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Drug induced liver dysfunction

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https://www.readbyqxmd.com/read/28688898/liver-biopsy-findings-in-patients-with-hematopoietic-cell-transplantation
#1
Farzan Eskandari, Daniel Rowan, Parameswaran Hari, Jonathan Kapke, Robert Schneidewend, Catherine Hagen, Kiyoko Oshima
Liver dysfunction is a frequent complication after hematopoietic-cell transplantation (HCT). Liver biopsy has an important role for confirming the diagnosis of graft versus host disease (GVHD) or other liver diseases. The histological features of GVHD are not specific, and GVHD and other coexisting diseases may be present in the same biopsy, which makes the histologic interpretation of the liver biopsy more complex and challenging. The aim of the study is to improve the present diagnostic criteria. 52 liver biopsies were studied...
July 5, 2017: Human Pathology
https://www.readbyqxmd.com/read/28675791/olprinone-protects-liver-from-ischemia-reperfusion-injury-through-oxidative-stress-prevention-and-protein-kinase-akt-activation
#2
Mohamed Bejaoui, Mohamed Amine Zaouali, Rim Sakly, Hassen Ben Abdennebi
Liver ischemia reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary non function after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to one hour of partial warm ischemia (70%) followed by six hours of reperfusion...
July 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28675360/four-years-of-hepatic-transplantation-in-the-republic-of-moldova
#3
Vladimir Hotineanu, Adrian Hotineanu, Serghei Burgoci, Grigore Ivancov, Natalia Taran, Angela Peltec, Dumitru Cazacu, Vitalie Sîrghi
Ever since the first liver transplant in the Republic of Moldova in 2013 we have performed 30 liver transplantations, the first having been performed in collaboration with the surgical team from Romania, led by Professor Irinel Popescu. The serious deficit of available cadaveric organs has forced us to begin with right hemi-liver transplantation from a living donor. In one third of liver transplantations we used right hemi-liver graft from a living donor, and in 2/3 of cases whole liver graft was harvested from brain-dead donors...
May 2017: Chirurgia
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#4
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28655097/-efficacy-of-combination-of-atra-ato-and-anthracyclines-induction-therapy-in-patients-with-acute-promyelocytic-leukemia
#5
R J Ma, Z M Zhu, X L Yuan, L Jiang, S W Yang, J Yang, J M Guo, L Zhang, P C Lei, Z Wang, Y Z Zang, Y Q Chen, T B Wang, D Kong, K Sun, Y Zhang
Objective: To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL). Methods: Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m(-2)·d(-1), d(1-28)) + ATO (0.16 mg·kg(-1)·d(-1), d(1-28)) + Idarubicin (8 mg·m(-2)·d(-1), d(3-5)) /daunorubicin (40 mg·m(-2)·d(-1), d(3-5)) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#6
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#7
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28629341/protective-effects-of-cynara-scolymus-leaves-extract-on-metabolic-disorders-and-oxidative-stress-in-alloxan-diabetic-rats
#8
Maryem Ben Salem, Rihab Ben Abdallah Kolsi, Raouia Dhouibi, Kamilia Ksouda, Slim Charfi, Mahdi Yaich, Serria Hammami, Zouheir Sahnoun, Khaled Mounir Zeghal, Kamel Jamoussi, Hanen Affes
BACKGROUND: Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats...
