Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered

Status update on GPS integrity failure modes and effects analysis

GPS integrity anomalies have long been of great concern to the civil and military GPS communities for safety-of- life operations. The FAA, USCG, and their international counterparts have focused on how to accomplish integrity monitoring for safety-of-life services through the use of receiver autonomous integrity monitoring (RAIM), widearea and local-area augmentation systems such as WAAS and LAAS, maritime differential GPS (DGPS) and nationwide differential GPS (NDGPS). The military is preparing to certify PPS RAIM receivers and is in the process of developing the Joint Precision Approach and Landing System (JPALS). Integrity failure modes need to be understood in order to develop a proper monitoring capability. The main objectives of the GPS Integrity Failure Modes and Effects Analysis (IFMEA) project are to identify GPS integrity monitoring requirements, examine GPS failure data in order to identify integrity failure modes, examine the causes and effects of the failures, as well as their probability of occurrence, determine the impact of integrity anomalies on users, and recommend preventive actions. The IFMEA project is focused on integrity anomalies that are due to hardware and software failures in the satellite vehicles (SVs) and Operational Control System (OCS). This paper provides a status update on the GPS IFMEA effort which is jointly funded by the Interagency GPS Executive Board (IGEB), the GPS Joint Program Office (JPO), and the Federal Aviation Administration (FAA). The IFMEA project began in 2002 under IGEB stewardship funding. Through the IFMEA project, Aberration Characterization Sheets (ACS) have been developed and updated for all GPS satellites through the Block IIR generation and work is now beginning on Block IIR-M, IIF, and the Architecture Evolution Plan (AEP) for the OCS. There is a need by those in the user community who are developing safety of life systems to be able to easily research GPS integrity anomaly data. In support of this effort, the IFMEA team is developing a database of all GPS service anomalies that can be accessed by type of anomaly, satellite number, satellite block affected, magnitude of error, date of occurrence, and duration of event. An effects analysis for WAAS and LAAS is being conducted to determine the impact on these augmentation systems from integrity anomalies. Finally, the IFMEA project is evaluating signal quality monitoring (SQM) algorithms to ensure proper detection of integrity anomalies and identify any design constraints or modifications to the GPS SV and OCS to either prevent failures that degrade integrity or provide protection from any adverse operational impact. This work is referenced in other ION papers [1] and [2]. The benefits of this work are to gain a better understanding of integrity anomalies, their probability of occurrence, and how to monitor for them. This information is essential to the design of differential GPS networks to support safety of life operations and will assist in meeting international commitments to describe GPS performance. The work performed under this study also will provide a technical basis to update the SPS and PPS Performance Standards and help develop recommendations for improvements to future GPS satellites and the operational control system

Promjene citokroma P450 jetre i mozga nakon višekratne primjene kokaina, samog ili u kombinaciji s nifedipinom

The objective of this study was to evaluate possible changes caused by multiple cocaine administration, alone and in combination with 1,4-dihydropiridine calcium channel blocker nifedipine, on cytochrome P450 levels both in the brain and liver. The experiment was done on male Wistar rats divided in four groups: control, treated with nifedipine (5 mg kg-1 i.p. for five days), treated with cocaine (15 mg kg-1 i.p. for five days), and treated with nifedipine and 30 minutes later with cocaine (also for five days). Total cytochrome P450 was measured spectrometrically in liver and brain microsomes. Multiple administration of cocaine alone and in combination with nifedipine did not change the brain P450 significantly. In the liver, nifedipine significantly increased P450 by 28 % vs. control. In contrast, cocaine significantly decreased P450 by 17 % vs. control. In animals treated with nifedipine and cocaine, cytochrome P450 increased 11 % (p<0.01) vs. control, decreased 12.5 % (p<0.001) vs. nifedipine group and increased 34 % (p<0.0001) vs. cocaine group. These results suggest that the cocaine and nifedipine interact at the metabolic level.Cilj je ovog istraživanja bio ocijeniti moguće promjene uzrokovane višestrukom primjenom kokaina kao jedinog agensa odnosno u kombinaciji s nifedipinom, 1,4-dihidropiridinskim blokatorom kalcijevih kanala, na razine citokroma P450 u mozgu i jetri štakora. Životinje (mužjaci Wistar štakora) podijeljene su u četiri skupine: kontrolnu skupinu, skupinu koja je primala nifedipin (5 mg kg-1 ip. pet dana), skupinu koja je primala kokain (15 mg kg-1 ip. pet dana) i skupinu koja je primala nifedipin te pola sata kasnije kokain (također pet dana). Ukupna količina citokroma P450 mjerena je spektrofotometrijski u mikrosomima jetre i mozga. Višestruka primjena samo kokaina odnosno u kombinaciji s nifedipinom nije značajno promijenila razine citokroma P450 u mozgu. U jetri je međutim nifedipin u odnosu na kontrolnu skupinu uzrokovao povišenje razina P450, za statistički značajnih 28 %. Kokain je uzrokovao statistički značajan pad razine P450 za 17 % u odnosu na kontrolnu skupinu. U životinja koje su primale kombinaciju nifedipina i kokaina razina citokroma P450 narasla je za 11 % (p<0.01) u odnosu na kontrolu, bila je 12.5 % (p<0.001) niža u odnosu na skupinu koja je primala nifedipin te viša za 34 % (p<0.0001) u odnosu na skupinu koja je primala samo kokain. Rezultati ovog istraživanja upućuju na interakcije ovih spojeva koje se odvijaju na razini metabolizm

