-HBs) antibodies using a chemiluminescence immunoassay (seroprotection cut-off: ≥10 mIU/ml). Post-challenge adverse events (AEs) were monitored. 300 subjects were vaccinated; of 293 subjects in the ATP immunogenicity cohort, 60.5% had pre-challenge anti-HBs antibodies ≥10 mIU/ml, which rose to 97.6% post-challenge (≥100 mIU/ml in 94.1%). An anamnestic response was seen in 96.5% subjects. A 150-fold increase in antibody geometric mean concentrations was observed (22.4 to 3502.6 mIU/ml). Pain (44%) and fatigue (24.3%) were the most frequent solicited local and general AEs, respectively; 14.7% subjects reported unsolicited symptoms during the 31-day post-vaccination period. Two vaccine-unrelated serious AEs occurred. Vaccination with DTPa-HBV-IPV/Hib in infancy induces sustained seroprotection and immune memory against HBV, as shown by the strong anamnestic response to the hepatitis B vaccine challenge in 12-13 year-old adolescents.

Simultaneous monitoring the real and imaginary parts of the analyte refractive index using liquid-core photonic bandgap Bragg fibers.

PubMed

Li, Jingwen; Qu, Hang; Skorobogatiy, Maksim

2015-09-07

We demonstrate simultaneous monitoring of the real and imaginary parts of the liquid analyte refractive index by using a hollow-core Bragg fiber. We apply this two-channel fiber sensor to monitor concentrations of various commercial cooling oils. The sensor operates using spectral monitoring of the fiber bandgap center wavelength, as well as monitoring of the fiber transmission amplitude at mid-bandgap position. The sensitivity of the fiber sensor to changes in the real part of the core refractive index is found to be 1460nm/Refractive index unit (RIU). By using spectral modality and effective medium theory, we determine the concentrations of the two commercial fluids from the measured refractive indices with an accuracy of ~0.57% for both low- and high-loss oils. Moreover, using an amplitude-based detection modality allows determination of the oil concentration with accuracy of ~1.64% for low-loss oils and ~2.81% for the high-loss oils.

Simultaneous trilateral communication based on three mutually coupled chaotic semiconductor lasers with optical feedback.

PubMed

Li, Qiliang; Lu, Shanshan; Bao, Qi; Chen, Dewang; Hu, Miao; Zeng, Ran; Yang, Guowei; Li, Shuqin

2018-01-10

In this paper, we propose a chaos-based scheme allowing for trilateral communication among three mutually coupled chaotic semiconductor lasers. The coupling through a partially transparent optical mirror between two lasers induces the chaotic dynamics. We numerically solve the delay rate equations of three lasers and demonstrate that the dynamics is completely synchronous. Herein, each laser is not only a transmitter but a receiver; three different messages are encoded by simultaneously modulating bias current of the three lasers. By monitoring the synchronization error between transmitter and receiver, and comparing the error with the message of the local laser, we can decipher the message of the sender. The investigation indicates that these messages introduced on the two ends of each link among three lasers can be simultaneously transmitted and restored, so the system can realize simultaneous trilateral communication. In this scheme, an eavesdropper can monitor the synchronization error, but one has no way to obtain the bits that are being sent, so the trilateral communication is secure.

Novel Interventional Management of Hepatic Hydatid Cyst with Nanosecond Pulses on Experimental Mouse Model.

PubMed

Chen, Xinhua; Zhang, Ruiqing; Aji, Tuerganaili; Shao, Yingmei; Chen, Yonggang; Wen, Hao

2017-07-03

The nanosecond pulsed electric field (nsPEF) is investigated as an alternative plan for benign hepatic hydatid cyst. Altogether 72 C57B6 mice were included. Normal group (n = 12) had no parasite injection and the other 60 mice were used to induce hydatid cyst in liver by injecting protoscolices in portal vein. The liver hydatid cysts were exposed to nsPEF with different doses and then follow up. The standard surgery was performed as positive control. The hydatid cyst growth was monitored by ultrasound; the morphology was checked by gross anatomy and pathology was tested by H&E stain. In nsPEF-treated groups no hepatic failure nor bleeding were observed. As a comparison, in the surgery group, high post-treatment complications occurred (50%). Significant parasite growth inhibition was seen in high nsPEF dose group as compared with control group (P < 0.05). Pathological analysis confirmed destruction of hydatid cyst with sharp demarcation defined by the electrodes. Laboratory analysis showed nsPEF stimulated a time-dependent infection and recoverable liver function. The traumatic reactions defined by white blood count was significant lower than surgery groups (P < 0.05).Preliminary studies demonstrate nsPEF ablation can be applied on hepatic hydatid by inhibiting parasite growth, destructing the cyst and stimulating infections.

Treatment of penetrating hepatic injuries: a retrospective analysis of 50 patients.

PubMed

Gonullu, D; Koksoy, F N; Ilgun, S; Demiray, O; Yucel, O; Yucel, T

2009-01-01

The aim of this study was to determine the possibility of non-operative treatment via retrospective analysis of our patients. Fifty patients with penetrating hepatic injuries were examined retrospectively with respect to trauma scores, associated injuries, complications, and mortality parameters. Thirteen injuries were caused by firearms, whereas 37 injuries were caused by stab wounds. Forty-three patients (86%) underwent laparotomy and 7 patients (14%) were monitored by CT and clinical findings (nonoperative group, NO group). The laparotomies were evaluated as non-therapeutic in 11 patients (22%) (NTL group) and therapeutic in 32 patients (64%) (TL group). The morbidity and mortality rates were 40 and 10%, respectively. RTS and ISS scores of the nonsurviving and the surviving patients were significantly different. The rates of major venous, grade IV-V hepatic injuries, and gunshot wounds were significantly higher in the nonsurviving patients when compared to the surviving patients. Major venous and grade IV-V hepatic injuries were the primary factors determining mortality and these injuries generally occurred as a result of firearm injuries. NTL occurring at a rate of 22% would decrease to 2% if 'RTS <7' criteria was added to the hemodynamic instability and/or peritoneal irritation findings determining surgical candidacy. Copyright 2009 S. Karger AG, Basel.

Listeriosis downregulates hepatic cytochrome P450 enzymes in sublethal murine infection.

PubMed

Kummer, Anne; Nishanth, Gopala; Koschel, Josephin; Klawonn, Frank; Schlüter, Dirk; Jänsch, Lothar

2016-10-01

Listeria monocytogenes (Lm) can cross the intestinal barrier in humans and then disseminates into different organs. Invasion of the liver occurs even in sublethal infections, however, knowledge of affected physiological processes is scarce. This study employed a sublethal murine infection model to investigate liver responses systematically by proteomics. Liver samples from three stages of the sublethal infection covering the initial invasion, the peak of infection, and the clearance phase (1, 3, 9 days postinoculation) were analyzed in comparison to samples from noninfected mice. Apart from flow cytometry and RT-PCRs for immune status control, liver responses were analyzed by quantitative peptide sequencing (HPLC-Orbitrap Fusion) using 4-plex iTRAQ-labeling. Accurate MS characterized about 3600 proteins and statistics revealed 15% of the hepatic proteome as regulated. Immunological data as well as protein regulation dynamics strongly indicate stage-specific hepatic responses in sublethal infections. Most notably, this study detected a comprehensive deregulation of drug metabolizing enzymes at all stages, including 25 components of the cytochrome P450 system. Sublethal Lm infection deregulates hepatic drug metabolizing pathways. This finding indicates the need to monitor drug administration along Lm infections, especially in all patients needing constant medication. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

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

2010-01-01

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

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

PubMed Central

May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

2011-01-01

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

Impact of hepatitis C oral therapy in portal hypertension.

PubMed

Libânio, Diogo; Marinho, Rui Tato

2017-07-14

Chronic hepatitis C is a leading cause of morbidity and mortality, mainly related to fibrosis/cirrhosis and portal hypertension. Direct antiviral agents are highly effective and safe and can now cure > 90% of the patients. Sustained viral response (SVR) after interferon-based regimens has been associated with improvement in liver function, fibrosis and portal hypertension in a significant proportion of patients, although a point of no return seems to exist from which viral elimination is no longer capable of preventing portal hypertension progression and liver decompensation. Indeed, although SVR is associated with improvement of hepatic venous pressure gradients and therefore a decreased risk of de novo esophageal varices, several studies show that viral clearance does not eliminate the risk of variceal progression, liver decompensation and death in patients with pre-established portal hypertension. Although evidence about the effects of direct antiviral agents (DAAs) on clinically significant outcomes is still scarce and with short follow-up, DAAs can decrease the burden of the disease if patients are timely treated before significant fibrosis and portal hypertension develops. Studies with longer follow-up are waited to establish the real magnitude of hepatitis C treatment on portal hypertension. Future studies should also focus on predictors of portal hypertension resolution since it can influence management and avoid unnecessary monitoring.

Hepatic and peripheral glucose metabolism in intensive care patients receiving continuous high- or low-carbohydrate enteral nutrition.

PubMed

Tappy, L; Berger, M; Schwarz, J M; McCamish, M; Revelly, J P; Schneiter, P; Jéquier, E; Chioléro, R

1999-01-01

The suppression of endogenous glucose production during parenteral nutrition is impaired in critically ill patients. It is, however, unknown whether enteral administration of carbohydrates, which normally promote hepatic glucose uptake, improves hepatic glucose metabolism in such patients. We studied two groups of 7 patients during a 3-day continuous isocaloric enteral nutrition. A high-carbohydrate, low-lipid (EN-C) or a high-lipid, low-carbohydrate (EN-L) nutrient mixture was administered. Endogenous glucose production assessed with [2H7]glucose was similarly increased in both groups, indicating absence of its suppression by carbohydrate feeding. Gluconeogenesis estimated from [13C]glucose synthesis during [13C]bicarbonate infusion also was not suppressed by EN-C compared with EN-L. Systemic appearance of exogenous glucose was monitored by enteral infusion of [6,6-2H]glucose and was not different from the rate of glucose equivalent administered enterally, indicating no significant hepatic uptake of glucose in both groups. Plasma glucose and insulin concentrations were slightly higher with EN-C, although not significantly, and plasma triglycerides were similar in both groups. Both nutrition formulas were well tolerated clinically. These results indicate that enteral carbohydrate administration, whatever its quantity, fails to suppress endogenous glucose production and to promote net splanchnic glucose uptake in critically ill patients.

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver.

PubMed

Su, Yan; Cailotto, Cathy; Foppen, Ewout; Jansen, Remi; Zhang, Zhi; Buijs, Ruud; Fliers, Eric; Kalsbeek, Andries

2016-02-15

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to distribute rhythmic information to the periphery via neural, humoral and/or behavioral connections. Until now, feeding, corticosterone and neural inputs are considered important signals for synchronizing daily rhythms in the liver. In this study, we investigated the necessity of neural inputs as well as of the feeding and adrenal hormone rhythms for maintaining daily hepatic clock gene rhythms. Clock genes kept their daily rhythm when only one of these three signals was disrupted, or when we disrupted hepatic neuronal inputs together with the adrenal hormone rhythm or with the daily feeding rhythm. However, all clock genes studied lost their daily expression rhythm after simultaneous disruption of the feeding and adrenal hormone rhythm. These data indicate that either a daily rhythm of feeding or adrenal hormones should be present to synchronize clock gene rhythms in the liver with the SCN. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Polarized release of hepatic microRNAs into bile and serum in response to cellular injury and impaired liver function.

PubMed

Verhoeven, Cornelia J; Farid, Waqar R R; Roest, Henk P; Ramakrishnaiah, Vedashree; de Ruiter, Petra E; de Jonge, Jeroen; Kwekkeboom, Jaap; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Ijzermans, Jan N M; van der Laan, Luc J W

2016-06-01

Extracellular microRNAs (miRNAs) in serum and bile are currently under intense investigation for biomarker purposes in liver disease. However, the directions and pathways by which miRNAs are released from hepatic cells remains largely unknown. Here, we investigated the release of hepatocyte and cholangiocyte-derived miRNAs (HDmiRs and CDmiRs) into blood and bile during various (patho)physiological hepatic conditions. MiRNA release was analysed using longitudinally collected tissue and paired bile and serum samples (n = 124) that were obtained from liver transplant recipients during follow-up. Cell-type specificity of HDmiRs and CDmiRs was confirmed in liver and common bile duct biopsies (P < 0.001). Analysis of paired bile and serum samples showed up to 20-times higher miRNA-levels in bile compared to serum (P < 0.0001). Fractionation of bile showed the majority of miRNAs being present in the unpelletable supernatant, where protein conjunctions protect miRNAs against degradation (P < 0.0001). During episodes of liver injury and histologically proven rejection in liver transplant recipients, relative HDmiR-levels in bile decreased while its levels in serum increased (P ≤ 0.015). Simultaneously, relative CDmiR-levels in bile significantly increased, while their levels in serum decreased. Related to liver excretory function, a strong positive correlation was observed between HDmiR-122 levels and bilirubin excretion into bile (R = 0.694, P < 0.0001), whereas CDmiRs showed an inverse correlation (P < 0.05). During impaired excretory function and injury, the liver shows polarized release of extracellular HDmiRs and CDmiRs. This sheds new light on the biology of hepatic miRNA release which is relevant for the interpretation of hepatic miRNAs as biomarkers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence and presentation of hepatitis B and C virus (HBV and HCV) infection in Vietnamese Americans via serial community serologic testing.

PubMed

Nguyen, Kelvin; Van Nguyen, Thai; Shen, Duke; Xia, Victor; Tran, Diep; Banh, Khanh; Ruan, Victor; Hu, Ke-Qin

2015-02-01

The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.

Pure laparoscopic right hepatectomy for giant hemangioma using anterior approach.

PubMed

Kim, Seok-Hwan; Kim, Ki-Hun; Kirchner, Varvara A; Lee, Sang-Kyung

2017-05-01

Laparoscopic major hepatectomy remains a challenging procedure [1, 2]. In the case of giant tumors in the right liver, conventional approach (complete mobilization of the right liver before parenchymal transection) could be dangerous during mobilization because of large volume and weight [3, 4]. We present the case of a pure laparoscopic right hepatectomy for a giant hemangioma using an anterior approach. We achieved the informed consent with this patient and approved by the Ethics Committee of the Asan Medical Center. Giant hemangioma (13 × 11 × 14 cm) was located in right liver. After glissonean approach [5], Pringle maneuver was performed during the hepatic parenchymal transection. For the transection, the Cavitron Ultrasonic Surgical Aspirator was used. Small hepatic vein branches along the middle hepatic vein and small glissonean pedicles were sealed and divided with a THUNDERBEATTM (Olympus), which is the device with integration of both bipolar and ultrasonic energies delivered simultaneously. iDriveTM Ultra Powered Stapling device (Medtronic) was used for division of right glissonean pedicle and large hepatic veins. Hemangioma was removed through the lower abdominal transverse incision using the endo-bag. This technique has the advantage of avoiding excessive bleeding caused by avulsion of the hepatic vein and caval branches, iatrogenic tumor rupture [3]. By means of the anterior approach, pure laparoscopic right hepatectomy was performed successfully without intraoperative complications and transfusions. The operation time was 202 min, and the estimated blood loss was less than 150 ml. On postoperative day 3, computed tomographic scan showed no pathological findings. The patient was discharged on postoperative day 5 without complications. Laparoscopic approach has good results because of the view with magnification enabling meticulous hemostasis and the small wounds that give patients less pain [6, 7]. The authors recommend that the laparoscopic anterior approach is safe and feasible for right hepatectomy, even for giant tumors.

Display/control requirements for automated VTOL aircraft

NASA Technical Reports Server (NTRS)

Hoffman, W. C.; Kleinman, D. L.; Young, L. R.

1976-01-01

A systematic design methodology for pilot displays in advanced commercial VTOL aircraft was developed and refined. The analyst is provided with a step-by-step procedure for conducting conceptual display/control configurations evaluations for simultaneous monitoring and control pilot tasks. The approach consists of three phases: formulation of information requirements, configuration evaluation, and system selection. Both the monitoring and control performance models are based upon the optimal control model of the human operator. Extensions to the conventional optimal control model required in the display design methodology include explicit optimization of control/monitoring attention; simultaneous monitoring and control performance predictions; and indifference threshold effects. The methodology was applied to NASA's experimental CH-47 helicopter in support of the VALT program. The CH-47 application examined the system performance of six flight conditions. Four candidate configurations are suggested for evaluation in pilot-in-the-loop simulations and eventual flight tests.

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline

PubMed Central

2014-01-01

Background Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Methods Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Results Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. Conclusions These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the microglia activation and neurological decline associated with hepatic encephalopathy. Methods used to modulate CCL2 levels and/or reduce CCR2/CCR4 activity may be potential therapeutic targets for the management of hepatic encephalopathy due to acute liver injury. PMID:25012628

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

PubMed

McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

2014-07-10

Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the microglia activation and neurological decline associated with hepatic encephalopathy. Methods used to modulate CCL2 levels and/or reduce CCR2/CCR4 activity may be potential therapeutic targets for the management of hepatic encephalopathy due to acute liver injury.

Nonoperative management of blunt hepatic injury: an Eastern Association for the Surgery of Trauma practice management guideline.

