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https://www.readbyqxmd.com/read/28335386/revisiting-the-metabolism-and-bioactivation-of-ketoconazole-in-human-and-mouse-using-liquid-chromatography-mass-spectrometry-based-metabolomics
#1
Ju-Hyun Kim, Won-Gu Choi, Sangkyu Lee, Hye Suk Lee
Although ketoconazole (KCZ) has been used worldwide for 30 years, its metabolic characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its therapeutic use. In this study, we used liquid chromatography-mass spectrometry-based metabolomics to evaluate the metabolic profile of KCZ in mouse and human and identify the mechanisms underlying its hepatotoxicity. A total of 28 metabolites of KCZ, 11 of which were novel, were identified in this study. Newly identified metabolites were classified into three categories according to the metabolic positions of a piperazine ring, imidazole ring, and N-acetyl moiety...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335271/distribution-of-iron-oxide-core-titanium-dioxide-shell-nanoparticles-in-vx2-tumor-bearing-rabbits-introduced-by-two-different-delivery-modalities
#2
Tamer Refaat, Derek West, Samar El Achy, Vamsi Parimi, Jasmine May, Lun Xin, Kathleen R Harris, William Liu, Michael Beau Wanzer, Lydia Finney, Evan Maxey, Stefan Vogt, Reed A Omary, Daniele Procissi, Andrew C Larson, Tatjana Paunesku, Gayle E Woloschak
This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests...
August 3, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334008/low-sphingosine-1-phosphate-plasma-levels-are-predictive-for-increased-mortality-in-patients-with-liver-cirrhosis
#3
Susen Becker, Benedict Kinny-Köster, Michael Bartels, Markus Scholz, Daniel Seehofer, Thomas Berg, Cornelius Engelmann, Joachim Thiery, Uta Ceglarek, Thorsten Kaiser
BACKGROUND & AIM: The association of circulating sphingosine-1-phosphate (S1P), a bioactive lipid involved in various cellular processes, and related metabolites such as sphinganine-1-phosphate (SA1P) and sphingosine (SPH) with mortality in patients with end-stage liver disease is investigated in the presented study. S1P as a bioactive lipid mediator, is involved in several cellular processes, however, in end-stage liver disease its role is not understood. METHODS: The study cohort consisted of 95 patients with end-stage liver disease and available information on one-year outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#4
Li Q Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P Heruth, Charlie Bi, Roger Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt(-/-)) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332829/impact-of-peg-chain-length-on-the-physical-properties-and-bioactivity-of-pegylated-chitosan-sirna-nanoparticles-in-vitro-and-in-vivo
#5
Chuanxu Yang, Shan Gao, Frederik Dagnaes-Hansen, Maria Jakobsen, Jørgen Kjems
PEGylation of cationic polyplexes is a promising approach to enhance the stability and reduce unspecific interaction with biological components. Herein, we systematically investigate the impact of PEGylation on physical and biological properties of chitosan/siRNA polyplexes. A series of chitosan-PEG copolymers (CS-PEG2k, CS-PEG5k and CS-PEG10k) were synthesized with similar PEG mass content but with different molecular weight. PEGylation with higher molecular weight and less grafting degree resulted in smaller and more compacted nanoparticles with relatively higher surface charge...
March 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28331967/decreased-basal-hepatic-glucose-uptake-in-impaired-fasting-glucose
#6
Mariam Alatrach, Christina Agyin, John Adams, Ralph A DeFronzo, Muhammad A Abdul-Ghani
AIMS/HYPOTHESIS: This research aimed to define the pathophysiological defects responsible for the elevated fasting plasma glucose (FPG) concentration and excessive rise in post-load plasma glucose observed in individuals with impaired fasting glucose (IFG). METHODS: We used tracer techniques to quantify basal splanchnic (primarily hepatic) glucose uptake and glucose fluxes following glucose ingestion in individuals with normal glucose tolerance (NGT; n = 10) and IFG (n = 10)...
