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Hepatic microcirculation

Kamil Kus, Edyta Kus, Agnieszka Zakrzewska, Wojciech Jawien, Barbara Sitek, Maria Walczak, Stefan Chlopicki
PURPOSE: To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. METHODS: C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes...
February 2, 2017: Pharmacological Reports: PR
Tzu-Hao Li, Chih-Wei Liu, Pei-Chang Lee, Chia-Chang Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Ying-Ying Yang, Shie-Liang Hsieh, Han-Chieh Lin, Chang-Youh Tsai
BACKGROUND: 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...
March 16, 2017: Journal of the Chinese Medical Association: JCMA
Nicole L Mendell, Donald H Bouyer, David H Walker
BACKGROUND: Scrub typhus, a febrile illness of substantial incidence and mortality, is caused by infection with the obligately intracellular bacterium Orientia tsutsugamushi. It is estimated that there are more than one million cases annually transmitted by the parasitic larval stage of trombiculid mites in the Asia-Pacific region. The antigenic and genetic diversity of the multiple strains of O. tsutsugamushi hinders the advancement of laboratory diagnosis, development of long-lasting vaccine-induced protection, and interpretation of clinical infection...
March 2017: PLoS Neglected Tropical Diseases
Anabel Fernández-Iglesias, Jordi Gracia-Sancho
Liver microcirculation plays an essential role in the progression and aggravation of chronic liver disease. Hepatic sinusoid environment, mainly composed by hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, intimately cooperate to maintain global liver function and specific phenotype of each cell type. However, continuous liver injury significantly deregulates liver cells protective phenotype, leading to parenchymal and non-parenchymal dysfunction. Recent data have enlightened the molecular processes that mediate hepatic microcirculatory injury, and consequently, opened the possibility to develop new therapeutic strategies to ameliorate liver circulation and viability...
2017: Frontiers in Medicine
Roland C Schelker, Ana P Barreiros, Christina Hart, Wolfgang Herr, Ernst-Michael Jung
AIM: To evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia (HHT) patients by ultrasound (US) considering quantitative analytic methods. METHODS: The imaging features on US and contrast-enhanced ultrasound (CEUS) in 18 patients diagnosed with HHT were retrospectively analyzed. Regarding CEUS, real-time contrast harmonic imaging and sulfur hexafluoride-filled microbubbles were used. RESULTS: HVaMs were identified in all 18 patients...
January 21, 2017: World Journal of Gastroenterology: WJG
Marina Vilaseca, Héctor García-Calderó, Erica Lafoz, Oihane García-Irigoyen, Matías Avila, Joan Carles Reverter, Jaume Bosch, Virginia Hernández-Gea, Jordi Gracia-Sancho, Joan Carles García-Pagán
BACKGROUND & AIMS: In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension development. Hepatic Stellate Cells (HSC) play a major role increasing IHVR as when activated are contractile and promote fibrogenesis. Protease activated receptors (PARs) can activate HSC, through thrombin and factor Xa which are known PARs agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant rivaroxaban, a direct anti-factor Xa, on HSC phenotype, liver fibrosis, liver microthrombosis and portal hypertension in cirrhotic rats...
January 31, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Carlo Pulitano, David Joseph, Charbel Sandroussi, Deborah Verran, Phong Ho, Ashe Debiasio, Adriano Luongo, Geoffrey W McCaughan, Nicholas A Shackel, Michael Crawford
Despite the growing data supporting the role of microcirculation in regulating liver function, little of this knowledge has been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in vivo using sidestream dark field (SDF) imaging and correlate these findings with hepatic blood flow, hemodynamic parameters, and soluble mediators. Postreperfusion hepatic microcirculation was assessed using SDF imaging. Hepatic microcirculation measurements included functional sinusoidal density (cm/cm(2) ), sinusoidal diameter (μm), red blood cell velocity (μm/second), volumetric blood flow (pl/second), and flow heterogeneity (FH) index...