PubMed

Stassen, Nicole A; Bhullar, Indermeet; Cheng, Julius D; Crandall, Marie; Friese, Randall; Guillamondegui, Oscar; Jawa, Randeep; Maung, Adrian; Rohs, Thomas J; Sangosanya, Ayodele; Schuster, Kevin; Seamon, Mark; Tchorz, Kathryn M; Zarzuar, Ben L; Kerwin, Andrew

2012-11-01

During the last century, the management of blunt force trauma to the liver has changed from observation and expectant management in the early part of the 1900s to mainly operative intervention, to the current practice of selective operative and nonoperative management. These issues were first addressed by the Eastern Association for the Surgery of Trauma in the Practice Management Guidelines for Nonoperative Management of Blunt Injury to the Liver and Spleen published online in 2003. Since that time, a large volume of literature on these topics has been published requiring a reevaluation of the previous Eastern Association for the Surgery of Trauma guideline. The National Library of Medicine and the National Institutes of Health MEDLINE database were searched using PubMed (http://www.pubmed.gov). The search was designed to identify English-language citations published after 1996 (the last year included in the previous guideline) using the keywords liver injury and blunt abdominal trauma. One hundred seventy-six articles were reviewed, of which 94 were used to create the current practice management guideline for the selective nonoperative management of blunt hepatic injury. Most original hepatic guidelines remained valid and were incorporated into the greatly expanded current guidelines as appropriate. Nonoperative management of blunt hepatic injuries currently is the treatment modality of choice in hemodynamically stable patients, irrespective of the grade of injury or patient age. Nonoperative management of blunt hepatic injuries should only be considered in an environment that provides capabilities for monitoring, serial clinical evaluations, and an operating room available for urgent laparotomy. Patients presenting with hemodynamic instability and peritonitis still warrant emergent operative intervention. Intravenous contrast enhanced computed tomographic scan is the diagnostic modality of choice for evaluating blunt hepatic injuries. Repeated imaging should be guided by a patient's clinical status. Adjunctive therapies like angiography, percutaneous drainage, endoscopy/endoscopic retrograde cholangiopancreatography and laparoscopy remain important adjuncts to nonoperative management of hepatic injuries. Despite the explosion of literature on this topic, many questions regarding nonoperative management of blunt hepatic injuries remain without conclusive answers in the literature.

Frequency of Acute Hepatitis Following Acute Paraphenylene Diamine Intoxication.

PubMed

Ishtiaq, Rizwan; Shafiq, Sadaf; Imran, Ali; Masroor Ali, Qazi; Khan, Raheel; Tariq, Hassan; Ishtiaq, Daniyal

2017-04-21

Paraphenylene diamine (PPD) ingestion is manifesting as one of the more common ways of committing suicide in Southern Punjab, Pakistan, especially Bahawalpur. PPD is an ingredient of a compound commonly known "Kala Pathar" which means "Black Stone" in Urdu. It is readily available in the market at low cost and is used to dye hair and fur. Its intoxication inhibits cellular oxidation and affects the muscles causing rhabdomyolysis. This leads to myoglobinuria followed by renal failure and edema of face and throat resulting in respiratory difficulty. Very little is known about the impact of PPD intoxication on liver tissue. The purpose of the study was to find out the frequency of acute hepatitis following PPD intoxication. We reviewed the medical records of 109 patients with PPD intoxication admitted to Medical Unit-2, Bahawalpur Victoria Hospital from January 1, 2015, to June 30, 2015, in a descriptive, cross-sectional study. We noted the frequency of acute hepatitis and other complications, and we recorded the demographic features, clinical features, and outcomes of these patients. Our study included 32 men (29%) and 77 women (71%). The mean age was 22 ± 3.4 years, and most patients were young women aged 15 to 24 years. Suicidal ingestion was the leading cause of admission for 101 patients (93%). The most common clinical presentation was cervicofacial edema (95%), throat pain (88%), dysphonia (95%), cola-colored urine (100%), and oliguria (95%). Rhabdomyolysis (86%), acute hepatitis (51%), and acute renal failure (63%) were the most common clinical conditions following poisoning. Overall mortality was noted in 39 patients (36%) while all other patients achieved complete clinical recovery (64%). In patients with mortality, 20 of 39 (51%) developed acute hepatitis. Most patients (95%) in our study underwent tracheostomy. The frequency of acute hepatitis in PPD intoxication is high in this population, especially in young women. Measures need to be instituted regarding the management of acute hepatitis in PPD intoxication to improve patient outcomes. Workups in patients with PPD poisoning should include regular monitoring of aspartate aminotransferase and alanine aminotransferase to observe any damages to the liver so that acute hepatitis can be managed in a timely fashion.

[Clinical value of ammonia determination in venous blood in chronic cor pulmonale].

PubMed

Szulc, E J; Sworzyńska, I

1978-01-01

The authors have examined 43 workers of the Warszawa works: 20 healthy persons and 23 with chronic pulmocardiac syndrome. An increased ammonia level in venous blood, above 48 gamma %, was found in those with chronic pulmocardiac syndrome with simultaneous circulatory insufficiency. Ammonia level in the blood of those with chronic pulmocardiac syndrome but without circulatory insufficiency was normal. These studies indicate that the increase of ammonia concentration in venous blood in chronic pulmocardiac syndrome results from disturbance in hepatic cell function, intensified during circulatory insufficiency.

Dynamic data filtering system and method

DOEpatents

Bickford, Randall L; Palnitkar, Rahul M

2014-04-29

A computer-implemented dynamic data filtering system and method for selectively choosing operating data of a monitored asset that modifies or expands a learned scope of an empirical model of normal operation of the monitored asset while simultaneously rejecting operating data of the monitored asset that is indicative of excessive degradation or impending failure of the monitored asset, and utilizing the selectively chosen data for adaptively recalibrating the empirical model to more accurately monitor asset aging changes or operating condition changes of the monitored asset.

Fully automated, internally controlled quantification of hepatitis B Virus DNA by real-time PCR by use of the MagNA Pure LC and LightCycler instruments.

PubMed

Leb, Victoria; Stöcher, Markus; Valentine-Thon, Elizabeth; Hölzl, Gabriele; Kessler, Harald; Stekel, Herbert; Berg, Jörg

2004-02-01

We report on the development of a fully automated real-time PCR assay for the quantitative detection of hepatitis B virus (HBV) DNA in plasma with EDTA (EDTA plasma). The MagNA Pure LC instrument was used for automated DNA purification and automated preparation of PCR mixtures. Real-time PCR was performed on the LightCycler instrument. An internal amplification control was devised as a PCR competitor and was introduced into the assay at the stage of DNA purification to permit monitoring for sample adequacy. The detection limit of the assay was found to be 200 HBV DNA copies/ml, with a linear dynamic range of 8 orders of magnitude. When samples from the European Union Quality Control Concerted Action HBV Proficiency Panel 1999 were examined, the results were found to be in acceptable agreement with the HBV DNA concentrations of the panel members. In a clinical laboratory evaluation of 123 EDTA plasma samples, a significant correlation was found with the results obtained by the Roche HBV Monitor test on the Cobas Amplicor analyzer within the dynamic range of that system. In conclusion, the newly developed assay has a markedly reduced hands-on time, permits monitoring for sample adequacy, and is suitable for the quantitative detection of HBV DNA in plasma in a routine clinical laboratory.

Multisensor Capacitance Probes for Simultaneously Monitoring Rice Field Soil-Water- Crop-Ambient Conditions.

PubMed

Brinkhoff, James; Hornbuckle, John; Dowling, Thomas

2017-12-26

Multisensor capacitance probes (MCPs) have traditionally been used for soil moisture monitoring and irrigation scheduling. This paper presents a new application of these probes, namely the simultaneous monitoring of ponded water level, soil moisture, and temperature profile, conditions which are particularly important for rice crops in temperate growing regions and for rice grown with prolonged periods of drying. WiFi-based loggers are used to concurrently collect the data from the MCPs and ultrasonic distance sensors (giving an independent reading of water depth). Models are fit to MCP water depth vs volumetric water content (VWC) characteristics from laboratory measurements, variability from probe-to-probe is assessed, and the methodology is verified using measurements from a rice field throughout a growing season. The root-mean-squared error of the water depth calculated from MCP VWC over the rice growing season was 6.6 mm. MCPs are used to simultaneously monitor ponded water depth, soil moisture content when ponded water is drained, and temperatures in root, water, crop and ambient zones. The insulation effect of ponded water against cold-temperature effects is demonstrated with low and high water levels. The developed approach offers advantages in gaining the full soil-plant-atmosphere continuum in a single robust sensor.

Simultaneous life extension and crack monitoring of fatigue-damaged steel members using multifunctional carbon nanotube based composites

NASA Astrophysics Data System (ADS)

Ahmed, Shafique; Schumacher, Thomas; Thostenson, Erik T.; McConnell, Jennifer

2017-04-01

Steel structures including bridges are susceptible to cracking, particularly due to fatigue-sensitive details found in older designs. Therefore, one of the major challenges to keep those steel bridges in service is to rehabilitate existing and potential fatigue damage. There are several conventional approaches to extend the fatigue-life of damaged steel members, e.g., drilling a crack stop-hole to reduce the stress concentration at the crack tip as well as welding and bolting of steel plates or adhesive-bonding of fiber-reinforced polymers (FRP) to reduce the overall stresses. Improvement in material properties of FRP and adhesives make them a viable candidate to apply for extending the fatigue-life of steel members. However, drawbacks include the potential for debonding of the adhesive layer and/or interfaces between adhesive and adherents as well as difficulty in monitoring fatigue crack growth after rehabilitation. In this research, a holistic approach is proposed and evaluated for simultaneous extension of fatigue-life and monitoring by integrating a carbon nanotube (CNT)-based sensing layer with an adhesively-bonded FRP reinforcement. CNT-based sensing layers have a nerve-like electric resistance network, which enables distributed sensing capabilities to monitor stress levels, crack growth, and damage progression. Using laboratory-scale experiments, the simultaneous fatigue-life extension and crack monitoring capability of multifunctional CNT-based composites was evaluated. This paper introduces the fundamental concept of integrated fatigue-rehabilitation and monitoring of steel members, presents a laboratory-scale experiment to demonstrate the feasibility and effectiveness, and discusses challenges for implementation in real structures.

Quantitative monitoring of two simultaneously binding species using Label-Enhanced surface plasmon resonance.

PubMed

Eng, Lars; Garcia, Brandon L; Geisbrecht, Brian V; Hanning, Anders

2018-02-26

Surface plasmon resonance (SPR) is a well-established method for biomolecular interaction studies. SPR monitors the binding of molecules to a solid surface, embodied as refractive index changes close to the surface. One limitation of conventional SPR is the universal nature of the detection that results in an inability to qualitatively discriminate between different binding species. Furthermore, it is impossible to directly discriminate two species simultaneously binding to different sites on a protein, which limits the utility of SPR, for example, in the study of allosteric binders or bi-specific molecules. It is also impossible in principle to discriminate protein conformation changes from actual binding events. Here we demonstrate how Label-Enhanced SPR can be utilized to discriminate and quantitatively monitor the simultaneous binding of two different species - one dye-labeled and one unlabeled - on a standard, single-wavelength SPR instrument. This new technique increases the versatility of SPR technology by opening up application areas where the usefulness of the approach has previously been limited. Copyright © 2018 Elsevier Inc. All rights reserved.

Titration of Alanine Monitored by NMR Spectroscopy: A Biochemistry Laboratory Experiment

ERIC Educational Resources Information Center

Waller, Francis J.; And Others

1977-01-01

The experiment described here involves simultaneous monitoring of pH and NMR chemical shifts during an aqueous titration of alpha- and beta-alanine. This experiment is designed for use in an undergraduate biochemistry course. (MR)

[Clinical evaluation of a novel HBsAg quantitative assay].

PubMed

Takagi, Kazumi; Tanaka, Yasuhito; Naganuma, Hatsue; Hiramatsu, Kumiko; Iida, Takayasu; Takasaka, Yoshimitsu; Mizokami, Masashi

2007-07-01

The clinical implication of the hepatitis B surface antigen (HBsAg) concentrations in HBV-infected individuals remains unclear. The aim of this study was to evaluate a novel fully automated Chemiluminescence Enzyme Immunoassay (Sysmex HBsAg quantitative assay) by comparative measurements of the reference serum samples versus two independent commercial assays (Lumipulse f or Architect HBsAg QT). Furthermore, clinical usefulness was assessed for monitoring of the serum HBsAg levels during antiviral therapy. A dilution test using 5 reference-serum samples showed linear correlation curve in range from 0.03 to 2,360 IU/ml. The HBsAg was measured in total of 400 serum samples and 99.8% had consistent results between Sysmex and Lumipulse f. Additionally, a positive linear correlation was observed between Sysmex and Architect. To compare the Architect and Sysmex, both methods were applied to quantify the HBsAg in serum samples with different HBV genotypes/subgenotypes, as well as in serum contained HBV vaccine escape mutants (126S, 145R). Correlation between the methods was observed in results for escape mutants and common genotypes (A, B, C) in Japan. Observed during lamivudine therapy, an increase in HBsAg and HBV DNA concentrations preceded the aminotransferase (ALT) elevation associated with drug-resistant HBV variant emergence (breakthrough hepatitis). In conclusion, reliability of the Sysmex HBsAg quantitative assay was confirmed for all HBV genetic variants common in Japan. Monitoring of serum HBsAg concentrations in addition to HBV DNA quantification, is helpful in evaluation of the response to lamivudine treatment and diagnosis of the breakthrough hepatitis.

Development of a real-time radon monitoring system for simultaneous measurements in multiple sites

NASA Astrophysics Data System (ADS)

Yamamoto, S.; Yamasoto, K.; Iida, T.

1999-12-01

A real-time radon monitoring system that can simultaneously measure radon concentrations in multiple sites was developed and tested. The system consists of maximum of four radon detectors, optical fiber cables and a data acquisition personal computer. The radon detector uses a plastic scintillation counter that collects radon daughters in the chamber electrostatically. The applied voltage on the photocathode for the photomultiplier tube (PMT) acts as an electrode for radon daughters. The thickness of the plastic scintillator was thin, 50 /spl mu/m, so as to minimize the background counts due to the environmental gamma rays or beta particles. The energy discriminated signals from the radon detectors are fed to the data acquisition personal computer via optical fiber cables. The system made it possible to measure the radon concentrations in multiple sites simultaneously.

Simultaneous Monitoring of Ballistocardiogram and Photoplethysmogram Using Camera

PubMed Central

Shao, Dangdang; Tsow, Francis; Liu, Chenbin; Yang, Yuting; Tao, Nongjian

2017-01-01

We present a noncontact method to measure Ballistocardiogram (BCG) and Photoplethysmogram (PPG) simultaneously using a single camera. The method tracks the motion of facial features to determine displacement BCG, and extracts the corresponding velocity and acceleration BCGs by taking first and second temporal derivatives from the displacement BCG, respectively. The measured BCG waveforms are consistent with those reported in literature and also with those recorded with an accelerometer-based reference method. The method also tracks PPG based on the reflected light from the same facial region, which makes it possible to track both BCG and PPG with the same optics. We verify the robustness and reproducibility of the noncontact method with a small pilot study with 23 subjects. The presented method is the first demonstration of simultaneous BCG and PPG monitoring without wearing any extra equipment or marker by the subject. PMID:27362754

1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

PubMed

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid; Ohrt, Johanne Dam; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-01-01

This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years. In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

Hemagglutinating virus of Japan-artificial viral envelope liposome-mediated cotransfer of bag-1 and bcl-2 genes protects hepatic cells against ischemic injury through BAG-1-assisted preferential enhancement of bcl-2 protein expression.

PubMed

Yanada, Shinobu; Sasaki, Masao; Takayama, Shinichi; Kaneda, Yasufumi; Miwa, Nobuhiko

2005-05-01

Hepatic injury subsequent to ischemia-reperfusion (I/R) was demonstrated in our previous study to be prevented by hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE) liposome-mediated gene transfer of the antiapoptotic gene, human bcl-2 (h-bcl-2). In the present study, we introduced simultaneously both mouse Bcl-2-associated athanogene 1 (m-bag-1) and the h-bcl-2 gene by the same HVJ-AVE liposome transfection method, and found that I/R-induced hepatic injuries such as release of hepatic marker enzymes into blood, cell morphological degeneration, and cellular DNA strand cleavage were suppressed more effectively than by transfection with either gene singly. In addition, the h-Bcl-2 expression level in the ischemic state, but not in the nonischemic state, was markedly higher in h-bcl-2/m-bag-1-cotransfected liver than in h-bcl-2-transfected liver. In contrast, the m-BAG-1 expression level in the ischemic state, but not in the nonischemic state, was only slightly higher in h-bcl-2/m-bag-1-cotransfected liver than in m-bag-1-transfected liver. Thus, with dual gene cotransfer, coexistent Bcl-2 protein exerts no activity to assist a marked enhancement of BAG-1 protein, whereas the function of overexpressed BAG-1 as a Bcl-2-binding protein may lead to the enhancement of efficient expression of h-Bcl-2 in I/R-treated liver as compared with nonischemic liver, which results in repression of diverse I/R-induced cell death symptoms, presumably through the formation of functional complexes of BAG-1 and Bcl-2.

Simultaneous chromatic dispersion monitoring and optical modulation format identification utilizing four wave mixing

NASA Astrophysics Data System (ADS)

Cui, Sheng; Qiu, Chen; Ke, Changjian; He, Sheng; Liu, Deming

2015-11-01

This paper presents a method which is able to monitor the chromatic dispersion (CD) and identify the modulation format (MF) of optical signals simultaneously. This method utilizes the features of the output curve of the highly sensitive all-optical CD monitor based on four wave mixing (FWM). From the symmetric center of the curve CD can be estimated blindly and independently, while from the profile and convergence region of the curve ten commonly used modulation formats can be recognized with simple algorithm based on maximum correlation classifier. This technique does not need any high speed optoelectronics and has no limitation on signal rate. Furthermore it can tolerate large CD distortions and is robust to polarization mode dispersion (PMD) and amplified spontaneous emission (ASE) noise.

Simultaneous long-term monitoring of LS I +61°303 by OVRO and Fermi-LAT

NASA Astrophysics Data System (ADS)

Jaron, Frédéric; Massi, Maria; Kiehlmann, Sebastian; Hovatta, Talvikki

2018-07-01

Previous long-term monitorings of the γ-ray-loud X-ray binary LS I +61°303 have revealed the presence of a long-term modulation of ˜4.5 yr. After 9 yr of simultaneous monitoring of LS I +61°303 by the Owens Valley Radio Observatory and the Fermi-LAT, two cycles of the long-term period are now available. Here we perform timing analysis on the radio and the γ-ray light curves. We confirm the presence of previously detected periodicities at both radio and GeV γ-ray wavelengths. Moreover, we discover an offset of the long-term modulation between radio and γ-ray data which could imply different locations of the radio (15 GHz) and GeV emission along the precessing jet.