March 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28331565/evaluation-of-prognostic-factors-effect-on-survival-time-in-patients-with-colorectal-cancer-based-on-weibull-competing-risks-model
#7
Soraya Moamer, Ahmadreza Baghestani, Mohamad Amin Pourhoseingholi, Nastaran Hajizadeh, Farzaneh Ahmadi, Mohsen Norouzinia
AIM: The aim of this study was to assess the association between survival of patients with colorectal cancer and prognostic factors in a competing risk parametric model using Weibull distribution. BACKGROUND: The prognosis of colorectal cancer is relatively good in terms of survival time. In many prognostic studies, patients may be exposed to several types of competing events. These different causes of death are called competing risks. METHODS: Data was recorded from 372 patients with colorectal cancer who registered in the Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences (Tehran, Iran) from 2004 to 2015 in a retrospective study...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331563/%C3%A2-evaluation-of-serum-hbv-viral-load-transaminases-and-histological-features-in-chronic-hbeag-negative-hepatitis-b-patients
#8
Abbas Esmaeelzadeh, Hassan Saadatnia, Bahram Memar, Elham Mokhtari Amirmajdi, Azita Ganji, Ladan Goshayeshi, Zahra Meshkat, Alireza Pasdar, Hassan Vosoughinia, Mohammadreza Farzanehfar, Shahrzad Tehranian, Kamran Ghaffarzadehgan, Farnood Rajabzadeh, Mitra Ahadi
AIM: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). BACKGROUND: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. METHODS: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331131/the-aggressive-clinical-courses-of-hodgkin-lymphoma-primarily-diagnosed-as-methotrexate-induced-non-specific-lymphoproliferative-disorder-in-patients-with-rheumatoid-arthritis
#9
Michihide Tokuhira, Takayuki Tabayashi, Yuka Tanaka, Yasuyuki Takahashi, Yuta Kimura, Tatsuki Tomikawa, Tomoe Anan-Nemoto, Shuju Momose, Morihiro Higashi, Ayumi Okuyama, Reiko Watanabe, Koichi Amano, Jun-Ichi Tamaru, Masahiro Kizaki
Recently, attention has been focused on methotrexate-induced lymphoproliferative disease (MTX-LPD), and atypical phenotypes are occasionally documented. We encountered two patients with rheumatoid arthritis (RA) who were diagnosed with non-specific LPD (LPD-nos). Biopsy samples were not obtained during the initial examination when the LPD development was discovered, and the patients achieved a complete response after MTX cessation (case 1) or steroid pulse therapy (case 2). However, the tumors flared up 1.5 years later, and LPD-nos was determined following biopsies of the lymph node (LN, case 1) and liver (case 2)...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28331027/malignant-hypercalcaemia-related-to-parathyroid-hormone-related-peptide-pthrp-secretion-from-a-metastatic-pancreatic-neuroendocrine-tumour-net
#10
Megan Symington, Louise Davies, Gregory Kaltsas, Martin O Weickert
A 54-year-old woman presented to our centre with acute abdominal pain and vomiting. Routine blood tests showed severe hypercalcaemia (>4 mmol/L). Serum parathyroid hormone (PTH) was suppressed. CT scan detected a pancreatic mass and some liver lesions, initially suspicious for metastatic pancreatic adenocarcinoma. Liver biopsy however revealed the presence of a well-differentiated, grade 1, metastatic neuroendocrine tumour (NET) where prognosis is considerably better. Serum PTHrP was raised, indicating paraneoplastic hypercalcaemia, most likely secondary to the pancreatic NET...
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28331026/aberrant-non-neoplastic-liver-tissue-presenting-as-an-intra-atrial-mass
#11
Benjamin Peake, Siven Seevanayagam, Melisa Vazquez, Laurence Weinberg
No abstract text is available yet for this article.
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28330992/localized-hepatic-lobular-regeneration-by-central-vein-associated-lineage-restricted-progenitors
#12
Jonathan M Tsai, Pang Wei Koh, Ania Stefanska, Liujing Xing, Graham G Walmsley, Nicolas Poux, Irving L Weissman, Yuval Rinkevich
The regeneration of organ morphology and function following tissue loss is critical to restore normal physiology, yet few cases are documented in mammalian postnatal life. Partial hepatectomy of the adult mammalian liver activates compensatory hepatocyte hypertrophy and cell division across remaining lobes, resulting in restitution of organ mass but with permanent alteration of architecture. Here, we identify a time window in early postnatal life wherein partial amputation culminates in a localized regeneration instead of global hypertrophy and proliferation...
March 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330662/pericardial-but-not-hepatic-fat-by-ct-is-associated-with-cv-outcomes-and%C3%A2-structure-the-multi-ethnic-study-of-atherosclerosis
#13
Ravi V Shah, Amanda Anderson, Jingzhong Ding, Matthew Budoff, Oliver Rider, Steffen E Petersen, Majken Karoline Jensen, Manja Koch, Matthew Allison, Nadine Kawel-Boehm, Jessica Wisocky, Michael Jerosch-Herold, Kenneth Mukamal, Joao A C Lima, Venkatesh L Murthy
OBJECTIVES: The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity. BACKGROUND: The impact of pericardial fat-a local fat depot encasing the heart-on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate. METHODS: We studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat)...
March 10, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28328034/extraction-efficiency-and-implications-for-absolute-quantitation-of-propranolol-in-mouse-brain-liver-and-kidney-tissue-sections-using-droplet-based-liquid-microjunction-surface-sampling-high-performance-liquid-chromatography-electrospray-ionization-tandem-mass
#14
Vilmos Kertesz, Taylor M Weiskittel, Marissa Vavrek, Carol Freddo, Gary J Van Berkel
RATIONALE: Currently, the absolute quantitation aspects of droplet-based surface sampling for tissue analysis using a fully automated autosampler/high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) system have not been fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from tissue sections. METHODS: Adjacent tissue sections of propranolol-dosed mouse brain (10-μm-thick), kidney (10-μm-thick) and liver (8-, 10-, 16- and 24-μm-thick) were obtained...