April 2017: Liver Transplantation
Chong Hui Li, Xin Lan Ge, Ke Pan, Peng Fei Wang, Yi Nan Su, Ai Qun Zhang
OBJECTIVE: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. This study was designed to monitor and characterize the hepatic microcirculatory perfusion following different volumes of hepatectomy in rats by using laser speckle contrast image (LSCI) and Oxygen to See (O2C), a spectrometric device. METHODS: The microcirculatory liver blood flow of the rats that underwent 68%, 85% and 90% hepatectomy (68PH, 85PH and 90PH) was monitored with LSCI and O2C before and following the hepatectomy...
November 25, 2016: Microvascular Research
Emil Iskandarov, Pramod Kadaba Srinivasan, Wang Xin, Christian Bleilevens, Mamdouh Afify, Astrit Hamza, Lai Wei, Koichiro Hata, Boyukkishi Agayev, Rene Tolba
OBJECTIVES: To investigate the role of CGS21680, a selective adenosine A2A receptor agonist, on a bile-duct-ligated cirrhotic liver resection model in rats. METHODS: Male Wistar rats were allotted into 3 groups (n = 7 per time-point): the control group, the bile duct ligation + CGS21680 group (BDL + CGS), and the bile duct ligation group (BDL). Biliary cirrhosis had been previously induced by ligature of the common bile duct in the BDL + CGS and BDL groups. After 2 weeks, the animals underwent partial hepatectomy (50%)...
August 2016: Hepatitis Monthly
Marcos L Miranda, Michelle M Balarini, Daniela S Balthazar, Lorena S Paes, Maria-Carolina S Santos, Eliete Bouskela
BACKGROUND: Experimental data suggest that ivabradine, an inhibitor of the pacemaker current in sinoatrial node, exerts beneficial effects on endothelial cell function, but it is unclear if this drug could prevent microcirculatory dysfunction in septic subjects, improving tissue perfusion and reducing organ failure. Therefore, this study was designed to characterize the microcirculatory effects of ivabradine on a murine model of abdominal sepsis using intravital videomicroscopy. METHODS: Twenty-eight golden Syrian hamsters were allocated in four groups: sham-operated animals, nontreated septic animals, septic animals treated with saline, and septic animals treated with ivabradine (2...
January 2017: Anesthesiology
Niteen Tapuria, Sameer Junnarkar, Mahmoud Abu-Amara, Barry Fuller, Alexander M Seifalian, Brian R Davidson
AIM: To investigate the hepatic microcirculatory changes due to Haemoxygenase (HO), effect of HO inhibition on remote ischemic preconditioning (RIPC) and modulation of CINC. METHODS: Eight groups of animals were studied - Sham, ischemia reperfusion injury (IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion, RIPC (remote ischemic preconditioning) + IRI group, remote ischemic preconditioning in sham (RIPC + Sham), PDTC + IR (Pyridodithiocarbamate, HO donor), ZnPP + RIPC + IRI (Zinc protoporphyrin prior to preconditioning), IR-24 (45 min of ischemia followed by 24 h of reperfusion), RIPC + IR-24 (preconditioning prior to IR)...
September 7, 2016: World Journal of Gastroenterology: WJG
Muhamad Marlini, Ayako Mabuchi, Beth L Mallard, Ngatiman Hairulhisyam, Sachiko Akashi-Takamura, Jacquie L Harper, Antony M Wheatley
What is the central question of this study? The liver regenerative process is complex and involves a sequence of signalling events, but the possible involvement of structural and haemodynamic changes in vivo during this process has never been explored. What is the main finding and its importance? Normal sinusoidal blood flow and velocity are crucial for a normal regenerative response, and delays in these haemodynamic events resulted in impaired liver regeneration in lipopolysaccharide-insensitive, C3H/HeJ mice...