SIMULTANEOUS B'V'R' MONITORING OF BL LACERTAE OBJECT S5 0716+714 AND DETECTION OF INTER-BAND TIME DELAY

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

Wu Jianghua; He Xiangtao; Boettcher, Markus

We present the results of our optical monitoring of the BL Lac object S5 0716+714 over seven nights in 2006 December. The monitoring was carried out simultaneously at three optical wavelengths with a novel photometric system. The object did not show large-amplitude internight variations during this period. Intranight variations were observed on four nights and probably on one more. Strong bluer-when-brighter chromatism was detected on both intranight and internight timescales. The intranight variation amplitude decreases in the wavelength sequence of B', R', and V'. Cross-correlation analyses revealed that the variability at the B' and V' bands leads that at themore » R' band by about 30 minutes on one night.« less

The transplantation donation process in the Centro de Investigaciones Medico Quirurgicas of Cuba: 1999-2002.

PubMed

Abdo, A; Ugarte, J C; Castellanos, R; González, L; López, O; Hernández, J C; Valdivia, J; Almora, E; Suárez, O; Diaz, J; Collera, S; Enamorado, A; Vázquez, A; Beníte, P; Dominguez, J; Wilford, M; Falcon, J

2003-08-01

In 1998 in the Centro de Investigaciones Medico Quirurgicas the Transplant Coordination Office (TCO) was created, with the aim to organize a system to support a hepatic transplantation program. This organization, which changed the transplantation-donation process not only in our center but in the whole country, is described in this article. The files of donors generated in our hospital were studied together with the transplant coordination records, from 1999 till the first half of 2002. In the period studied, 21 potential donors were diagnosed with brain death, yielding a donation rate of 71.4%. Brain death was most frequently caused by vascular brain disease; however, in the realized donor group, the cranioencephalic trauma predominated. The typical donor was a man of average age 39.2 years (range, 18-86 years). Among the potential donors, 24% were excluded based on medical criteria, and 5% due to family objections. Forty liver transplantation were performed in 36 patients including 1 liver-kidney simultaneous procedure. The principal etiologies for transplant included hepatitis C virus cirrhosis, 22%; alcoholic, 19%; and acute hepatic failure, 13%. Kidney transplantations were performed in 70 patients, including 41 from cadaveric donors (53.6%) and 29 from living related donors (41.4%). In 2001, a pancreas-kidney transplantation program was started. The creation of the TCO has been of paramount importance to optimize transplantation program functions.

cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.

PubMed

Myers, N C; Grune, S; Jameson, H L; Sawkat-Anwer, M

1996-03-01

The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.

The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH.

PubMed

Barbero-Becerra, Varenka J; Giraudi, Pablo J; Chávez-Tapia, Norberto C; Uribe, Misael; Tiribelli, Claudio; Rosso, Natalia

2015-10-01

A complex interplay exists between hepatocytes and hepatic stellate cells (HSC) in hepatic fibrogenesis. The activation of HSCs after liver injury leads to production of extracellular matrix (ECM). Co-culture models could be useful to mimic the liver microenvironment. This study evaluates the effect of free fatty acids (FFA) on HSC cells and the interplay with hepatocytes via both soluble-mediator and cell-cell contact. The human hepatocyte cell line (HuH7) and HSC cells (LX2) were exposed to FFA for 24 h in 3 different experimental set-ups: (A) monoculture of HSC; (B) Transwell® system (effect of soluble mediators); and (C) Simultaneous Co-Culture (SCC) (cell-to-cell connections). Intracellular FFA accumulation was assessed qualitatively (microscopy) and quantitatively (flow cytometry); the activation of HSC (alpha smooth muscle actin, α-SMA) expression of ECM components were quantified by RT-PCR. FFA exposure induces intracellular fat accumulation in all the experimental set-up but the expression of α-SMA was significantly increased only in SCC. On the contrary, the expression of ECM was substantially decreased in the transwell® system. The HSC activation is independent of FFA accumulation but requires cell-to-cell interaction with hepatocyte. On the contrary, the gene regulation of ECM components seems to occur through paracrine mediators. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Action of Antidiabetic Plants of the Canadian James Bay Cree Traditional Pharmacopeia on Key Enzymes of Hepatic Glucose Homeostasis

PubMed Central

Nachar, Abir; Vallerand, Diane; Musallam, Lina; Lavoie, Louis; Arnason, John; Haddad, Pierre S.

2013-01-01

We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada) to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase) and glycogen synthase (GS) activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines. PMID:23864882

Live Attenuated Vaccine Based on Duck Enteritis Virus against Duck Hepatitis A Virus Types 1 and 3

PubMed Central

Zou, Zhong; Ma, Ji; Huang, Kun; Chen, Huanchun; Liu, Ziduo; Jin, Meilin

2016-01-01

As causative agents of duck viral hepatitis, duck hepatitis A virus type 1 (DHAV-1) and type 3 (DHAV-3) causes significant economic losses in the duck industry. However, a licensed commercial vaccine that simultaneously controls both pathogens is currently unavailable. Here, we generated duck enteritis virus recombinants (rC-KCE-2VP1) containing both VP1 from DHAV-1 (VP1/DHAV-1) and VP1 from DHAV-3 (VP1/DHAV-3) between UL27 and UL26. A self-cleaving 2A-element of FMDV was inserted between the two different types of VP1, allowing production of both proteins from a single open reading frame. Immunofluorescence and Western blot analysis results demonstrated that both VP1 proteins were robustly expressed in rC-KCE-2VP1-infected chicken embryo fibroblasts. Ducks that received a single dose of rC-KCE-2VP1 showed potent humoral and cellular immune responses and were completely protected against challenges of both pathogenic DHAV-1 and DHAV-3 strains. The protection was rapid, achieved as early as 3 days after vaccination. Moreover, viral replication was fully blocked in vaccinated ducks as early as 1 week post-vaccination. These results demonstrated, for the first time, that recombinant rC-KCE-2VP1 is potential fast-acting vaccine against DHAV-1 and DHAV-3. PMID:27777571

Simultaneous and quantitative monitoring of co-cultured Pseudomonas aeruginosa and Staphylococcus aureus with antibiotics on a diffusometric platform

NASA Astrophysics Data System (ADS)

Chung, Chih-Yao; Wang, Jhih-Cheng; Chuang, Han-Sheng

2017-04-01

Successful treatments against bacterial infections depend on antimicrobial susceptibility testing (AST). However, conventional AST requires more than 24 h to obtain an outcome, thereby contributing to high patient mortality. An antibiotic therapy based on experiences is therefore necessary for saving lives and escalating the emergence of multidrug-resistant pathogens. Accordingly, a fast and effective drug screen is necessary for the appropriate administration of antibiotics. The mixed pathogenic nature of infectious diseases emphasizes the need to develop an assay system for polymicrobial infections. On this basis, we present a novel technique for simultaneous and quantitative monitoring of co-cultured microorganisms by coupling optical diffusometry with bead-based immunoassays. This simple integration simultaneously achieves a rapid AST analysis for two pathogens. Triple color particles were simultaneously recorded and subsequently analyzed by functionalizing different fluorescent color particles with dissimilar pathogen-specific antibodies. Results suggested that the effect of the antibiotic, gentamicin, on co-cultured Pseudomonas aeruginosa and Staphylococcus aureus was effectively distinguished by the proposed technique. This study revealed a multiplexed and time-saving (within 2 h) platform with a small sample volume (~0.5 μL) and a low initial bacterial count (50 CFU per droplet, ~105 CFU/mL) for continuously monitoring the growth of co-cultured microorganisms. This technique provides insights into timely therapies against polymicrobial diseases in the near future.

Investigation of hepatobiliary disposition of doxorubicin following intrahepatic delivery of different dosage forms.

PubMed

Lilienberg, Elsa; Ebeling Barbier, Charlotte; Nyman, Rickard; Hedeland, Mikael; Bondesson, Ulf; Axén, Niklas; Lennernäs, Hans

2014-01-06

Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.

Risk Assessment in Shellfish-Borne Outbreaks of Hepatitis A▿

PubMed Central

Pintó, Rosa M.; Costafreda, M. Isabel; Bosch, Albert

2009-01-01

In the present work, we aimed at determining the relationship between the hepatitis A virus (HAV) numbers in imported frozen coquina clams involved in two hepatitis outbreaks, as well as the risk for human health. Due to HAV unculturability, a standardized TaqMan real-time reverse transcription-PCR controlling the virus/nucleic acid extraction and enzyme efficiencies was employed to figure the exposure dose for clams responsible for hepatitis cases. HAV numbers were then employed to figure the risk of infection based on a dose-response model for echovirus 12. The estimated risk of infection after consumption of lightly cooked clams matched actual attack rates. Our data show that prospective monitoring of bivalve samples may fail to prevent the occurrence of outbreaks, since HAV was detected in 44% of samples directly associated with cases but was undetectable in samples that were randomly collected from the importers and belonged to the same batches. A correlation was nevertheless observed between the prevalence of hepatitis A cases in the harvesting areas and positive HAV isolation in clams, which points to the need to identify and prevent hazards rather than relying on random sampling of finished products to ensure safety. However, when evidence shows that a critical limit of viral contamination has been exceeded in the potential sources of contamination discharging into the shellfish-growing beds, quantitative virological analysis addressing quality assurance and quality control requirements should be performed with the bivalves. This work provides the first evidence of accurate HAV levels in shellfish involved in outbreaks that could be of use for risk assessment purposes. PMID:19820160

Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody.

PubMed

Mesenas, Steven J; Chow, Wan C; Zhao, Yi; Lim, Gek K; Oon, Chong J; Ng, Han S

2002-02-01

This study aims to examine the genomic variants of the 'a' epitope in chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Eighteen HBV carriers were studied. Hepatitis B virus (HBV) DNA was extracted and the 'a' epitope region was amplified and sequenced. Eighteen Chinese asymptomatic HBV carriers were studied. There were 13 patients who were positive for both HBsAg and anti-HBs. Of these, one patient had only wild-type HBV, three had a viral mixture, and five had only 'a' epitope variant HBV. Of the three patients with a viral mixture, all had variants in the less conserved region (123-137). Of the five patients with pure HBsAg mutants, three had variants in the less conserved region while two had variants in the highly conserved region. In this study with a limited number of patients, the serum alanine aminotransferase (ALT) levels were higher in patients with wild-type HBV, compared with those with either 'a' epitope variants or a viral mixture consisting of wild type and variants. Eight of the nine (89%) patients positive for both HBsAg and anti-HBs harbored an 'a' epitope variant. The lower ALT levels seen in patients who had either pure 'a' epitope variant or a mixture of wild type and mutants suggest that a closer monitoring of these 'a' epitope variants should be required, as patients carrying these infectious viral strains may remain asymptomatic.

A review of enzyme changes in serum and urine due to treatment with drugs (tuberculostatics, contraceptive medication, diagnostics and drugs in real diseases).

PubMed

Haschen, R J

1980-01-01

Serum enzymes are sensitive tools for demonstration of injury to different organs of the body, including lesions that are side effects of drugs or the application of certain compounds for diagnostic purposes. It has been reported that tuberculosis therapy can cause liver damage of the unpredictable drug-induced liver lesion-type. The liver lesions due to tuberculostatics resemble an unspecific or viral hepatitis. Oral contraceptives can also cause hepatic lesions, some of them being quite serious. They have been known to cause hepatosis with or without cholestasis, drug-induced hepatitis, circulatory disturbances such as hepatic peliosis and Budd-Chiari syndrome, and benign and malignant tumors. Therapy control should be instituted in these cases. Enzymes can be used as indicators. A considerable increase of coeruloplasmin (or serum copper) is a useful marker for monitoring contraceptive medication; the aminotransferases initially show a slight increase while later, they may be decreasing to subnormal values. The appearance of serious morphological findings may necessitate delineation of normal ranges and alarm ranges. Serial enzyme determinations are suggested in: 1) high risk patients who have been suffering from hepatitis or intrahepatic cholestasis due to pregnancy or drugs, and 2) in persons complaining of signs or symptoms suggestive of liver involvement. The kidney is another organ which might be influenced by certain drugs leaving the organism via the urinary tract. The presence of enzymes in urine can serve as sensitive indicators of a proximal tubular lesion. The effects of certain hormones on the kidneys are discussed.

Assessment of hepatitis B virus and hepatitis C virus infections and associated risk factors in HIV infected patients at Debretabor hospital, South Gondar, Northwest Ethiopia

PubMed Central

Balew, Melashu; Moges, Feleke; Yismaw, Gizachew; Unakal, Chandrashekhar

2014-01-01

Objective To assess hepatitis B and hepatitis C virus infections and associated risk factors among HIV infected patients at Debretabor hospital. Methods A cross-sectional study was conducted among HIV/AIDS patients attending Debretabor hospital from February to April, 2012. Venous blood samples were collected from study participants for HBsAg and anti HCV antibody tests. Bivariate and multivariate analyses were used to identify associated variables with HBsAg and anti HCV positivity. Variables having P<0.05 was taken as statistically significant association. Results From a total of 395 HIV infected patients included in this study, 234 (59.2%) were females and 161 (40.8%) males with mean (±SD) age of 36.31 (±9.91) years. The prevalence of HBsAg and anti HCV antibody was 6.1% and 1.3%, respectively. In multivariate analysis, multiple sexual partner (AOR=8.1, 95% CI=1.8-33.97) and history of opportunistic infections (AOR=3.17, 95% CI=1.3-7.7) were statistically associated with HBsAg positivity. History of blood transfusion (AOR=5.61, 95% CI= 1.03-36.59) was associated with presence of anti-HCV antibody. Conclusions The prevalence of HBsAg and anti HCV antibodies in HIV coinfected patients was intermediate. However, it is relevant for HIV infected patients since viral hepatitis co-infections in HIV patients can cause multiple complications. Therefore, routine HBV and HCV screening with reliable diagnostic markers need to be carried out for close monitoring and better management in HIV patients.

Spectral-decomposition techniques for the identification of radon anomalies temporally associated with earthquakes occurring in the UK in 2002 and 2008.

NASA Astrophysics Data System (ADS)

Crockett, R. G. M.; Gillmore, G. K.

2009-04-01

During the second half of 2002, the University of Northampton Radon Research Group operated two continuous hourly-sampling radon detectors 2.25 km apart in Northampton, in the (English) East Midlands. This period included the Dudley earthquake (22/09/2002) which was widely noticed by members of the public in the Northampton area. Also, at various periods during 2008 the Group has operated another pair of continuous hourly-sampling radon detectors similar distances apart in Northampton. One such period included the Market Rasen earthquake (27/02/2008) which was also widely noticed by members of the public in the Northampton area. During each period of monitoring, two time-series of radon readings were obtained, one from each detector. These have been analysed for evidence of simultaneous similar anomalies: the premise being that big disturbances occurring at big distances (in relation to the detector separation) should produce simultaneous similar anomalies but that simultaneous anomalies occurring by chance will be dissimilar. As previously reported, cross-correlating the two 2002 time-series over periods of 1-30 days duration, rolled forwards through the time-series at one-hour intervals produced two periods of significant correlation, i.e. two periods of simultaneous similar behaviour in the radon concentrations. One of these periods corresponded in time to the Dudley earthquake, the other corresponded in time to a smaller earthquake which occurred in the English Channel (26/08/2002). We here report subsequent investigation of the 2002 time-series and the 2008 time-series using spectral-decomposition techniques. These techniques have revealed additional simultaneous similar behaviour in the two radon concentrations, not revealed by the rolling correlation on the raw data. These correspond in time to the Manchester earthquake swarm of October 2002 and the Market Rasen earthquake of February 2008. The spectral-decomposition techniques effectively ‘de-noise' the data, and also remove lower-frequency variations (e.g. tidal variations), revealing the simultaneous similarities. Whilst this is very much work in progress, there is the potential that such techniques enhance the possibility that simultaneous real-time monitoring of radon levels - for short-term simultaneous anomalies - at several locations in earthquake areas might provide the core of an earthquake prediction method. Keywords: Radon; earthquakes; time series; cross-correlation; spectral-decomposition; real-time simultaneous monitoring.

Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury.

PubMed

Kim, Jin Yong; Lee, Dong Yun; Kang, Sukmo; Miao, Wenjun; Kim, Hyungjun; Lee, Yonghyun; Jon, Sangyong

2017-07-01

Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress. BRNPs exerted potent antioxidant and anti-apoptotic activity in primary hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species (ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound protective effects against hepatocellular injury by reducing oxidative stress, pro-inflammatory cytokine production, and recruitment of neutrophils. They also preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our findings indicate that BRNP preconditioning provides a simple and safe approach that can be easily monitored in the blood like endogenous bilirubin, and could be a promising strategy to protect against IRI in a clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS).

PubMed

Teshale, E; Lu, M; Rupp, L B; Holmberg, S D; Moorman, A C; Spradling, P; Vijayadeva, V; Boscarino, J A; Schmidt, M A; Gordon, S C

2014-12-01

We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis. © 2014 John Wiley & Sons Ltd.

Hepatitis B surface antigen gene expression is regulated by sex steroids and glucocorticoids in transgenic mice.

PubMed Central

Farza, H; Salmon, A M; Hadchouel, M; Moreau, J L; Babinet, C; Tiollais, P; Pourcel, C

1987-01-01

We have investigated the basis for liver-specific and sex-linked expression of hepatitis B surface antigen (HBsAg) gene in transgenic mice by monitoring the level of liver HBsAg mRNA and serum HBsAg at different stages of development and in response to sex-hormone regulation. Transcription of the HBsAg gene starts at day 15 of development, together with that of the albumin gene, and reaches a comparable level at birth. HBsAg mRNA level and HBsAg production are parallel in males and females during prenatal development and until the first month of life, but HBsAg gene expression increases 5-10 times in males at puberty. After castration, the level of expression decreases dramatically in both males and females and is subsequently increased by injection of testosterone or estradiol. Glucocorticoids also regulated positively expression of the HBsAg gene. Our results suggest that sex hormones play a role in hepatitis B virus gene expression during natural infection and could explain the difference in incidence of chronic carriers between men and women. Images PMID:3469661

Formation of Δ(1) and Δ(6) testosterone metabolites by human hepatocytes.