July 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28327291/solid-pseudopapillary-neoplasm-of-the-pancreas-a-clinicopathological-review-of-20-cases-including-rare-examples
#15
Ayca Ersen, Anil Aysal Agalar, Erdener Ozer, Cihan Agalar, Tarkan Unek, Tufan Egeli, Mucahit Ozbilgin, Ibrahim Astarcioglu, Mustafa Olguner, Funda Obuz, Ozgul Sagol
AIMS: Solid-pseudopapillary neoplasm (SPN) is an uncommon malignant tumor of the pancreas with a favorable prognosis unlike other pancreatic neoplasms. We investigated the clinicopathological features of 20 patients with SPN in details. METHODS: The patients diagnosed as SPN in Dokuz Eylul University Hospital between January 2005 and March 2016 were reviewed in terms of clinical and histopathological data. RESULTS: Mean age of the patients was 33...
November 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28327129/short-term-overfeeding-of-zebrafish-with-normal-or-high-fat-diet-as-a-model-for-the-development-of-metabolically-healthy-versus-unhealthy-obesity
#16
Kathrin Landgraf, Susanne Schuster, Andrej Meusel, Antje Garten, Thomas Riemer, Dorit Schleinitz, Wieland Kiess, Antje Körner
BACKGROUND: Obese individuals differ in their risk of developing metabolic and cardiovascular complications depending on fat distribution (subcutaneous versus visceral) and adipose tissue (AT) phenotype (hyperplasic versus hypertrophic). However, the exact mechanisms which determine whether an obese individual is metabolically healthy or unhealthy are not clear, and analyses of the underlying pathomechanisms are limited by the lack of suitable in vivo models in which metabolically healthy versus metabolically unhealthy AT accumulation can be specifically induced...
March 21, 2017: BMC Physiology
https://www.readbyqxmd.com/read/28326452/methyleugenol-dna-adducts-in-human-liver-are-associated-with-sult1a1-copy-number-variations-and-expression-levels
#17
Roman Tremmel, Kristin Herrmann, Wolfram Engst, Walter Meinl, Kathrin Klein, Hansruedi Glatt, Ulrich M Zanger
Methyleugenol is a rodent hepatocarcinogen occurring in many herbs and spices as well as essential oils used for flavoring. Following metabolic activation by cytochromes P450 (CYPs) and sulfotransferases (SULTs), methyleugenol can form DNA adducts. Previously, we showed that DNA adduct formation by methyleugenol in mouse liver is dependent on SULT1A1 expression and that methyleugenol DNA adducts are abundant in human liver specimens. In humans, SULT1A1 activity is affected by genetic polymorphisms, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28324156/molecular-characterization-of-two-rhesus-glycoproteins-from-the-euryhaline-freshwater-white-rimmed-stingray-himantura-signifer-and-changes-in-their-transcript-levels-and-protein-abundance-in-the-gills-kidney-and-liver-during-brackish-water-acclimation
#18
Cheng T Yeam, You R Chng, Jasmine L Y Ong, Wai P Wong, Shit F Chew, Yuen K Ip
Himantura signifer is a freshwater stingray which inhabits rivers in Southeast Asia. It is ammonotelic in fresh water, but retains the capacities of urea synthesis and ureosmotic osmoregulation to survive in brackish water. This study aimed to elucidate the roles of Rhesus glycoproteins (Rhgp), which are known to transport ammonia, in conserving nitrogen (N) in H. signifer during brackish water acclimation when N became limited resulting from increased hepatic urea synthesis. The complete coding sequence of rhbg from H...
March 21, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28324016/cardiorespiratory-fitness-and-adiposity-as-determinants-of-metabolic-health-pooled-analysis-of-two-twin-cohorts
#19
Sakari Jukarainen, René Holst, Christine Dalgård, Päivi Piirilä, Jesper Lundbom, Antti Hakkarainen, Nina Lundbom, Aila Rissanen, Jaakko Kaprio, Kirsten Ohm Kyvik, Thorkild I A Sørensen, Kirsi H Pietiläinen
Context: The joint effects of cardiorespiratory fitness and body composition on metabolic health are not well known. Objective: To examine the associations of cardiorespiratory fitness (CRF), fat free mass index (FFMI) and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences. Design, setting & participants: Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n=996 and n=309)...
January 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323986/chronic-intranasal-insulin-does-not-affect-hepatic-lipids-but-lowers-circulating-bcaas-in-healthy-male-subjects
#20
Thomas Scherer, Peter Wolf, Sabina Smajis, Melania Gaggini, Martina Hackl, Amalia Gastaldelli, Peter Klimek, Elisa Einwallner, Rodrig Marculescu, Anton Luger, Clemens Fürnsinn, Siegfried Trattnig, Christoph Buettner, Martin Krššák, Michael Krebs
Context: Non-alcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Objective: Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans...
January 16, 2017: Journal of Clinical Endocrinology and Metabolism
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