December 1, 2016: Experimental Physiology
A Daliry, R Rangel Silvares, E N G da Silva Pereira, E E Ilaquita Flores, V Estato, P A Reis, I José da Silva, M P Machado, H C de Castro F Neto, E Tibiriça
OBJECTIVE: As several studies have shown a link between T1D and liver disease we explored the hepatic alterations due to diabetes and the modulation of this complication by the metformin adjunct therapy. DESIGN AND METHOD: Fifty five Wistar rats were divided in three groups: control (CTL, n = 20), high-fat diet/streptozotocin induced diabetic (DM, n = 20) and diabetic treated with metformin plus insulin (DM + Met + Ins, n = 15). The biochemical parameters (%HbA1c, cholesterol, fructosamine, triglycerides, total proteins, bilirubin, urea, uric acid, and ALT, AST, ALP, GGT, and amylase activities) were analyzed by spectrophotometry...
September 2016: Journal of Hypertension
Stefano Fiorucci, Eleonora Distrutti
Cirrhosis is a end-stage disease of the liver in which fibrogenesis, angiogenesis and distortion of intrahepatic microcirculation lead to increased intrahepatic resistance to portal blood flow, a condition known as portal hypertension. Portal hypertension is maintained by a variety of molecular mechanisms including sinusoidal endothelial cells (LSECs) hyporeactivity, activation of hepatic stellate cells (HSCs), reduction in hepatic endothelial nitric oxide synthase (eNOS) activity along with increased eNOS-derived NO generation in the splanchnic and systemic circulations...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Dong Zhang, Xiao-Jing Song, Shun-Yue Li, Shu-You Wang, Bing-Jun Chen, Xiao-Dong Bai, Li-Mei Tang
Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect...
2016: Scientific Reports
Jiehua Qiu, Weimin Zhou, Wei Zhou, Xinhua Tang, Qingwen Yuan, Xianhua Zhu, Yujin Yang, Jixin Xiong
BACKGROUND: The purpose of our study is to analyze the methods of treating infected femoral artery pseudoaneurysms (IFAPs), and also to identify the most appropriate method, especially for patients with a long history of drug abuse. METHODS: A retrospective chart review of 88 consecutive IFAPs secondary to drug abuse between 2003 and 2014 was performed. Outpatient clinic charts were reviewed, as well as inpatient and anesthesia records. All patients had undergone a computer tomography angiography or contrast computer tomography to confirm their diagnosis...
October 2016: Annals of Vascular Surgery
Raquel Rangel Silvares, Evelyn Nunes Goulart da Silva Pereira, Edgar Eduardo Ilaquita Flores, Vanessa Estato, Patrícia Alves Reis, Igor José da Silva, Marcelo Pelajo Machado, Hugo Caire de Castro Faria Neto, Eduardo Tibiriça, Anissa Daliry
In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM + Ins) or metformin plus insulin (DM + Met + Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression...
June 2016: International Journal of Experimental Pathology
Edwin C Y Chow, Jason Z Ya Wang, Holly P Quach, Hui Tang, David C Evans, Albert P Li, Jose Silva, K Sandy Pang
Chimeric mouse liver models are useful in vivo tools for human drug metabolism studies; however, liver integrity and the microcirculation remain largely uninvestigated. Hence, we conducted liver perfusion studies to examine these attributes in FRGN [Fah(-/-), Rag2(-/-), and Il2rg(-/-), NOD strain] livers (control) and chimeric livers repopulated with mouse (mFRGN) or human (hFRGN) hepatocytes. In single-pass perfusion studies (2.5 ml/min), outflow dilution profiles of noneliminated reference indicators ((51)Cr-RBC, (125)I-albumin, (14)C-sucrose, and (3)H-water) revealed preservation of flow-limited distribution and reduced water and albumin spaces in hFRGN livers compared with FRGN livers, a view supported microscopically by tightly packed sinusoids...
September 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Dmitry Victorovich Garbuzenko, Nikolay Olegovich Arefyev, Dmitry Vladimirovich Belov
PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: "Liver cirrhosis", "Endothelial dysfunction", "Sinusoidal remodeling", "Intrahepatic angiogenesis" and "Pathogenesis of portal hypertension". Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis...
June 8, 2016: World Journal of Hepatology
Shengyan Xi, Lifeng Yue, Mengmeng Shi, Ying Peng, Yangxinzi Xu, Xinrong Wang, Qian Li, Zhijun Kang, Hanjing Li, Yanhui Wang
Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
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