PubMed

Fabregat, Andreu; Marcos, Josep; Ventura, Rosa; Casals, Gregori; Jimenez, Wladimiro; Reichenbach, Vedrana; Segura, Jordi; Pozo, Oscar J

2015-03-01

The existence of urinary testosterone (T) metabolites conjugated with cysteine has been recently reported. The formation of a ring double bond by a phase I metabolic transformation and the subsequent nucleophilic conjugation with glutathione was proposed as a putative metabolic pathway for the occurrence of these metabolites in urine. The main goal of the present study was to confirm the first step of the postulated pathway. For that purpose, human hepatocyte cells systems were incubated with a pure T standard. The cell culture supernatants were analyzed by liquid chromatography coupled to mass spectrometry using a selected reaction monitoring method. Major T metabolites such as androsterone and 4-androstene-3,17-dione, together with the recently reported Δ(1) and Δ(6) metabolites were simultaneously quantified. The formation of 1,4-androstadien-3,17-dione, 4,6-androstadien-3,17-dione, 17β-hydroxy-4,6-androstadien-3-one and 17β-hydroxy-1,4-androstadien-3-one (boldenone) after incubation of T in hepatocyte cell cultures was demonstrated by comparing the retention times and the ion ratios of the metabolites with those obtained by analysis of commercial standards. Thus, the formation of double bonds Δ(1) and Δ(6) by hepatic phase I metabolism of T was confirmed. Analogously to T, this pathway might also be present in other steroids, opening the possibility of targeting additional biomarkers. Copyright © 2015. Published by Elsevier Inc.

Influence of protein ingestion on human splanchnic and whole-body oxygen consumption, blood flow, and blood temperature.

PubMed

Brundin, T; Wahren, J

1994-05-01

Splanchnic and whole-body oxygen uptake, blood flow, and blood temperature were studied in 10 healthy subjects before and during 2 hours after oral ingestion of 900 kJ of fish protein. Indirect calorimetry and catheter techniques were used, including blood thermometry in arterial, pulmonary arterial, and hepatic venous blood. After the meal, pulmonary oxygen uptake increased from a basal value of 272 +/- 11 to 332 +/- 23 mL/min. During the first postprandial hour, splanchnic oxygen uptake increased from 62 +/- 5 to 93 +/- 9 mL/min (+50%, P < .05), thereby accounting for 62% +/- 17% of the simultaneous increase in whole-body oxygen consumption. During the second postprandial hour, splanchnic oxygen uptake increased no further, whereas in the extrasplanchnic tissues the oxygen consumption increased, now accounting for the entire simultaneous increase in pulmonary oxygen uptake. Cardiac output increased from basal 6.4 +/- 0.4 to 7.5 +/- 0.5 L/min. Splanchnic blood flow changed little while the arteriohepatic venous oxygen difference increased from 46 +/- 3 to 54 +/- 4 mL/L. Arterial and hepatic venous blood temperatures increased by almost 0.3 degrees C, reflecting a considerable accumulation of heat, indicating a conversion into a positive thermal balance. It is concluded that after protein ingestion, (1) oxygen uptake increases mainly in the splanchnic organs during the first hour, and thereafter exclusively in the extrasplanchnic tissues; (2) the blood flow increases mainly in extrasplanchnic tissues; and (3) the blood temperature increases almost linearly, indicating an upward adjustment of the temperature setpoint in the central thermosensors.

Atypical PKC, PKCλ/ι, activates β-secretase and increases Aβ1-40/42 and phospho-tau in mouse brain and isolated neuronal cells, and may link hyperinsulinemia and other aPKC activators to development of pathological and memory abnormalities in Alzheimer's disease.

PubMed

Sajan, Mini P; Hansen, Barbara C; Higgs, Margaret G; Kahn, C Ron; Braun, Ursula; Leitges, Michael; Park, Collin R; Diamond, David M; Farese, Robert V

2018-01-01

Hyperinsulinemia activates brain Akt and PKC-λ/ι and increases Aβ 1-40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Aβ 1-40/42 , β-secretase activity was increased in insulin-resistant mice and monkeys. In insulin-resistant mice, inhibition of hepatic PKC-λ/ι sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously reversed increases in Akt, atypical protein kinase C (aPKC), β-secretase, and Aβ 1-40/42 , and restored acute Akt activation. However, 2 aPKC inhibitors additionally blocked insulin's ability to activate brain PKC-λ/ι and thereby increase β-secretase and Aβ 1-40/42 . Furthermore, direct blockade of brain aPKC simultaneously corrected an impairment in novel object recognition in high-fat-fed insulin-resistant mice. In neuronal cells and/or mouse hippocampal slices, PKC-ι/λ activation by insulin, metformin, or expression of constitutive PKC-ι provoked increases in β-secretase, Aβ 1-40/42 , and phospho-thr-231-tau that were blocked by various PKC-λ/ι inhibitors, but not by an Akt inhibitor. PKC-λ/ι provokes increases in brain β-secretase, Aβ 1-40/42 , and phospho-thr-231-tau. Excessive signaling via PKC-λ/ι may link hyperinsulinemia and other PKC-λ/ι activators to pathological and functional abnormalities in Alzheimer's disease. Published by Elsevier Inc.

Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

EPA Science Inventory

There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

Predicting US Drought Monitor (USDM) states using precipitation, soil moisture, and evapotranspiration anomalies, Part I: Development of a non-discrete USDM index

USDA-ARS?s Scientific Manuscript database

The U.S. Drought Monitor (USDM) classifies drought into five discrete dryness/drought categories based on expert synthesis of numerous data sources. In this study, an empirical methodology is presented for creating a non-discrete U.S. Drought Monitor (USDM) index that simultaneously 1) represents th...

Layered acoustofluidic resonators for the simultaneous optical and acoustic characterisation of cavitation dynamics, microstreaming, and biological effects.

PubMed

Pereno, V; Aron, M; Vince, O; Mannaris, C; Seth, A; de Saint Victor, M; Lajoinie, G; Versluis, M; Coussios, C; Carugo, D; Stride, E

2018-05-01

The study of the effects of ultrasound-induced acoustic cavitation on biological structures is an active field in biomedical research. Of particular interest for therapeutic applications is the ability of oscillating microbubbles to promote both cellular and tissue membrane permeabilisation and to improve the distribution of therapeutic agents in tissue through extravasation and convective transport. The mechanisms that underpin the interaction between cavitating agents and tissues are, however, still poorly understood. One challenge is the practical difficulty involved in performing optical microscopy and acoustic emissions monitoring simultaneously in a biologically compatible environment. Here we present and characterise a microfluidic layered acoustic resonator ( μ LAR) developed for simultaneous ultrasound exposure, acoustic emissions monitoring, and microscopy of biological samples. The μ LAR facilitates in vitro ultrasound experiments in which measurements of microbubble dynamics, microstreaming velocity fields, acoustic emissions, and cell-microbubble interactions can be performed simultaneously. The device and analyses presented provide a means of performing mechanistic in vitro studies that may benefit the design of predictable and effective cavitation-based ultrasound treatments.

Simultaneous radiofrequency (RF) heating and magnetic resonance (MR) thermal mapping using an intravascular MR imaging/RF heating system.

PubMed

Qiu, Bensheng; El-Sharkawy, Abdel-Monem; Paliwal, Vaishali; Karmarkar, Parag; Gao, Fabao; Atalar, Ergin; Yang, Xiaoming

2005-07-01

Previous studies have confirmed the possibility of using an intravascular MR imaging guidewire (MRIG) as a heating source to enhance vascular gene transfection/expression. This motivated us to develop a new intravascular system that can perform MR imaging, radiofrequncy (RF) heating, and MR temperature monitoring simultaneously in an MR scanner. To validate this concept, a series of mathematical simulations of RF power loss along a 0.032-inch MRIG and RF energy spatial distribution were performed to determine the optimum RF heating frequency. Then, an RF generator/amplifier and a filter box were built. The possibility for simultaneous RF heating and MR thermal mapping of the system was confirmed in vitro using a phantom, and the obtained thermal mapping profile was compared with the simulated RF power distribution. Subsequently, the feasibility of simultaneous RF heating and temperature monitoring was successfully validated in vivo in the aorta of living rabbits. This MR imaging/RF heating system offers a potential tool for intravascular MR-mediated, RF-enhanced vascular gene therapy.

Process monitored spectrophotometric titration coupled with chemometrics for simultaneous determination of mixtures of weak acids.

PubMed

Liao, Lifu; Yang, Jing; Yuan, Jintao

2007-05-15

A new spectrophotometric titration method coupled with chemometrics for the simultaneous determination of mixtures of weak acids has been developed. In this method, the titrant is a mixture of sodium hydroxide and an acid-base indicator, and the indicator is used to monitor the titration process. In a process of titration, both the added volume of titrant and the solution acidity at each titration point can be obtained simultaneously from an absorption spectrum by least square algorithm, and then the concentration of each component in the mixture can be obtained from the titration curves by principal component regression. The method only needs the information of absorbance spectra to obtain the analytical results, and is free of volumetric measurements. The analyses are independent of titration end point and do not need the accurate values of dissociation constants of the indicator and the acids. The method has been applied to the simultaneous determination of the mixtures of benzoic acid and salicylic acid, and the mixtures of phenol, o-chlorophenol and p-chlorophenol with satisfactory results.

Development of an alpha/beta/gamma detector for radiation monitoring

NASA Astrophysics Data System (ADS)

Yamamoto, Seiichi; Hatazawa, Jun

2011-11-01

For radiation monitoring at the site of nuclear power plant accidents such as Fukushima Daiichi, radiation detectors not only for gamma photons but also for alpha and beta particles are needed because some nuclear fission products emit beta particles and gamma photons and some nuclear fuels contain plutonium that emits alpha particles. We developed a radiation detector that can simultaneously monitor alpha and beta particles and gamma photons for radiation monitoring. The detector consists of three-layered scintillators optically coupled to each other and coupled to a photomultiplier tube. The first layer, which is made of a thin plastic scintillator (decay time: 2.4 ns), detects alpha particles. The second layer, which is made of a thin Gd2SiO5 (GSO) scintillator with 1.5 mol.% Ce (decay time: 35 ns), detects beta particles. The third layer made of a thin GSO scintillator with 0.4 mol.% Ce (decay time: 70 ns) detects gamma photons. By using pulse shape discrimination, the count rates of these layers can be separated. With individual irradiation of alpha and beta particles and gamma photons, the count rate of the first layer represented the alpha particles, the second layer represented the beta particles, and the third layer represented the gamma photons. Even with simultaneous irradiation of the alpha and beta particles and the gamma photons, these three types of radiation can be individually monitored using correction for the gamma detection efficiency of the second and third layers. Our developed alpha, beta, and gamma detector is simple and will be useful for radiation monitoring, especially at nuclear power plant accident sites or other applications where the simultaneous measurements of alpha and beta particles and gamma photons are required.

Development of an alpha/beta/gamma detector for radiation monitoring.

PubMed

Yamamoto, Seiichi; Hatazawa, Jun

2011-11-01

For radiation monitoring at the site of nuclear power plant accidents such as Fukushima Daiichi, radiation detectors not only for gamma photons but also for alpha and beta particles are needed because some nuclear fission products emit beta particles and gamma photons and some nuclear fuels contain plutonium that emits alpha particles. We developed a radiation detector that can simultaneously monitor alpha and beta particles and gamma photons for radiation monitoring. The detector consists of three-layered scintillators optically coupled to each other and coupled to a photomultiplier tube. The first layer, which is made of a thin plastic scintillator (decay time: 2.4 ns), detects alpha particles. The second layer, which is made of a thin Gd(2)SiO(5) (GSO) scintillator with 1.5 mol.% Ce (decay time: 35 ns), detects beta particles. The third layer made of a thin GSO scintillator with 0.4 mol.% Ce (decay time: 70 ns) detects gamma photons. By using pulse shape discrimination, the count rates of these layers can be separated. With individual irradiation of alpha and beta particles and gamma photons, the count rate of the first layer represented the alpha particles, the second layer represented the beta particles, and the third layer represented the gamma photons. Even with simultaneous irradiation of the alpha and beta particles and the gamma photons, these three types of radiation can be individually monitored using correction for the gamma detection efficiency of the second and third layers. Our developed alpha, beta, and gamma detector is simple and will be useful for radiation monitoring, especially at nuclear power plant accident sites or other applications where the simultaneous measurements of alpha and beta particles and gamma photons are required. © 2011 American Institute of Physics

Abacavir/Dolutegravir/Lamivudine (Triumeq)-Induced Liver Toxicity in a Human Immunodeficiency Virus-Infected Patient.

PubMed

Christensen, Erin S; Jain, Rupali; Roxby, Alison C

2017-01-01

Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.

Measurement of diabetic sugar concentration in human blood using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Firdous, S.; Nawaz, M.; Ahmed, M.; Anwar, S.; Rehman, A.; Rashid, R.; Mahmood, A.

2012-06-01

This study demonstrates the use of Raman spectroscopy for the direct measurement of diabetic sugar in human blood using 532 nm laser system. Raman spectra were collected from whole blood drawn from 21 individuals. We have elicited a reliable glucose signature in diabetic patients, and measured glucose levels in blood serum of normal, healthy diabetic and diabetic patients with other malignancies like cancer and hepatitis. Quantitative predictions of glucose spectra illustrate the predictions based on molecular information carried by the Raman light in highly light-scattering and absorbing media. Raman spectrum peaks for diabetic blood serum are observed at 1168, 1531, 1463, 1021 cm-1 with intensity level 17000 to 18500 pixels attributed to carbohydrates, proteins, lipids, collagen, and skeletal C-C stretch of lipids acyl chains. Raman spectra for normal, diabetic patients having cancer and hepatitis were also recorded. This in vitro glucose monitoring methodology will lead in vivo noninvasive on-line monitoring having painless and at the same time the data will be displayed on-line and in real time. The measured Raman peaks provides detailed bio-chemical fingerprint of the sample and could confer diagnostic benefit in a clinical setting.

Hepatitis B vaccine freezing in the Indonesian cold chain: evidence and solutions.

PubMed

Nelson, Carib M; Wibisono, Hariadi; Purwanto, Hary; Mansyur, Isa; Moniaga, Vanda; Widjaya, Anton

2004-02-01

To document and characterize freezing temperatures in the Indonesian vaccine cold chain and to evaluate the feasibility of changes designed to reduce the occurrence of freezing. Data loggers were used to measure temperatures of shipments of hepatitis B vaccine from manufacturer to point of use. Baseline conditions and three intervention phases were monitored. During each of the intervention phases, vaccines were removed progressively from the standard 2-8 degrees C cold chain. Freezing temperatures were recorded in 75% of baseline shipments. The highest rates of freezing occurred during transport from province to district, storage in district-level ice-lined refrigerators, and storage in refrigerators in health centres. Interventions reduced freezing, without excessive heat exposure. Inadvertent freezing of freeze-sensitive vaccines is widespread in Indonesia. Simple strategies exist to reduce freezing - for example, selective transport and storage of vaccines at ambient temperatures. The use of vaccine vial monitors reduces the risk associated with heat-damaged vaccines in these scenarios. Policy changes that allow limited storage of freeze-sensitive vaccines at temperatures >2-8 degrees C would enable flexible vaccine distribution strategies that could reduce vaccine freezing, reduce costs, and increase capacity.

Hospital-based allogenic bone bank--10-year experience.

PubMed

Hou, C-H; Yang, R-S; Hou, S-M

2005-01-01

Bone banking in a hospital provides resources of allogenic bone grafts. However, they may transmit infection from donor to recipient. We found few reports discussing the infection rate and monitoring processes associated with bone banks. The discard rate using the screening test was 18.5% (309/1674) in this series. The leading cause was hepatitis B antigen (HBsAg) positive donor serum (67%), followed by Venereal Disease Research Laboratory (VDRL) positive donor serum (15%), and anti-hepatitis C virus (HCV) positive donor serum (12%). The overall infection rate in the recipients was 1.3% (17/1365). Among 1353 implanted allografts, 22 cases (1.6%) had a positive swab culture result after thawing. Only four out of these 22 cases (18.2%) developed infection. However, the wound cultures of the infected recipients were different from the swab culture of thawing allografts except in one case. Among the 1331 recipients with sterile allograft bones, 13 (1%) were found to have infection. In conclusion, our bone bank operates under a strict monitoring system which results in a low infection rate. The recipient's status, the aseptic technique and environment during operation is likely to be more critical in prevention of allograft-related infection.

Five-year antibody persistence in children after one dose of inactivated or live attenuated hepatitis A vaccine.

PubMed

Zhang, Zhilun; Zhu, Xiangjun; Hu, Yuansheng; Liang, Miao; Sun, Jin; Song, Yufei; Yang, Qi; Ji, Haiquan; Zeng, Gang; Song, Lifei; Chen, Jiangting

2017-06-03

In China, both inactivated hepatitis A (HA) vaccine and live attenuated HA vaccine are available. We conducted a trial to evaluate 5-year immune persistence induced by one dose of inactivated or live attenuated HA vaccines in children. Subjects with no HA vaccination history had randomly received one dose of inactivated or live attenuated HA vaccine at 18-60 months of age. Anti-HAV antibody concentrations were measured before vaccination and at the first, second, and fifth year after vaccination. Suspected cases of hepatitis A were monitored during the study period. A total of 332 subjects were enrolled and 182 provided evaluable serum samples at all planned time points. seropositive rate at 5 y was 85.9% in the inactivated HA vaccine group and 90.7% in the live attenuated HA vaccine group. GMCs were 76.3% mIU/ml (95% CI: 61.7 - 94.4) and 66.8mIU/ml (95% CI: 57.8 - 77.3), respectively. No significant difference in antibody persistence between 2 groups was found. No clinical hepatitis A case was reported. A single dose of an inactivated or live attenuated HA vaccine at 18-60 months of age resulted in high HAV seropositive rate and anti-HAV antibody concentrations that lasted for at least 5 y.

Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents.

PubMed

Labine, Meaghan; Gong, Yuewen; Minuk, Gerald Y

Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis.

Drug metabolism and ageing.

PubMed

Wynne, Hilary

2005-06-01

Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

Survival and risk factors related to death in outpatients with cirrhosis treated in a clinic in Southern Brazil.

PubMed

John, Jorge Alberto; de Mattos, Angelo Alves; da Silva Miozzo, Suelen Aparecida; Comerlato, Pedro Henrique; Porto, Mariana; Contiero, Priscila; da Silva, Renata Rodrigues

2015-12-01

Cirrhosis represents a public health issue that generally evolves and presents serious complications. To assess the outcomes of outpatients with cirrhosis. We used a retrospective outpatient-based cohort, assessing 527 patients with cirrhosis. Demographic, clinical, and laboratory variables were analyzed, as well as the risk factors related to death, using the Cox proportional-hazard regression model. The Kaplan-Meier method was used to analyze survival rates. Patients had a mean age of 52.9±9.7 years and were more frequently men (59%), presenting Child-Turcotte-Pugh B or C in 43% of the cases in addition to a mean Model for End-Stage Liver Disease score of 12.0±4.1. The predominant etiology of liver disease was the hepatitis C virus. The most frequent complications during follow-up were ascites (34%), hepatic encephalopathy (17%), and hepatocellular carcinoma (17%). The survival rate at years 5 and 10 was 73 and 57%, respectively. The main risk factors that were related to death were, in a multivariate analysis, hepatitis C virus etiology, presence of hepatocellular carcinoma, and serum levels of albumin. Patients with cirrhosis monitored on an outpatient basis, despite showing a reasonable survival rate, have a worse prognosis when the etiology of liver disease is related to hepatitis C virus and when they have hepatocellular carcinoma or hypoalbuminemia.

Development of candidate combination vaccine for hepatitis E and hepatitis B: a liposome encapsulation approach.

PubMed

Shrivastava, Shubham; Lole, Kavita S; Tripathy, Anuradha S; Shaligram, Umesh S; Arankalle, Vidya A

2009-11-05

To reduce extra injections, cost and ensure better coverage, use of combination vaccines is preferable. An attempt was made to evaluate the encapsulation of hepatitis E virus neutralizing epitope (NE) region and hepatitis B virus surface antigen (HBsAg) in liposomes as DNAs, proteins and DNA+protein. Mice groups were immunized with different liposome-encapsulated formulations and monitored for anti-HEV and anti-HBs titres, IgG subtypes, antigen-specific lymphocyte proliferation and cytokine levels. The protective levels of anti-HBs and in vitro virus-binding capacity of anti-HEV antibodies were assessed. Liposome-encapsulated DNA either singly or in combination did not elicit antibody response. Anti-HEV and anti-HBs IgG titres of individual component of protein alone (Lipo-E-P/Lipo-B-P) or DNA+protein formulations (Lipo-E-DP/Lipo-B-DP) were comparable to respective titres in combination vaccine of protein (Lipo-BE-P) and DNA+protein formulations (Lipo-BE-DP). IgG1 levels were significantly higher in Lipo-BE-P group whereas, equivalent levels of IgG1 and IgG2a were observed in Lipo-BE-DP group against both components of the vaccine. Combination vaccine group showed mixed Th1/Th2 cytokine profile. Liposome entrapped NE and HBsAg in protein and DNA+protein formats induce excellent immune response to both the components and need to be evaluated in higher animals.

Hepatitis C Virus: A Critical Appraisal of New Approaches to Therapy

PubMed Central

Nelson, David R.; Jensen, Donald M.; Sulkowski, Mark S.; Everson, Greg; Fried, Michael W.; Gordon, Stuart C.; Jacobson, Ira; Reau, Nancy S.; Sherman, Kenneth; Terrault, Nora; Thomas, David

2012-01-01

The HCV council 2011 convened 11 leading clinicians and researchers in hepatitis C virus from academic medical centers in the United States to provide a forum for the practical and comprehensive evaluation of current data regarding best practices for integrating new direct-acting antiviral agents into existing treatment paradigms. The council investigated 10 clinical practice statements related to HCV treatment that reflect key topical areas. Faculty members reviewed and discussed the data related to each statement, and voted on the nature of the evidence and their level of support for each statement. In this new era of DAAs, a comprehensive and critical analysis of the literature is needed to equip clinicians with the knowledge necessary to design, monitor, and modify treatment regimens in order to optimize patient outcomes. PMID:23094146

BAsE-Seq: a method for obtaining long viral haplotypes from short sequence reads.

PubMed

Hong, Lewis Z; Hong, Shuzhen; Wong, Han Teng; Aw, Pauline P K; Cheng, Yan; Wilm, Andreas; de Sessions, Paola F; Lim, Seng Gee; Nagarajan, Niranjan; Hibberd, Martin L; Quake, Stephen R; Burkholder, William F

2014-01-01

We present a method for obtaining long haplotypes, of over 3 kb in length, using a short-read sequencer, Barcode-directed Assembly for Extra-long Sequences (BAsE-Seq). BAsE-Seq relies on transposing a template-specific barcode onto random segments of the template molecule and assembling the barcoded short reads into complete haplotypes. We applied BAsE-Seq on mixed clones of hepatitis B virus and accurately identified haplotypes occurring at frequencies greater than or equal to 0.4%, with >99.9% specificity. Applying BAsE-Seq to a clinical sample, we obtained over 9,000 viral haplotypes, which provided an unprecedented view of hepatitis B virus population structure during chronic infection. BAsE-Seq is readily applicable for monitoring quasispecies evolution in viral diseases.

[Experimental rationale for a procedure for correction of the residual cavity in hydatidectomy].

PubMed

Biriukov, Iu V; Streliaeva, A V; Sadykov, R V; Lazareva, N B; Sadykov, V M; Chebyshev, N V

2010-01-01

Thirty-six piglets (15 days old) were inoculated with Echinococcus according to the authors' procedure. Hepatic hydatid cyst growth in the piglets was ultrasonographically monitored 3 months after inoculation. In 15 piglets, the size of hepatic hydatid cysts was as high as 6.5 x 8.5 cm 5 months after infection. The cavity of larvocystic fibrous capsule was eliminated, by inverting the resection margins inward with interrupted catgut sutures. For content aspiration, the cystic bed was occasionally drained by a polyvinyl chloride tube with two side holes, which was brought outward through an individual incision. Thesubhepatic area was also drained by a "cigar" tampon through an individual incision. The wound healed in layers, tightly. Marginal resection of the liver was performed to stimulate regenerative processes in the resected area.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

PubMed Central

De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

2016-01-01

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

Age-related effects of heat stress on protective enzymes for peroxides and microsomal monooxygenase in rat liver.

PubMed Central

Ando, M; Katagiri, K; Yamamoto, S; Wakamatsu, K; Kawahara, I; Asanuma, S; Usuda, M; Sasaki, K

1997-01-01

To evaluate the age-related response of essential cell functions against peroxidative damage in hyperthermia, we studied the biochemical response to heat stress in both young and aged rats. Passive hyperthermia was immediately observed in rats after exposure to hot environments. In aged rats, the rectal temperature maintained thermal homeostasis and increased to the same degree as in young rats. In these aged animals, the damage from heat stress was more serious than in young animals. In aged rats under normal environmental conditions, hepatic cytosolic glutathione peroxidase (GSH peroxidase) activities were markedly higher than those activities in younger rats. Hepatic cytosolic GSH peroxidase activities were induced by heat stress in young rats but were decreased by hot environments in aged rats. Hepatic catalase activities in young rats were not affected by hot environments, whereas in aged rats, hepatic catalase activities were seriously decreased. Catalase activities in the kidney of aged rats were also reduced by hot environments. Lipid peroxidation in the liver was markedly induced in both young and aged rats. Because the protective enzymes for oxygen radicals in aged rats were decreased by hot environments, lipid peroxidation in the liver was highly induced. In aged rats, lipid peroxidation in intracellular structures such as mitochondria and microsomes was also markedly induced by hot environments. In both young and aged rats, hyperthermia greatly increased the development of hypertrophy and vacuolated degeneration in hepatic cells. In aged rats, both mitochondria and endoplasmic reticulum of the hepatic cells showed serious distortion in shape as a result of exposures to hot environments. Microsomal electron transport systems, such as cytochrome P450 monooxygenase activities, were seriously decreased by heat stress in aged rats but not in young rats. Although the mitochondrial electron transport systems were not affected by acute heat stress in young rats, their activities were simultaneously inhibited after long-lasting heat exposure. In isolated hepatic cells and polymorphonuclear leukocytes in animals, the 70-kDa heat shock-induced proteins were markedly increased by heat stress. In conclusion, the heat stress-inducible oxygen radical damage becomes more severe according to the age of rats. Because aging and hyperthermia have a synergistic effect on lipid peroxidation, protective enzyme activities for oxygen radicals may be essential for surviving and recovering from thermal injury in aged animals and also in humans. Images Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 3. Figure 4. Figure 5. Figure 6. A Figure 6. B Figure 7. A Figure 7. B PMID:9294719

Optical quasi-distributed simultaneous vibration and temperature sensing in stator bars of a 370-MVA electric generator

NASA Astrophysics Data System (ADS)

Dreyer, Uilian José; Vagner da Silva, Erlon; Martelli, Cicero; Cardozo da Silva, Jean Carlos

2017-08-01

In this paper, we propose a new multiparametric optical fiber transducer applied to an electric generator of 370 MVA. The optical transducer has three multiplexed FBGs in the same optical fiber as the sensing element. The FBG sensors can simultaneously measure both the temperature and vibration independently of the other multiplexed FBGs. The installation in the power plant was performed using six transducers and it was obtained 23 hours of simultaneous vibration and temperature measurement. All the FBGs used to monitor generator vibration were able to monitor the frequency of mechanical and electromagnetic vibrations, which were measured at 2 Hz and 120 Hz, respectively. During the measurement, the machine was turned off due to a failure and all the FBGs sensed temperature changes, as well as frequency vibration changes. The largest temperature difference measured between the FBGs during the test is approximately 2°C.

New developments in automated biosensing from remote water quality stations and satellite data retrieval for resources management

NASA Astrophysics Data System (ADS)

Morgan, E. L.; Eagleson, K. W.; Hermann, R.; McCollough, N. D.

1981-05-01

Maintaining adequate water quality in a multipurpose drainage system becomes increasingly important as demands on resources become greater. Real-time water quality monitoring plays a crucial role in meeting this objective. In addition to remote automated physical monitoring, developments at the end of the 1970's allow simultaneous real-time measurements of fish breathing response to water quality changes. These advantages complement complex in-stream surveys typically carried out to evaluate the environmental quality of a system. Automated biosensing units having remote capabilities are designed to aid in the evaluation of subtle water quality changes contributing to undesirable conditions in a drainage basin. Using microprocessor-based monitors to measure fish breathing rates, the biosensing units are interfaced to a U.S. National Aeronautics and Space Administration (N.A.S.A.) remote data collection platform for National Oceanic and Atmospheric Administration (N.O.A.A.) GOES satellite retrieval and transmission of data. Simultaneously, multiparameter physical information is collected from site-specific locations and recovered in a similar manner. Real-time biological and physical data received at a data processing center are readily available for interpretation by resource managers. Management schemes incorporating real-time monitoring networks into on-going programs to simultaneously retrieve biological and physical data by satellite, radio and telephone cable give added advantages in maintaining water quality for multipurpose needs.

Bird biodiversity assessments in temperate forest: the value of point count versus acoustic monitoring protocols.

PubMed

Klingbeil, Brian T; Willig, Michael R

2015-01-01

Effective monitoring programs for biodiversity are needed to assess trends in biodiversity and evaluate the consequences of management. This is particularly true for birds and faunas that occupy interior forest and other areas of low human population density, as these are frequently under-sampled compared to other habitats. For birds, Autonomous Recording Units (ARUs) have been proposed as a supplement or alternative to point counts made by human observers to enhance monitoring efforts. We employed two strategies (i.e., simultaneous-collection and same-season) to compare point count and ARU methods for quantifying species richness and composition of birds in temperate interior forests. The simultaneous-collection strategy compares surveys by ARUs and point counts, with methods matched in time, location, and survey duration such that the person and machine simultaneously collect data. The same-season strategy compares surveys from ARUs and point counts conducted at the same locations throughout the breeding season, but methods differ in the number, duration, and frequency of surveys. This second strategy more closely follows the ways in which monitoring programs are likely to be implemented. Site-specific estimates of richness (but not species composition) differed between methods; however, the nature of the relationship was dependent on the assessment strategy. Estimates of richness from point counts were greater than estimates from ARUs in the simultaneous-collection strategy. Woodpeckers in particular, were less frequently identified from ARUs than point counts with this strategy. Conversely, estimates of richness were lower from point counts than ARUs in the same-season strategy. Moreover, in the same-season strategy, ARUs detected the occurrence of passerines at a higher frequency than did point counts. Differences between ARU and point count methods were only detected in site-level comparisons. Importantly, both methods provide similar estimates of species richness and composition for the region. Consequently, if single visits to sites or short-term monitoring are the goal, point counts will likely perform better than ARUs, especially if species are rare or vocalize infrequently. However, if seasonal or annual monitoring of sites is the goal, ARUs offer a viable alternative to standard point-count methods, especially in the context of large-scale or long-term monitoring of temperate forest birds.

Personal carbon monoxide exposures of preschool children in Helsinki, Finland—comparison to ambient air concentrations

NASA Astrophysics Data System (ADS)

Alm, S.; Mukala, K.; Tiittanen, P.; Jantunen, M. J.

The associations of personal carbon monoxide (CO) exposures with ambient air CO concentrations measured at fixed monitoring sites, were studied among 194 children aged 3-6 yr in four downtown and four suburban day-care centers in Helsinki, Finland. Each child carried a personal CO exposure monitor between 1 and 4 times for a time period of between 20 and 24 h. CO concentrations at two fixed monitoring sites were measured simultaneously. The CO concentrations measured at the fixed monitoring sites were usually lower (mean maximum 8-h concentration: 0.9 and 2.6 mg m -3) than the personal CO exposure concentrations (mean maximum 8-h concentration: 3.3 mg m -3). The fixed site CO concentrations were poor predictors of the personal CO exposure concentrations. However, the correlations between the personal CO exposure and the fixed monitoring site CO concentrations increased (-0.03--0.12 to 0.13-0.16) with increasing averaging times from 1 to 8 h. Also, the fixed monitoring site CO concentrations explained the mean daily or weekly personal CO exposures of a group of simultaneously measured children better than individual exposure CO concentrations. This study suggests that the short-term CO personal exposure of children cannot be meaningfully assessed using fixed monitoring sites.

US EPA Base Study Standard Operating Procedure for Continuous Monitoring of Outdoor Air

EPA Pesticide Factsheets

The procedure described is intended for monitoring continuously and simultaneously outdoor air quality parameters that are most commonly associated with indoor air quality: the concentrations of carbon dioxide (CO2) and carbon monoxide (CO), temperature, nd relative humidity (RH).

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

Simultaneous dielectric monitoring of microfluidic channels at microwaves utilizing a metamaterial transmission line structure.

PubMed

Schüßler, M; Puentes, M; Dubuc, D; Grenier, K; Jakoby, R

2012-01-01

The paper presents a technique that allows the simultaneous monitoring of the dielectric properties of liquids in microfluidic channels at microwave frequencies. It is capable of being integrated within the lab-on-a-chip concept and uses a composite right/left-handed transmission line resonator which is detuned by the dielectric loading of the liquids in the channels. By monitoring the change in the resonance spectrum of the resonator the loading profile can be derived with the multi-resonant perturbation method. From the value of the dielectric constant inference on the substances like cells or chemicals in the channels can be drawn. The paper presents concept, design, fabrication and characterization of prototype sensors. The sensors have been designed to operate between 20 and 30 GHz and were tested with water and water ethanol mixtures.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

PubMed Central

Xuan, Shi-Ying; Xin, Yong-Ning; Chen, Hua; Shi, Guang-Jun; Guan, Hua-Shi; Li, Yang

2007-01-01

AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level. METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group). RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001). CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation. PMID:17465484

Dynamic measurement of fluorescent proteins spectral distribution on virus infected cells

NASA Astrophysics Data System (ADS)

Lee, Ja-Yun; Wu, Ming-Xiu; Kao, Chia-Yun; Wu, Tzong-Yuan; Hsu, I.-Jen

2006-09-01

We constructed a dynamic spectroscopy system that can simultaneously measure the intensity and spectral distributions of samples with multi-fluorophores in a single scan. The system was used to monitor the fluorescence distribution of cells infected by the virus, which is constructed by a recombinant baculoviruses, vAcD-Rhir-E, containing the red and green fluorescent protein gene that can simultaneously produce dual fluorescence in recombinant virus-infected Spodoptera frugiperda 21 cells (Sf21) under the control of a polyhedrin promoter. The system was composed of an excitation light source, a scanning system and a spectrometer. We also developed an algorithm and fitting process to analyze the pattern of fluorescence distribution of the dual fluorescence produced in the recombinant virus-infected cells. All the algorithm and calculation are automatically processed in a visualized scanning program and can monitor the specific region of sample by calculating its intensity distribution. The spectral measurement of each pixel was performed at millisecond range and the two dimensional distribution of full spectrum was recorded within several seconds. We have constructed a dynamic spectroscopy system to monitor the process of virus-infection of cells. The distributions of the dual fluorescence were simultaneously measured at micrometer resolution.

A European multicientre study on the comparison of HBV viral loads between VERIS HBV assay and Roche COBAS® TAQMAN® HBV test, Abbott RealTime HBV assay, Siemens VERSANT HBV assay, and Qiagen artus HBV RG kit.