June 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#9
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28612667/all-that-glitters-yellow-is-not-gold-presentation-and-pathophysiology-of-bile-cast-nephropathy
#10
Mitchell Pitlick, Prerna Rastogi
BACKGROUND: Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#11
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16(Ink4a)-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28570676/shaofu-zhuyu-decoction-ameliorates-obesity-mediated-hepatic-steatosis-and-systemic-inflammation-by-regulating-metabolic-pathways
#12
Moonju Hong, Jeeyoun Jung, Hee-Sook Park, So Min Lee, Nam-Joo Jeong, Soon-Hee Kim, Kyoung-Won Lee, Ju-A Lee, Myung-Sunny Kim
Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang), a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS). Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD) for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28566572/importance-of-reverse-translational-research-rtr
#13
Yuichi Sugiyama
 When events lead to clinical problems, the mechanisms involved often remain unclear. This is true for medications and therapies, in addition to problems inherent in an underlying disease. However, the recent development of modeling and metric methods makes it possible to estimate the relationship between side effects and various factors to explain inter-individual differences, such as genetic polymorphisms, co-administered drugs, age, gender, dysfunction of the liver/kidney based upon the database for side effects [such as Food and Drug Administration-Adverse Event Reporting System (FDA-AERS)] and the database in a patient's medical records...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28564489/graphene-oxide-ag-nanoparticles-cooperated-with-simvastatin-as-a-high-sensitive-x-ray-computed-tomography-imaging-agent-for-diagnosis-of-renal-dysfunctions
#14
Zhan Li, Longlong Tian, Jianli Liu, Wei Qi, Qiang Wu, Haijing Wang, Mohammad Chand Ali, Wangsuo Wu, Hongdeng Qiu
Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast-enhanced computed tomography (CT) is proposed. In order to serve as contrast-enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X-ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs...
May 31, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28558354/anthocyanin-rich-riceberry-bran-extract-attenuates-gentamicin-induced-hepatotoxicity-by-reducing-oxidative-stress-inflammation-and-apoptosis-in-rats
#15
Phatchawan Arjinajarn, Nuttawud Chueakula, Anchalee Pongchaidecha, Krit Jaikumkao, Varanuj Chatsudthipong, Sugunya Mahatheeranont, Orranuch Norkaew, Nipon Chattipakorn, Anusorn Lungkaphin
Liver plays an important role in the detoxification and metabolic elimination of various drugs and harmful substances. The damaging effects on the liver tissue treated with gentamicin are multi-factorial and their mechanisms remain unclear. This study aimed to investigate the possible protective effects of anthocyanin-rich Riceberry bran extract on gentamicin-induced hepatotoxicity in rats. Riceberry bran extract was given by oral administration 30min before gentamicin injection for 15 consecutive days. Serum levels of liver marker enzymes, AST and ALT, were significantly elevated and the total serum protein level was markedly reduced in gentamicin-treated rats...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28555165/tissue-hypoperfusion-hypercoagulopathy-and-kidney-and-liver-dysfunction-after-ingestion-of-a-naphazoline-containing-antiseptic
#16
Yuko Ono, Nozomi Ono, Kazuaki Shinohara
Naphazoline is a peripheral α2-adrenergic receptor agonist commonly used as a topical decongestant. In Japan, over-the-counter antiseptics often contain naphazoline to effect local hemostasis. We present the first case involving the development of hypercoagulopathy, with kidney and liver dysfunction, following a naphazoline overdose. A 22-year-old Japanese woman with a history of depression ingested 160 mL of a commercially available antiseptic containing 0.1% naphazoline. Three days later, she was brought to the emergency department because of general fatigue, nausea, and vomiting...
2017: Case Reports in Emergency Medicine
https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#17
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28524363/donor-transmitted-mutation-of-the-abcb11-gene-and-ensuing-intra-hepatic-cholestasis-of-pregnancy-in-a-liver-transplant-recipient
#18
Tiong Yeng Lim, Iona Coltart, Pierre Foskett, Richard Thompson, Sandra Strautnieks, Leonie Penna, Catherine Williamson, Rosa Miquel, Michael A Heneghan
In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30-year-old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10-50), GGT 25 IU/L (normal range 1-55), bilirubin 1...
May 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28502983/alkaline-phosphatase-a-novel-treatment-target-for-cardiovascular-disease-in-ckd
#19
REVIEW
Mathias Haarhaus, Vincent Brandenburg, Kamyar Kalantar-Zadeh, Peter Stenvinkel, Per Magnusson
Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney...
July 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#20
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
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