Forty years literature review of primary lung lymphoma

There are several unresolved issues through out the literature regarding the entity of primary lung lymphoma. Extensive literature review of this uncommon pathology is carried out

EFFECTS OF INVIVO BENZENE TREATMENT ON CYTOCHROME-P450 AND MIXED-FUNCTION OXIDASE ACTIVITIES OF GILTHEAD SEABREAM (SPARUS-AURATA) LIVER-MICROSOMES

1. Treatment of gilthead seabream (Sparus aurata) with benzene 0.6 ml/kg/day, s.c., for four consecutive days resulted in a marked 78% and 73% decrease in total cytochrome P450 content and 7-ethoxyresorufin O-deethylase activity of liver microsomes, respectively

IN-VIVO EFFECTS OF THE ANESTHETIC, BENZOCAINE, ON LIVER MICROSOMAL CYTOCHROME-P450 AND MIXED-FUNCTION OXIDASE ACTIVITIES OF GILTHEAD SEABREAM (SPARUS-AURATA)

Gilthead seabreams were exposed to benzocaine, 4-aminobenzoic acid ethyl ester, 57 mg/l in sea water for 3 min, daily, for 2 or 3 consecutive days. The fish were killed 20 hr after the last treatment. Benzocaine treatment for 2 or 3 days resulted in 57% and 67% inhibition of liver microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase activities, respectively. The total cytochrome P450 content of fish liver microsomes was unaltered following the 2-day benzocaine treatment. However, additional 3 min benzocaine treatment on day 3 reduced cytochrome P450 level by 50%. Benzocaine produced type II difference spectra with rabbit liver microsomes. Difference spectra of fish liver microsomes elicited by benzocaine were complex. The position of peak and intensity were greatly influenced by the concentration of benzocaine

Separation of three P450 isozymes from liver microsomes of gilthead seabream treated with D-NF and partial purification of cytochrome P4501A1

Three distinct cytochrome P450 isozymes, P4501A1, P4502B and an unidentified P450 isozyme were separated and isolated from beta-NF-treated gilthead seabream liver microsomes. Cytochrome P4501A1 was partially purified from beta-NF-treated gilthead seabream liver microsomes in the presence of detergents Emulgen 913 and cholate and protease inhibitors using two DEAE-cellulose, Porapak Q and two hydroxylapatite column chromatographies. The overall yield of purified P4501A1 was 1.2% with respect to microsomal total P450 with a specific content of 3 nmol/mg protein. The purified P4501A1 was characterized with respect to spectral, electrophoretic, biocatalytic and immunochemical properties, which are found to be similar to P4501A1s purified from other teleost species such as trout, scup, cod and perch suggesting that the P450 we have purified belongs to CYP1A1

Inhibitory effects of divalent metal ions on liver microsomal 7-ethoxyresorufin O-deethylase (EROD) activity of leaping mullet

The purpose of the present study was to elucidate in vitro effects of Hg2+, Zn2+, Ni2+ and Cd2+ on cytochrome P4501Al (CYP1A1) dependent EROD activities in leaping mullet liver microsomes. Fish captured from the most polluted part of Izmir Bay, had highly elevated EROD activities, and induced CYP1A1 protein levels as determined by Western blotting. Although all of the metal ions caused inhibition of the initial velocity of the reaction, Hg2+ and Cd2+ exhibited much higher inhibitory effect at lower concentrations and they were evidently more potent inhibitors than others. The inhibitor concentration giving 50% inhibition (IC50 values) of Zn2+, Ni2+, Cd2+ and Hg2+ of initial EROD activity were 107, 16, 1.3 and 0.15 micromolar, respectively. Glutathione (GSH) at 0.5 mM final concentration, completely reversed Ni2+ and Cd2+ inhibition of EROD activity indicating the protective action of GSH