PubMed

Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Izopet, Jacques; Lombardi, Alessandra; Marcos, MaAngeles; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

2017-10-01

Hepatitis B viral load testing is essential to treatment and monitoring decisions in patients with chronic Hepatitis B. Beckman Coulter has developed the VERIS HBV Assay (Veris) for use on the fully automated DxN VERIS Molecular Diagnostics System. 1 OBJECTIVES: To evaluate the clinical performance of the Veris HBV Assay at multiple EU laboratories STUDY DESIGN: Method comparison was performed with a total of 344 plasma specimens from HBV infected patients tested with Veris and COBAS ® TaqMan ® HBV Test (Cobas), 207 specimens tested with Veris and RealTime HBV Assay (RealTime), 86 specimens tested with Veris and VERSANT ® HBV Assay (Versant), and 74 specimens tested with Veris and artus ® HBV RG PCR kit (artus). Bland-Altman analysis showed average bias of -0.46 log 10 IU/mL between Veris and Cobas, -0.46 log 10 IU/mL between Veris and RealTime, -0.36 log 10 IU/mL between Veris and Versant, and -0.12 log 10 IU/mL between Veris and artus. Bias was consistent across the assay range. Patient monitoring results using Veris demonstrated similar viral load trends over time to Cobas, RealTime, and artus. The VERIS HBV Assay demonstrated comparable clinical performance, with varying degrees of negative bias, compared to other currently marketed assays for HBV DNA monitoring. This negative bias should be taken into consideration if switching monitoring methods to Veris. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection.

PubMed

Vermehren, Johannes; Susser, Simone; Berger, Annemarie; Perner, Dany; Peiffer, Kai-Henrik; Allwinn, Regina; Zeuzem, Stefan; Sarrazin, Christoph

2012-09-01

Virologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. The clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. We analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). Baseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1 log(10) reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2 log(10) decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. Determination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection. Copyright © 2012 Elsevier B.V. All rights reserved.

Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation.

PubMed

Takeichi, Takayuki; Asonuma, Katsuhiro; Kim, Ildeok; Inomata, Yukihiro; Kasahara, Mureo; Ohwada, Susumu; Morishita, Yasuo; Tanaka, Koichi

2002-08-01

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery from hepatic coma after liver transplantation.

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.

PubMed

Kong, Qin; Zhang, Haojun; Zhao, Tingting; Zhang, Weiku; Yan, Meihua; Dong, Xi; Li, Ping

2016-12-01

Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8‑week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity.

PubMed

Lunz, John G; Specht, Susan M; Murase, Noriko; Isse, Kumiko; Demetris, Anthony J

2007-12-01

Intraorgan dendritic cells (DCs) monitor the environment and help translate triggers of innate immunity into adaptive immune responses. Liver-based DCs are continually exposed, via gut-derived portal venous blood, to potential antigens and bacterial products that can trigger innate immunity. However, somehow the liver avoids a state of perpetual inflammation and protects central immune organs from overstimulation. In this study, we tested the hypothesis that hepatic interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activity increases the activation/maturation threshold of hepatic DCs toward innate immune signals. The results show that the liver nuclear STAT3 activity is significantly higher than that of other organs and is IL-6-dependent. Hepatic DCs in normal IL-6 wild-type (IL-6(+/+)) mice are phenotypically and functionally less mature than DCs from IL-6-deficient (IL-6(-/-)) or STAT3-inhibited IL-6(+/+) mice, as determined by surface marker expression, proinflammatory cytokine secretion, and allogeneic T-cell stimulation. IL-6(+/+) liver DCs produce IL-6 in response to exposure to lipopolysaccharide (LPS) and cytidine phosphate guanosine oligonucleotides (CpG) but are resistant to maturation compared with IL-6(-/-) liver DCs. Conversely, exogenous IL-6 inhibits LPS-induced IL-6(-/-) liver DC maturation. IL-6/STAT3 signaling influences the liver DC expression of toll-like receptor 9 and IL-1 receptor associated kinase-M. The depletion of gut commensal bacteria in IL-6(+/+) mice with oral antibiotics decreased portal blood endotoxin levels, lowered the expression of IL-6 and phospho-STAT3, and significantly increased liver DC maturation. Gut-derived bacterial products, by stimulating hepatic IL-6/STAT3 signaling, inhibit hepatic DC activation/maturation and thereby elevate the threshold needed for translating triggers of innate immunity into adaptive immune responses. Manipulating gut bacteria may therefore be an effective strategy for altering intrahepatic immune responses.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

PubMed

McDonald, S A; Hutchinson, S J; Innes, H A; Allen, S; Bramley, P; Bhattacharyya, D; Carman, W; Dillon, J F; Fox, R; Fraser, A; Goldberg, D J; Kennedy, N; Mills, P R; Morris, J; Stanley, A J; Wilks, D; Hayes, P C

2014-05-01

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect. © 2013 John Wiley & Sons Ltd.

Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh

PubMed Central

Tabassum, Shahina; Ullah Munshi, Saif; Hossain, Marufa; Imam, Akhter

2014-01-01

ABSTRACT Background and aim Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels. Materials and methods The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR. Results The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p < 0.01). Expression of PECAM-1 was positively correlated with serum ALT levels of both untreated (r = 0.580) and treated (r = 0.566) CHB patients. Moreover, in both untreated and treated groups, these gene expressions were positively correlated to serum HBV DNA load with the correlation coefficient r = 0.545 and r = 0.591 respectively. Conclusion PECAM-1 may be used as a biomarker for assessment of inflammatory activity as well as therapeutic response in CHB patients. How to cite this article: Sultana N, Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91. PMID:29699354

Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver.

PubMed

Rojas-Feria, María; Castro, Manuel; Suárez, Emilio; Ampuero, Javier; Romero-Gómez, Manuel

2013-11-14

Abnormal liver biochemical tests are present in up to 30% of patients with inflammatory bowel disease (IBD), and therefore become a diagnostic challenge. Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn's disease and ulcerative colitis (UC), and typically do not correlate with intestinal activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation of IBD, and is more prevalent in UC. Approximately 5% of patients with UC develop PSC, with the prevalence reaching up to 90%. Cholangiocarcinoma and colon cancer risks are increased in these patients. Less common disorders include autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cirrhosis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, liver abscess, and non-alcoholic fatty liver disease. Hepatitis B reactivation during immunosuppressive therapy is a major concern, with screening and vaccination being recommended in serologically negative cases for patients with IBD. Reactivation prophylaxis with entecavir or tenofovir for 6 to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen (HBsAg) positive, independently from viral load. HBsAg negative and anti-HBc positive patients, with or without anti-HBs, should be closely monitored, measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy, and should be treated if the viral load increases. On the other hand, immunosuppressive therapy does not seem to promote reactivation of hepatitis C, and hepatitis C antiviral treatment does not influence IBD natural history either. Most of the drugs used for IBD treatment may induce hepatotoxicity, although the incidence of serious adverse events is low. Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant. Methotrexate-related hepatotoxicity has been described in 14% of patients with IBD, in a dose-dependent manner. Liver biopsy is not routinely recommended. Biologics-related hepatotoxicity is rare, but has been shown most frequently in patients treated with infliximab. Thiopurines have been associated with veno-occlusive disease, regenerative nodular hyperplasia, and liver peliosis. Routine liver biochemical tests are recommended, especially during the first month of treatment. All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement. Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.

Clinical evaluation of the COBAS Ampliprep/COBAS TaqMan for HCV RNA quantitation in comparison with the branched-DNA assay.

PubMed

Pittaluga, Fabrizia; Allice, Tiziano; Abate, Maria Lorena; Ciancio, Alessia; Cerutti, Francesco; Varetto, Silvia; Colucci, Giuseppe; Smedile, Antonina; Ghisetti, Valeria

2008-02-01

Diagnosis and monitoring of HCV infection relies on sensitive and accurate HCV RNA detection and quantitation. The performance of the COBAS AmpliPrep/COBAS TaqMan 48 (CAP/CTM) (Roche, Branchburg, NJ), a fully automated, real-time PCR HCV RNA quantitative test was assessed and compared with the branched-DNA (bDNA) assay. Clinical evaluation on 576 specimens obtained from patients with chronic hepatitis C showed a good correlation (r = 0.893) between the two test, but the CAP/CTM scored higher HCV RNA titers than the bDNA across all viral genotypes. The mean bDNA versus CAP/CTM log10 IU/ml differences were -0.49, -0.4, -0.54, -0.26 for genotype 1a, 1b, 2a/2c, 3a, and 4, respectively. These differences reached statistical significance for genotypes 1b, 2a/c, and 3a. The ability of the CAP/CTM to monitor patients undergoing antiviral therapy and correctly identify the weeks 4 and 12 rapid and early virological responses was confirmed. The broader dynamic range of the CAP/CTM compared with the bDNA allowed for a better definition of viral kinetics. In conclusion, the CAP/CTM appears as a reliable and user-friendly assay to monitor HCV viremia during treatment of patients with chronic hepatitis. Its high sensitivity and wide dynamic range may help a better definition of viral load changes during antiviral therapy. (Copyright) 2007 Wiley-Liss, Inc.

Non-operative management versus operative management in high-grade blunt hepatic injury.

PubMed

Cirocchi, Roberto; Trastulli, Stefano; Pressi, Eleonora; Farinella, Eriberto; Avenia, Stefano; Morales Uribe, Carlos Hernando; Botero, Ana Maria; Barrera, Luis M

2015-08-24

Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. Two authors independently applied the selection criteria to relevant study reports. We used standard methodological procedures as defined by the Cochrane Collaboration. We were unable to find any randomised controlled trials of non-operative management versus operative management in high-grade blunt hepatic injury. In order to further explore the preliminary findings provided by animal models and observational clinical studies that suggests there may be a beneficial effect of non-operative management versus operative management in high-grade blunt hepatic injury, large, high quality randomised trials are needed.

Relative skills of soil moisture and vegetation optical depth retrievals for agricultural drought monitoring

USDA-ARS?s Scientific Manuscript database

Soil moisture condition is an important indicator for agricultural drought monitoring. Through the Land Parameter Retrieval Model (LPRM), vegetation optical depth (VOD) as well as surface soil moisture (SM) can be retrieved simultaneously from brightness temperature observations from the Advanced Mi...

Hepatitis B virus replication is upregulated in proliferated peripheral blood lymphocytes.

PubMed

Yan, Qin; Lan, Ying-Hua; Huang, Yan-Xin; Fan, Rong-Shan; Liu, Lan; Song, Shu-Peng; Li, Yong-Guo

2016-04-01

Increasing evidence indicates that the hepatitis B virus (HBV) replicates in peripheral blood mononuclear cells (PBMCs), but at a low level. The present study aimed to establish a reliable and sensitive method that effectively detects HBV viral products for monitoring antiviral therapy, organ transplantation screening, and diagnosing occult HBV infection. In the present study, PBMCs (obtained from six healthy volunteers) were inoculated with HBV, and cultured with phytohemagglutinin (PHA) and interleukin‑2 (IL‑2) to stimulate cell proliferation. PBMCs were harvested, and quantitative detection of HBV DNA in cell suspension and intracellular hepatitis B surface antigen (HBsAg) was conducted on days 0, 1, 6 and 12, respectively. In situ hybridization, immunohistochemistry and reverse transcription‑polymerase chain reaction (RT‑PCR) were performed to analyze the HBV infection. The results demonstrated that HBV DNA increased concurrently with proliferation of PBMCs isolated from three of six healthy volunteers, and the mean number of PBMCs on day 12 was 13.61 times higher than the initially seeded cell number (P<0.01). The mean copies of HBV DNA at day 12 were 2.98 times higher compared with initial levels (P<0.05). Furthermore, intracellular HBsAg levels increased concurrently with proliferation of PBMCs in one group of cultured PBMCs, which was accompanied by increased HBV DNA levels. In addition, HBV nucleic acids were detected in PBMCs using in situ hybridization. Intracellular HBsAg was observed in PBMCs and HBV RNA was also detected by RT‑PCR. The present study demonstrated that HBV replicates in proliferating PBMCs, which were induced by PHA and IL‑2. This method offers a novel investigative tool to detect HBV infection in PBMCs and to monitor the course of HBV infection.

Update on argatroban for the prophylaxis and treatment of heparin-induced thrombocytopenia type II

PubMed Central

Grouzi, Elisavet

2014-01-01

Heparin-induced thrombocytopenia (HIT) is a rare but potentially severe complication of heparin therapy that is strongly associated with venous and arterial thrombosis (HIT and thrombosis syndrome, HITTS), which requires urgent detection and treatment with a nonheparin anticoagulant. Argatroban, a synthetic direct thrombin inhibitor, is indicated for the treatment and prophylaxis of thrombosis in patients with HIT, including those undergoing percutaneous coronary intervention. Argatroban has a relatively short elimination half-life of approximately 45 minutes, which is predominantly performed via hepatic metabolism. It is derived from L-arginine that selectively and reversibly inhibits thrombin, both clot-bound and free, at the catalytic site. Argatroban anticoagulation has been systematically studied in patients with HIT and HITTS and proved to be a safe and effective agent for this indication. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from recent clinical trials with argatroban use in more special indications such as in percutaneous coronary intervention, liver dysfunction, renal replacement therapy, and intensive care medicine, are reviewed. The approved initial dosage of argatroban for adults with HIT or HITTS is 2 μg/kg/minute for patients with normal hepatic function and 0.5 μg/kg/minute for patients with hepatic dysfunction. There is evidence that a reduced initial dose may also be advisable for patients with heart failure, multiple organ dysfunction, severe anasarca, or after cardiac surgery. Given this information, argatroban can be effectively used in treating HIT with monitoring of activated partial thromboplastin time. PMID:25152637

Distinct features in natural history and outcomes of acute hepatitis C.

PubMed

Bunchorntavakul, Chalermrat; Jones, Lisa M; Kikuchi, Masahiro; Valiga, Mary E; Kaplan, David E; Nunes, Frederick A; Aytaman, Ayse; Reddy, K Rajender; Chang, Kyong-Mi

2015-04-01

Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

Hepatogastroenterologists' knowledge of inactive carriers and immunotolerant hepatitis B virus patients in France: results of a practice survey.

PubMed

Causse, Xavier; Cadranel, Jean-François; Potier, Pascal; Hanslik, Bertrand; Denis, Jacques; Renou, Christophe; Delasalle, Patrick

2015-05-01

Before the 2012 revision of the EASL guidelines for the management of hepatitis B virus infection, we conducted a survey to determine how French nonacademic hepatogastroenterologists defined inactive hepatitis B virus carriers and immunotolerant patients. We asked 680 hepatogastroenterologists to complete a simple survey consisting of 11 multiple-choice questions. The participation rate was 32%. HBeAg positivity was not identified as a key criterion for the diagnosis of immunotolerance by 61.9% of the respondents. A total of 82.5 and 75.9% of the respondents identified repeatedly normal alanine transaminase levels and repeatedly low viremia (<2000 IU/ml), respectively, as relevant criteria for the HBsAg inactive carrier state. The question on the biological monitoring of inactive carriers and immunotolerant patients was answered by 78% of the respondents, 97% of whom considered determinations of α-fetoprotein concentration and viremia every 6 (n=58, 35%) or 12 months (n=105, 63%) to be useful. Overall, 19% of the respondents declared never having treated an immunotolerant patient; 81% reported that they had treated such patients under some circumstances: 73% before immunosuppression or chemotherapy, 54% treated pregnant women in their third trimester when viremia was greater than 7 log IU/ml, 49% treated health professionals to prevent contamination, and 31% before medically assisted procreation. The definition of 'inactive carrier state' seems to have been well assimilated, but immunotolerance remains poorly understood. Biological monitoring was frequently carried out for inactive carriers and immunotolerant patients, but the diversity of the responses obtained highlights the lack of clear recommendations for the follow-up of these populations.

Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans.

PubMed

Britnell, Sara R; Willets, Amy E; Vanderman, Adam J; Woodard, Catherine L; Britt, Rachel B

2016-11-01

To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. Case series. Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System. Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes. © 2016 Pharmacotherapy Publications, Inc.

Assessing activity of Hepatitis A virus 3C protease using a cyclized luciferase-based biosensor.

PubMed

Zhou, Junwei; Wang, Dang; Xi, Yongqiang; Zhu, Xinyu; Yang, Yuting; Lv, Mengting; Luo, Chuanzhen; Chen, Jiyao; Ye, Xu; Fang, Liurong; Xiao, Shaobo

2017-07-08

Hepatitis A is an acute infection caused by Hepatitis A virus (HAV), which is widely distributed throughout the world. The HAV 3C cysteine protease (3C pro ), an important nonstructural protein, is responsible for most cleavage within the viral polyprotein and is critical for the processes of viral replication. Our group has previously demonstrated that HAV 3C pro cleaves human NF-κB essential modulator (NEMO), a kinase required in interferon signaling. Based on this finding, we generated four luciferase-based biosensors containing the NEMO sequence (PVLKAQ↓ADIYKA) that is cleaved by HAV 3C pro and/or the Nostoc punctiforme DnaE intein, to monitor the activity of HAV 3C pro in human embryonic kidney cells (HEK-293T). Western blotting showed that HAV 3C pro recognized and cleaved the NEMO cleavage sequence incorporated in the four biosensors, whereas only one cyclized luciferase-based biosensor (233-DnaE-HAV, 233DH) showed a measurable and reliable increase in firefly luciferase activity, with very low background, in the presence of HAV 3C pro . With this biosensor (233DH), we monitored HAV 3C pro activity in HEK-293T cells, and tested it against a catalytically deficient mutant HAV 3C pro and other virus-encoded proteases. The results showed that the activity of this luciferase biosensor is specifically dependent on HAV 3C pro . Collectively, our data demonstrate that the luciferase biosensor developed here might provide a rapid, sensitive, and efficient evaluation of HAV 3C pro activity, and should extend our better understanding of the biological relevance of HAV 3C pro . Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics and management of patients with chronic hepatitis B in an integrated care setting.

PubMed

Sarkar, Monika; Shvachko, Valentina A; Ready, Joanna B; Pauly, Mary Pat; Terrault, Norah A; Peters, Marion G; Manos, M Michele

2014-09-01

Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA. We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a "recent" 18-month study window (July 2009-December 2010), or as "ever" based on records dating to 1995. The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥ 1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment. Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting.

