Shock
Department of Anaesthesiology and Critical Care Therapy, Friedrich-Schiller-University, Jena, Germany.
Published: October 2009
Liver dysfunction affects a variety of metabolic pathways in the critically ill, but mechanisms remain poorly understood. We prospectively assessed markers of hepatic injury and function in sepsis and I/R injury in vivo and molecular mechanisms in human liver tissue ex vivo. Markers of hepatocellular injury, synthesis, and excretion, including plasma disappearance rate of indocyanine green (ICG), were measured in 48 patients with severe sepsis. Incidence of liver dysfunction was 42% as assessed by hyperbilirubinemia but 74% by impaired dye excretion. Conventional markers for liver injury failed to predict outcome, whereas dye excretion of less than 8% per minute predicted death with high sensitivity and specificity. Potential mechanisms were assessed via (a) gene expression analysis of transporter proteins for bilirubin and ICG in cultured human liver tissue, and (b) monitoring uptake and excretion of the dye after I/R injury in 12 patients receiving a biliary T-tube during liver transplantation. Ex vivo gene expression of transporters was differentially affected for bilirubin and ICG with upregulation of basolateral and downregulation of canalicular ICG transporters. Consistently, patients with unfavorable course after liver transplantation displayed almost complete cessation of biliary dye excretion, whereas uptake into the hepatocyte was reduced by only 40%. In conclusion, standard liver tests lack the required sensitivity to assess hepatic injury and function in the critically ill. Dye excretion better reflects excretory and/or microvascular dysfunction but still underestimates impaired canalicular transport. The observed differential susceptibility of the polar surfaces of human hepatocytes has potential implications for monitoring liver function and drug-induced liver injury.
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http://dx.doi.org/10.1097/SHK.0b013e31819d8204 | DOI Listing |
Int J Mol Sci
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Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Despite significant advancements in bioimaging technology, only a limited number of fluorophores are currently approved for clinical applications. Indocyanine green (ICG) is the first FDA-approved near-infrared (NIR) fluorophore and has significantly advanced clinical interventions over the past three decades. However, its single-channel imaging at 800 nm emission is often insufficient for capturing comprehensive diagnostic information during surgery.
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Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Private Bag X20, Hatfield, Pretoria 0028, South Africa.
The progressive development of resistance in to almost all available antibiotics has made it crucial to develop novel approaches to tackling multi-drug resistance (MDR). One of the primary causes of antibiotic resistance is the over-expression of the MtrCDE efflux pump protein, making this protein a vital target for fighting against antimicrobial resistance (AMR) in . This study was aimed at evaluating the potential MtrCDE efflux pump inhibitors (EPIs) and their stability in treating gonorrhoea infection.
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Department of Gastroenterological Surgery, Miyagi Cancer Center, Natori, Japan.
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Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China.
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Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:
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