Effect of time spacing on the perceived color

NASA Astrophysics Data System (ADS)

Roch, Sylvain; Hardeberg, Jon Y.; Nussbaum, Peter

2007-01-01

One of latest developments for pre-press applications is the concept of soft proofing, which aims to provide an accurate preview on a monitor of how the final document will appear once it is printed. At the core of this concept is the problem of identifying, for any printed color, the most similar color the monitor can display. This problem is made difficult by such factors as varying viewing conditions, color gamut limitations, or the less studied time spacing. Color matching experiments are usually done by examining samples viewed simultaneously. However, in soft proofing applications, the proof and the print are not always viewed together. This paper attempts to shed more light on the difference between simultaneous and time-spaced color matching, in order to contribute to improving the accuracy of soft proofs. A color matching experiment setup has been established in which observers were asked to match a color patch displayed on a LCD monitor, by adjusting its RGB values, to another color patch printed out on paper. In the first part of the experiment the two colors were viewed simultaneously. In the second part, the observers were asked to produce the match according to a previously memorized color. According to the obtained results, the color appearance attributes lightness and chroma were the most difficult components for the observers to remember, generating huge differences with the simultaneous match, whereas hue was the component which varied the least. This indicates that for soft proofing, getting the hues right is of primordial importance.

Biomarker Discovery for Early Detection of Hepatocellular Carcinoma in Hepatitis C–infected Patients*

PubMed Central

Mustafa, Mehnaz G.; Petersen, John R.; Ju, Hyunsu; Cicalese, Luca; Snyder, Ned; Haidacher, Sigmund J.; Denner, Larry; Elferink, Cornelis

2013-01-01

Chronic hepatic disease damages the liver, and the resulting wound-healing process leads to liver fibrosis and the subsequent development of cirrhosis. The leading cause of hepatic fibrosis and cirrhosis is infection with hepatitis C virus (HCV), and of the patients with HCV-induced cirrhosis, 2% to 5% develop hepatocellular carcinoma (HCC), with a survival rate of 7%. HCC is one of the leading causes of cancer-related death worldwide, and the poor survival rate is largely due to late-stage diagnosis, which makes successful intervention difficult, if not impossible. The lack of sensitive and specific diagnostic tools and the urgent need for early-stage diagnosis prompted us to discover new candidate biomarkers for HCV and HCC. We used aptamer-based fractionation technology to reduce serum complexity, differentially labeled samples (six HCV and six HCC) with fluorescent dyes, and resolved proteins in pairwise two-dimensional difference gel electrophoresis. DeCyder software was used to identify differentially expressed proteins and spots picked, and MALDI-MS/MS was used to determine that ApoA1 was down-regulated by 22% (p < 0.004) in HCC relative to HCV. Differential expression quantified via two-dimensional difference gel electrophoresis was confirmed by means of 18O/16O stable isotope differential labeling with LC-MS/MS zoom scans. Technically independent confirmation was demonstrated by triple quadrupole LC-MS/MS selected reaction monitoring (SRM) assays with three peptides specific to human ApoA1 (DLATVYVDVLK, WQEEMELYR, and VSFLSALEEYTK) using 18O/16O-labeled samples and further verified with AQUA peptides as internal standards for quantification. In 50 patient samples (24 HCV and 26 HCC), all three SRM assays yielded highly similar differential expression of ApoA1 in HCC and HCV patients. These results validated the SRM assays, which were independently confirmed by Western blotting. Thus, ApoA1 is a candidate member of an SRM biomarker panel for early diagnosis, prognosis, and monitoring of HCC. Future multiplexing of SRM assays for other candidate biomarkers is envisioned to develop a biomarker panel for subsequent verification and validation studies. PMID:24008390

Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China.

PubMed

Yu, Wenzhou; Liu, Dawei; Zheng, Jingshan; Liu, Yanmin; An, Zhijie; Rodewald, Lance; Zhang, Guomin; Su, Qiru; Li, Keli; Xu, Disha; Wang, Fuzhen; Yuan, Ping; Xia, Wei; Ning, Guijun; Zheng, Hui; Chu, Yaozhu; Cui, Jian; Duan, Mengjuan; Hao, Lixin; Zhou, Yuqing; Wu, Zhenhua; Zhang, Xuan; Cui, Fuqiang; Li, Li; Wang, Huaqing

2016-04-01

China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Simultaneous determination of 13 fluoroquinolone and 22 sulfonamide residues in milk by a dual-colorimetric enzyme-linked immunosorbent assay

USDA-ARS?s Scientific Manuscript database

Enzyme-linked immunosorbent assays (ELISAs) usually focus on the detection of a single analyte or a single group of analytes, e.g., fluoroquinolones or sulfonamides. However, it is often necessary to simultaneously monitor the two classes of antimicrobial residues in different food matrices. In th...

Hepatitis B virus infection in Chinese patients with hepatitis C virus infection: prevalence, clinical characteristics, viral interactions and host genotypes: a nationwide cross-sectional study

PubMed Central

Yan, Li-Bo; Rao, Hui-Ying; Ma, Yuan-Ji; Bai, Lang; Chen, En-Qiang; Du, Ling-Yao; Yang, Rui-Feng; Wei, Lai; Tang, Hong

2016-01-01

Objectives Little is known about hepatitis B virus (HBV) infection in patients with hepatitis C virus (HCV) infection in China. This study aimed to evaluate the prevalence, clinical characteristics, viral interactions and host genotypes of HBV/HCV dual infection compared with HCV monoinfection. Study design A cross-sectional study. Setting China. Participants and methods 997 patients with HCV from 28 university-affiliated hospitals in China were enrolled in this research. Patients were divided into two subgroups. Results The prevalence of HBV infection in patients with HCV was 4.11% (41/997). The age-specific prevalence of HBsAg was 0.70%, 3.97% and 5.85% in groups aged 18–30, 30–50 and >50 years old (p=0.057), respectively. Patients with HBV/HCV dual infection and patients with HCV monoinfection had similar HCV viral loads (5.80±0.89 vs 5.83±1.00 log10 IU/mL, p=0.904). The dominant HCV genotype was 1b in both groups (53.65% vs 56.90%, p=0.493). The protective C allele in IL-28B (rs12979860) was also the dominant allele type in both patient groups (85.36% vs 83.99%, p=0.814). Patients with HBV/HCV dual infection had a higher ratio of liver cirrhosis and hepatic decompensation than patients with HCV monoinfection (39.02% vs 17.69%, p=0.001; 31.70% vs 12.13%, p=0.001). Conclusions The HBV burden was moderate in HCV-infected patients in China. Liver cirrhosis was more common in patients with HBV/HCV dual infection, suggesting the need for closer monitoring of dual-infected individuals. Trial registration number NCT01293279; Post-results. PMID:27733412

Controlled attenuation parameter is correlated with actual hepatic fat content in patients with non-alcoholic fatty liver disease with none-to-mild obesity and liver fibrosis.

PubMed

Fujimori, Naoyuki; Tanaka, Naoki; Shibata, Soichiro; Sano, Kenji; Yamazaki, Tomoo; Sekiguchi, Tomohiro; Kitabatake, Hiroyuki; Ichikawa, Yuki; Kimura, Takefumi; Komatsu, Michiharu; Umemura, Takeji; Matsumoto, Akihiro; Tanaka, Eiji

2016-09-01

Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(®) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m(2) (r = 0.579, P < 0.0001), especially less than 25 kg/m(2) (r = 0.708, P < 0.01), but the meaningful correlation disappeared in the patients with BMI of 28 kg/m(2) or more. In the patients with BMI of less than 28 kg/m(2) , CAP quantitativeness was affected by the presence of stage 2-4 fibrosis, but not the presence of hepatocyte ballooning and severity of lobular inflammation. CAP may be a promising tool for quantifying hepatic fat content in NAFLD patients with none-to-mild obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28 kg/m(2) or significant hepatic fibrosis. © 2016 The Japan Society of Hepatology.

Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

PubMed

El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

2017-09-01

To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Cold activation of complement for monitoring the response to interferon in patients with chronic hepatitis C.

PubMed

Akahane, Y; Miyazaki, Y; Naitoh, S; Takeda, K; Tsuda, F; Okamoto, H; Itoh, K; Miyakawa, Y; Mayumi, M

1996-02-01

Because of its specific association with hepatitis C virus (HCV) infection, the cold activation of complement is an easy and inexpensive indicator of HCV viremia. It was evaluated for eligibility as a marker of response to interferon in patients with hepatitis C. The cold activation of complement was determined by the loss or decrease of hemolytic activity with the microtitration method in sera that had been stored at 4 degrees C overnight. We observed the loss of hemolytic activity by the cold activation of complement in 236 (72%) and a decrease in 56 (17%) of 327 sera from patients with HCV-associated chronic liver disease, which was much more (p < 0.001) that in 1 (1%) and 13 (14%), respectively, of 49 sera from patients with chronic liver disease associated with hepatitis B virus infection. Interferon-alpha (total dose 516 x 10(6) units) or interferon-alpha 2b (774 x 10(6) units) was given to 67 patients with chronic hepatitis C, of whom 56 had the cold activation of complement. The response to interferon was evaluated by the clearance of serum HCV RNA at 6 months after the completion of therapy. The cold activation of complement disappeared in 18 patients, of whom 15 (86%) responded. It persisted or fluctuated in the remaining 38 patients, only six (16%) of whom responded to interferon (p < 0.001). The cold activation of complement once disappeared at the completion of interferon and then reappeared in patients who relapsed after completing interferon therapy. These results indicate that the cold activation of complement may be associated with the presence of HCV in blood and a lower rate of durable response after completion of interferon therapy.

Performance Characteristics of a New Consensus Commercial Kit for Hepatitis D Virus RNA Viral Load Quantification.

PubMed

Le Gal, Frédéric; Dziri, Samira; Gerber, Athenaïs; Alloui, Chakib; Ben Abdesselam, Zahia; Roulot, Dominique; Brichler, Ségolène; Gordien, Emmanuel

2017-02-01

Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure and accelerates evolution toward cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long-term administration of pegylated alpha-interferon with a sustained virological response in 30% of the patients. Very recently, new, promising anti-HDV therapies have been developed and are already being used in clinical trials. HDV RNA viral load (HDVL) monitoring must be an integral part of the management of the infected patients. However, HDV genus is characterized by a high genetic variability into eight genotypes (HDV-1 to -8), and most available in-house or commercial assays are useful for only a limited subset of genotypes. Results of a comparison of the performance of a new kit for HDVL quantification with the consensus in-house assay of the French National Reference Laboratory for HDV developed in 2005 are reported here. A total of 611 clinical samples of all HDV genotypes with various HDVL values, including several consecutive samples over several years from 36 patients, were studied. A specificity, sensitivity, and reproducibility evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and the WHO HDV RNA international standard. Overall results were strictly comparable between the two assays (median difference, 0.07 log IU/ml), with high diagnosis precision and capacity. In summary, this new kit showed high performance in detection/quantification of HDVL, regardless of the genotype of the infecting strain used, and seems to be a suitable tool for patient management. Copyright © 2017 American Society for Microbiology.

[The role of oxidative stress and arterial blood supply in the transplanted liver function].

PubMed

Kóbori, László; Sárváry, Enikö; Nemes, Balázs; Lakatos, Márta; Fehérvári, Imre; Görög, Dénes; Dallos, Gábor; Gerlei, Zsuzsa; Fazakas, János; Tóth, Tibor; Lengyel, Gabriella; Fehér, János; Járay, Jenö

2003-11-09

Reperfusion injury and hepatic artery thrombosis are major causes of graft failure after liver transplantation. The magnitude of oxidative stress increases after reperfusion and the appearance of an arterial thrombosis presents a higher risk for the graft and patient survival. The aim of the study was to detect the level of oxidative stress in the perioperative period of transplantation. Clinical documentations of 32 patients were investigated and the level of myeloperoxidase (MPO) was measured for the monitoring of the oxidative stress. The mean age of the patients was 43 years and hepatitis C cirrhosis was the most common indication (14 cases, 43%). Two retransplantations were done. In 24 cases (75%) the primary graft functions and patient survival were good. Eight patients died, in two cases because of acute liver failure, in two cases due to primary non function and in four cases due to late complications. The incidence of hepatic artery thrombosis was 11% (4 cases) and the incidence of acute rejection was 35% (12 cases). The level of MPO was higher (65 ng/ml) in all patients before operation. After the first 48 hours this level increased significantly (p < 0.0001) up to the mean level of 123 ng/ml and decreased after one week. In the cases with acute liver failure and hepatic artery thrombosis high levels of MPO were measured. This study provides evidence of increased oxidative stress before liver transplantation. The magnitude of these changes increased after operation, mostly in cases with acute liver failure and hepatic artery thrombosis. Reducing the reperfusion injury and performing an "ideal" arterial supply for the liver-graft present better survival.

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice

PubMed Central

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A.; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-ichiro; Jishage, Kou-ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression—not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for producing chimeric mice for use in future long-term studies, including hepatitis virus infection analysis or drug toxicity studies. PMID:26536627

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

PubMed

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-Ichiro; Jishage, Kou-Ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for producing chimeric mice for use in future long-term studies, including hepatitis virus infection analysis or drug toxicity studies.

Molecular characterization of hepatitis C virus for determination of subtypes and detection of resistance mutations to protease inhibitors in a group of intravenous drug users co-infected with HIV.

PubMed

Silva, Tânia; Cortes Martins, Helena; Coutinho, Rodrigo; Leitão, Emília; Silva, Rui; Pádua, Elizabeth

2015-09-01

Modifications in therapeutic regimens for the treatment of hepatitis C virus (HCV) have been observed since the approval of viral protease inhibitors (PI), and the selection of natural drug-resistant variants has been also reported. Thus, it becomes crucial to be aware of consequences of new therapeutic approaches and make available tools for monitoring the infection. The study aimed to apply an "in-house" method for amplification and sequencing of the NS3 region which is the target of PI, and allowing simultaneously the classification of viral subtypes and identification of resistance mutations. Forty-seven samples collected from HIV injecting drug users and drug naive for HCV protease inhibitors were tested for anti-HCV antibodies, 93.6% of them had a positive result and in 70.5% was determined HCV active infection. High frequency of subtype 1a (46.2%), followed by an equal proportion of subtypes 3a, 4a, and 4d (15.4%) was obtained. Two potential recombinants, RF1_2k/1b (3.8%) and 2q/2k (3.8%) were identified. Substitutions V36L/P, T54A, I72L/N/T/V, Q80K/G, S122R/T, D168Q, and I170L/V were observed in 65.4% of the samples. The T54A and Q80K mutations, and the combination V36L + T54A were also identified. Polymorphisms were observed exclusively associated with specific genotypes, particularly, I72L and D168Q with genotype 3, and S122T with genotype 4. The V36L substitution was identified in 92.8% of sequences of non-genotype 1 denoting that this amino acid substitution is a natural polymorphism associated with non-genotype 1 strains. Although no major PI resistance mutations were detected, a more extensive study is needed to evaluate the impact of mutations identified in efficacy of PI treatment. © 2015 Wiley Periodicals, Inc.

A Parallel Sliding Region Algorithm to Make Agent-Based Modeling Possible for a Large-Scale Simulation: Modeling Hepatitis C Epidemics in Canada.

PubMed

Wong, William W L; Feng, Zeny Z; Thein, Hla-Hla

2016-11-01

Agent-based models (ABMs) are computer simulation models that define interactions among agents and simulate emergent behaviors that arise from the ensemble of local decisions. ABMs have been increasingly used to examine trends in infectious disease epidemiology. However, the main limitation of ABMs is the high computational cost for a large-scale simulation. To improve the computational efficiency for large-scale ABM simulations, we built a parallelizable sliding region algorithm (SRA) for ABM and compared it to a nonparallelizable ABM. We developed a complex agent network and performed two simulations to model hepatitis C epidemics based on the real demographic data from Saskatchewan, Canada. The first simulation used the SRA that processed on each postal code subregion subsequently. The second simulation processed the entire population simultaneously. It was concluded that the parallelizable SRA showed computational time saving with comparable results in a province-wide simulation. Using the same method, SRA can be generalized for performing a country-wide simulation. Thus, this parallel algorithm enables the possibility of using ABM for large-scale simulation with limited computational resources.

Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

PubMed

Lim, C; Vibert, E; Azoulay, D; Salloum, C; Ishizawa, T; Yoshioka, R; Mise, Y; Sakamoto, Y; Aoki, T; Sugawara, Y; Hasegawa, K; Kokudo, N

2014-04-01

Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Detection of Hepatitis C core antibody by dual-affinity yeast chimera and smartphone-based electrochemical sensing.

PubMed

Aronoff-Spencer, Eliah; Venkatesh, A G; Sun, Alex; Brickner, Howard; Looney, David; Hall, Drew A

2016-12-15

Yeast cell lines were genetically engineered to display Hepatitis C virus (HCV) core antigen linked to gold binding peptide (GBP) as a dual-affinity biobrick chimera. These multifunctional yeast cells adhere to the gold sensor surface while simultaneously acting as a "renewable" capture reagent for anti-HCV core antibody. This streamlined functionalization and detection strategy removes the need for traditional purification and immobilization techniques. With this biobrick construct, both optical and electrochemical immunoassays were developed. The optical immunoassays demonstrated detection of anti-HCV core antibody down to 12.3pM concentrations while the electrochemical assay demonstrated higher binding constants and dynamic range. The electrochemical format and a custom, low-cost smartphone-based potentiostat ($20 USD) yielded comparable results to assays performed on a state-of-the-art electrochemical workstation. We propose this combination of synthetic biology and scalable, point-of-care sensing has potential to provide low-cost, cutting edge diagnostic capability for many pathogens in a variety of settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperacute Simultaneous Cardiocerebral Infarction: Rescuing the Brain or the Heart First?

PubMed

Kijpaisalratana, Naruchorn; Chutinet, Aurauma; Suwanwela, Nijasri C

2017-01-01

Concurrent acute ischemic stroke and acute myocardial infarction is an uncommon medical emergency condition. The challenge for the physicians regarding the management of this situation is paramount since early management of one condition will inevitably delay the other. We present two illustrative cases of "hyperacute simultaneous cardiocerebral infarction" who presented with simultaneous cardiocerebral infarction and arrived at the hospital within the thrombolytic therapeutic window for acute ischemic stroke of 4.5 h. We propose an algorithm for managing the patient with hyperacute simultaneous cardiocerebral infarction based on hemodynamic status and suggest close cardiac monitoring based on the site of cerebral infarction.

Audit of Potable and Nonpotable Water in Iraq

DTIC Science & Technology

2008-03-07

including hepatitis, giardiasis, and typhoid fever . Although there was no way to determine whether water provided by the contractors and military water... discovered that KBR personal hygiene facilities at Camp Q-West. KBR distributed the chlorinated wastewat rsonnel. KBR did not monitor or record the... discover resulted in KBR superchlorinating e y procedures to execute if water became unsafe. We documented three examples of potential for

Abacavir/Dolutegravir/Lamivudine (Triumeq)–Induced Liver Toxicity in a Human Immunodeficiency Virus–Infected Patient

PubMed Central

Jain, Rupali; Roxby, Alison C.

2017-01-01

Abstract Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus–infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended. PMID:28748198

Fully-automated, high-throughput micro-computed tomography analysis of body composition enables therapeutic efficacy monitoring in preclinical models.

PubMed

Wyatt, S K; Barck, K H; Kates, L; Zavala-Solorio, J; Ross, J; Kolumam, G; Sonoda, J; Carano, R A D

2015-11-01

The ability to non-invasively measure body composition in mouse models of obesity and obesity-related disorders is essential for elucidating mechanisms of metabolic regulation and monitoring the effects of novel treatments. These studies aimed to develop a fully automated, high-throughput micro-computed tomography (micro-CT)-based image analysis technique for longitudinal quantitation of adipose, non-adipose and lean tissue as well as bone and demonstrate utility for assessing the effects of two distinct treatments. An initial validation study was performed in diet-induced obesity (DIO) and control mice on a vivaCT 75 micro-CT system. Subsequently, four groups of DIO mice were imaged pre- and post-treatment with an experimental agonistic antibody specific for anti-fibroblast growth factor receptor 1 (anti-FGFR1, R1MAb1), control immunoglobulin G antibody, a known anorectic antiobesity drug (rimonabant, SR141716), or solvent control. The body composition analysis technique was then ported to a faster micro-CT system (CT120) to markedly increase throughput as well as to evaluate the use of micro-CT image intensity for hepatic lipid content in DIO and control mice. Ex vivo chemical analysis and colorimetric analysis of the liver triglycerides were performed as the standard metrics for correlation with body composition and hepatic lipid status, respectively. Micro-CT-based body composition measures correlate with ex vivo chemical analysis metrics and enable distinction between DIO and control mice. R1MAb1 and rimonabant have differing effects on body composition as assessed by micro-CT. High-throughput body composition imaging is possible using a modified CT120 system. Micro-CT also provides a non-invasive assessment of hepatic lipid content. This work describes, validates and demonstrates utility of a fully automated image analysis technique to quantify in vivo micro-CT-derived measures of adipose, non-adipose and lean tissue, as well as bone. These body composition metrics highly correlate with standard ex vivo chemical analysis and enable longitudinal evaluation of body composition and therapeutic efficacy monitoring.

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30. PMID:29201720

US EPA Base Study Standard Operating Procedure for Continuous Monitoring of Indoor Air

EPA Pesticide Factsheets

The procedure described is intended for monitoring continuously and simultaneously, at selected work sites, parameters that are most commonly associated with the quality of indoor environments: the concentrations of carbon dioxide (CO2), carbon monoxide (CO), temperature, relative humidity (RH), illumination, and noise.

Laboratory evaluation of dual-frequency multisensor capacitance probes to monitor soil water and salinity

USDA-ARS?s Scientific Manuscript database

Real-time information on salinity levels and transport of fertilizers are generally missing from soil profile knowledge bases. A dual-frequency multisensor capacitance probe (MCP) is now commercially available for sandy soils that simultaneously monitor volumetric soil water content (VWC, ') and sa...

Improving streamflow prediction using remotely-sensed soil moisture and snow depth

USDA-ARS?s Scientific Manuscript database

The monitoring of both cold and warm season hydrologic processes in headwater watersheds is critical for accurate water resource monitoring in many alpine regions. This work presents a new method that explores the simultaneous use of remotely sensed surface soil moisture (SM) and snow depth (SD) ret...

Imaging Features on Contrast-Enhanced Ultrasound and Clinical Characteristics of Hepatitis B Virus-Related Combined Hepatocellular-Cholangiocarcinoma: Comparison with Hepatitis B Virus-Related Hepatocellular Carcinoma.

PubMed

Ye, Jieyi; Xie, Xiaoyan; Liu, Baoxian; Zhang, Xiaoer; Wang, Wei; Huang, Xiaowen; Lu, Mingde; Huang, Guangliang

2017-11-01

The objective of this study was to compare the clinical characteristics and imaging features on contrast-enhanced ultrasound (CEUS) of hepatitis B virus (HBV)-related combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC). Thirty-one pathologically proven CHCs were included and 31 HCCs were randomly selected as controls. Elevated carbohydrate antigen (CA) 19-9 alone and simultaneous elevation of α-fetoprotein and CA19-9 were more frequent in CHC than in HCC patients (p = 0.004 and 0.029, respectively). On CEUS, homogeneous, heterogeneous and peripheral irregular rim-like enhancement was illustrated in 8 (25.8%), 12 (38.7%) and 11 (35.5%) CHCs and in 6 (19.4%), 23 (74.1%) and 2 (6.5%) HCCs, respectively (p = 0.007). Multivariate logistic regression analysis revealed CA19-9 elevation (p = 0.011, odds ratio [OR] = 6.545) and peripheral irregular rim-like enhancement on CEUS (p = 0.017, OR = 7.718) were independent variables. A receiver operating characteristic curve was plotted and the area under the curve was 0.740. CHC should be watched for in HBV-infected patients with liver tumor manifesting peripheral irregular rim-like enhancement on CEUS, accompanied by CA19-9 elevation. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Mediated effect of endotoxin and lead upon hepatic metabolism

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

Kuttner, R.E.; Ebata, T.; Schumer, W.

A test was made of the possibility that gram-negative bacterial cell wall lipopolysaccharides acted directly on key glucoregulatory enzymes in rat liver cytosol to cause the characteristic hypoglycemia of severe endotoxemia. Fasted male rats were sensitized to endotoxin by the simultaneous intravenous injection of lead acetate. The minimum systemic dosage of endotoxin necessary to perturb the normal pattern of hepatic glycolytic intermediates was determined by serial testing with diminishing dosages of endotoxin. The hepatocyte concentration of endotoxin was then calculated from this minimum dosage by use of literature data on the fraction of endotoxin delivered to liver cells after amore » systemic intravenous injection of radiochromium labeled lipopolysaccharides. Accepting a molecular weight of 118,000 daltons for the smallest endotoxin monomer capable of evoking a physiologic response, the molar amount of endotoxin present in 1 gram of hepatocytes was readily calculated. The concentration of glucoregulatory enzymes in parenchymal cells was then estimated from other literature sources. It was found that the amount of endotoxin in the hepatocytes was insufficient to combine directly with even 1 per cent of the quantity of a single key glucoregulatory enzyme in liver parenchyma. Since a one to one stoichiometric reaction between endotoxin and enzyme could not occur in the liver cytosol, a direct interaction mechanism between agonist and biocatalyst can be ruled out. It is concluded that bacterial endotoxin must act on hepatic glucoregulation by an indirect mechanism presumably based upon the release and operation of mediators.« less

Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization

NASA Astrophysics Data System (ADS)

Elkin, Carl D.; Zuccola, Harmon J.; Hogle, James M.; Joseph-McCarthy, Diane

2000-11-01

Hepatitis delta virus (HDV) encodes a single polypeptide called hepatitis delta antigen (DAg). Dimerization of DAg is required for viral replication. The structure of the dimerization region, residues 12 to 60, consists of an anti-parallel coiled coil [Zuccola et al., Structure, 6 (1998) 821]. Multiple Copy Simultaneous Searches (MCSS) of the hydrophobic core region formed by the bend in the helix of one monomer of this structure were carried out for many diverse functional groups. Six critical interaction sites were identified. The Protein Data Bank was searched for backbone templates to use in the subsequent design process by matching to these sites. A 14 residue helix expected to bind to the d-isomer of the target structure was selected as the template. Over 200 000 mutant sequences of this peptide were generated based on the MCSS results. A secondary structure prediction algorithm was used to screen all sequences, and in general only those that were predicted to be highly helical were retained. Approximately 100 of these 14-mers were model built as d-peptides and docked with the l-isomer of the target monomer. Based on calculated interaction energies, predicted helicity, and intrahelical salt bridge patterns, a small number of peptides were selected as the most promising candidates. The ligand design approach presented here is the computational analogue of mirror image phage display. The results have been used to characterize the interactions responsible for formation of this model anti-parallel coiled coil and to suggest potential ligands to disrupt it.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

NASA Astrophysics Data System (ADS)

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity.

PubMed

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-08

The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

PubMed Central

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-01-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity. PMID:27824075

Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis.

PubMed

Ward, Jeanine; Kanchagar, Chitra; Veksler-Lublinsky, Isana; Lee, Rosalind C; McGill, Mitchell R; Jaeschke, Hartmut; Curry, Steven C; Ambros, Victor R

2014-08-19

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

Preparation of genosensor for detection of specific DNA sequence of the hepatitis B virus

NASA Astrophysics Data System (ADS)

Honorato Castro, Ana C.; França, Erick G.; de Paula, Lucas F.; Soares, Marcia M. C. N.; Goulart, Luiz R.; Madurro, João M.; Brito-Madurro, Ana G.

2014-09-01

An electrochemical genosensor was constructed for detection of specific DNA sequence of the hepatitis B virus, based on graphite electrodes modified with poly(4-aminophenol) and incorporating a specific oligonucleotide probe. The modified electrode containing the probe was evaluated by differential pulse voltammetry, before and after incubation with the complementary oligonucleotide target. Detection was performed by monitoring oxidizable DNA bases (direct detection) or using ethidium bromide as indicator of the hybridization process (indirect detection). The device showed a detection limit for the oligonucleotide target of 2.61 nmol L-1. Indirect detection using ethidium bromide was promising in discriminating mismatches, which is a very desirable attribute for detection of disease-related point mutations. In addition, it was possible to observe differences between hybridized and non-hybridized surfaces by atomic force microscopy.

Time and number of displays impact critical signal detection in fetal heart rate tracings.

PubMed

Anderson, Brittany L; Scerbo, Mark W; Belfore, Lee A; Abuhamad, Alfred Z

2011-06-01

Interest in centralized monitoring in labor and delivery units is growing because it affords the opportunity to monitor multiple patients simultaneously. However, a long history of research on sustained attention reveals these types of monitoring tasks can be problematic. The goal of the present experiment was to examine the ability of individuals to detect critical signals in fetal heart rate (FHR) tracings in one or more displays over an extended period of time. Seventy-two participants monitored one, two, or four computer-simulated FHR tracings on a computer display for the appearance of late decelerations over a 48-minute vigil. Measures of subjective stress and workload were also obtained before and after the vigil. The results showed that detection accuracy decreased over time and also declined as the number of displays increased. The subjective reports indicated that participants found the task to be stressful and mentally demanding, effortful, and frustrating. The results suggest that centralized monitoring that allows many patients to be monitored simultaneously may impose a detrimental attentional burden on the observer. Furthermore, this seemingly benign task may impose an additional source of stress and mental workload above what is commonly found in labor and delivery units. © Thieme Medical Publishers.

An internet-based wearable watch-over system for elderly and disabled utilizing EMG and accelerometer.

PubMed

Kishimoto, M; Yoshida, T; Hayasaka, T; Mori, D; Imai, Y; Matsuki, N; Ishikawa, T; Yamaguchi, T

2009-01-01

An effective way for preventing injuries and diseases among the elderly is to monitor their daily lives. In this regard, we propose the use of a "Hyper Hospital Network", which is an information support system for elderly people and patients. In the current study, we developed a wearable system for monitoring electromyography (EMG) and acceleration using the Hyper Hospital Network plan. The current system is an upgraded version of our previous system for gait analysis (Yoshida et al. [13], Telemedicine and e-Health 13 703-714), and lets us monitor decreases in exercise and the presence of a hemiplegic gait more accurately. To clarify the capabilities and reliability of the system, we performed three experimental evaluations: one to verify the performance of the wearable system, a second to detect a hemiplegic gait, and a third to monitor EMG and accelerations simultaneously. Our system successfully detected a lack of exercise by monitoring the iEMG in healthy volunteers. Moreover, by using EMG and acceleration signals simultaneously, the reliability of the Hampering Index (HI) for detecting hemiplegia walking was improved significantly. The present study provides useful knowledge for the development of a wearable computer designed to monitor the physical conditions of older persons and patients.

A smart health monitoring chair for nonintrusive measurement of biological signals.

PubMed

Baek, Hyun Jae; Chung, Gih Sung; Kim, Ko Keun; Park, Kwang Suk

2012-01-01

We developed nonintrusive methods for simultaneous electrocardiogram, photoplethysmogram, and ballistocardiogram measurements that do not require direct contact between instruments and bare skin. These methods were applied to the design of a diagnostic chair for unconstrained heart rate and blood pressure monitoring purposes. Our methods were operationalized through capacitively coupled electrodes installed in the chair back that include high-input impedance amplifiers, and conductive textiles installed in the seat for capacitive driven-right-leg circuit configuration that is capable of recording electrocardiogram information through clothing. Photoplethysmograms were measured through clothing using seat mounted sensors with specially designed amplifier circuits that vary in light intensity according to clothing type. Ballistocardiograms were recorded using a film type transducer material, polyvinylidenefluoride (PVDF), which was installed beneath the seat cover. By simultaneously measuring signals, beat-to-beat heart rates could be monitored even when electrocardiograms were not recorded due to movement artifacts. Beat-to-beat blood pressure was also monitored using unconstrained measurements of pulse arrival time and other physiological parameters, and our experimental results indicated that the estimated blood pressure tended to coincide with actual blood pressure measurements. This study demonstrates the feasibility of our method and device for biological signal monitoring through clothing for unconstrained long-term daily health monitoring that does not require user awareness and is not limited by physical activity.

Cost-effectiveness of rapid HCV testing and simultaneous rapid HCV and HIV testing in substance abuse treatment programs

PubMed Central

Schackman, Bruce R.; Leff, Jared A.; Barter, Devra M.; DiLorenzo, Madeline A.; Feaster, Daniel J.; Metsch, Lisa R.; Freedberg, Kenneth A.; Linas, Benjamin P.

2014-01-01

Aims To evaluate the cost-effectiveness of rapid hepatitis C virus (HCV) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs. Design We used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer, off-site HCV testing referral, on-site rapid HCV testing offer, and on-site rapid HCV and HIV testing offer. Base case inputs included 11% undetected chronic HCV, 0.4% undetected HIV, 35% HCV co-infection among HIV-infected, 53% linked to HCV care after testing antibody positive, and 67% linked to HIV care. Disease outcomes were estimated from established computer simulation models of HCV (HEP-CE) and HIV (CEPAC). Setting and Participants Data on test acceptance and costs were from a national randomized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the USA. Measurements Lifetime costs (2011 US dollars) and quality-adjusted life years (QALYs) discounted at 3% annually; incremental cost-effectiveness ratios (ICERs) Findings On-site rapid HCV testing had an ICER of $18,300/QALY compared with no testing, and was more efficient than (dominated) off-site HCV testing referral. On-site rapid HCV and HIV testing had an ICER of $64,500/QALY compared with on-site rapid HCV testing alone. In one and two-way sensitivity analyses, the ICER of on-site rapid HCV and HIV testing remained <$100,000/QALY, except when undetected HIV prevalence was <0.1% or when we assumed frequent HIV testing elsewhere. The ICER remained <$100,000/QALY in approximately 90% of probabilistic sensitivity analyses. Conclusions On-site rapid hepatitis C virus and HIV testing in substance abuse treatment programs is cost-effective at a <$100,000/ quality-adjusted life years threshold. PMID:25291977

A one-step duplex rRT-PCR assay for the simultaneous detection of duck hepatitis A virus genotypes 1 and 3.

PubMed

Hu, Qin; Zhu, Dekang; Ma, Guangpeng; Cheng, Anchun; Wang, Mingshu; Chen, Shun; Jia, Renyong; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue

2016-10-01

Duck hepatitis A virus (DHAV) is a highly infectious pathogen that causes significant bleeding lesions in the viscera of ducklings less than 3 weeks old. There are three serotypes of DHAV: serotype 1 (DHAV-1), serotype 2 (DHAV-2) and serotype 3 (DHAV-3). These serotypes have no cross-antigenicity with each other. To establish an rRT-PCR assay for the rapid detection of a mixed infection of DHAV-1 and DHAV-3, two pairs of primers and a pair of matching TaqMan probes were designed based on conserved regions of DHAV-1 VP0 and DHAV-3 VP3. Finally, we established a one-step duplex rRT-PCR assay with high specificity and sensitivity for the simultaneous detection of DHAV-1 and DHAV-3. This method showed no cross-antigenicity with the other pathogens tested, including duck plague virus, Muscovy duck parvovirus, Riemerella anatipestifer, and pathogenic E. coli from ducks. Sensitivity tests identified the minimum detection limits of this method as 98 (DHAV-1) and 10 (DHAV-3) copies/reaction. To validate the method, thirty-eight clinical samples and thirty artificially infected samples collected from dead duck embryos were studied. Thirty-seven samples were positive for DHAV-1, seventeen samples were positive for DHAV-3, and fourteen samples were positive for a mixed infection using the duplex rRT-PCR method. The method established in this study is specific, sensitive, convenient and timesaving and is a powerful tool for detecting DHAV-1, DHAV-3, and their mixed infection and for conducting surveys of pandemic virus strains. Copyright © 2016. Published by Elsevier B.V.

Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

PubMed

Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

2018-05-01

Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.