Recombinant human soluble thrombomodulin ameliorates acetaminophen-induced liver toxicity in mice.

Recombinant human soluble thrombomodulin ameliorates acetaminophen-induced liver toxicity in mice. Exp Ther Med. 2019 Aug;18(2):1323-1330 Authors: Kuwano A, Kohjima M, Suzuki H, Yamasaki A, Ohashi T, Imoto K, Kurokawa M, Morita Y, Kato M, Ogawa Y Abstract Recombinant human soluble thrombomodulin alpha (rhTM) has been developed as an anticoagulant with anti-inflammatory activity. Notably, acetaminophen (APAP) -induced liver disease (AILI) is caused by direct metabolite-induced hepatotoxicity as well as hepatic hyper-coagulation. To evaluate the utility of anticoagulant for the treatment of AILI, rhTM was administered in a mouse AILI model and liver damage was analyzed. AILI was induced in 8-week-old mice by intraperitoneal injection of APAP. rhTM (20 mg/kg) or placebo was injected at the same time as APAP administration. Serum alanine aminotransferase, fibrin degradation products and high-mobility group box 1 levels were significantly decreased in the rhTM-treated group compared with the control group. Furthermore, rhTM reduced the necrotic area and fibrin deposition in liver sections. rhTM suppressed the mRNA expression of heme oxygenase-1, plasminogen activator inhibitor type-1, tissue factors, and inflammatory cytokines compared with the control group. rhTM did not change the hepatic GSH content at 2 h after APAP injection, but restored them at 4 h after the insult. rhTM ameliorated liver damage in mice with AILI, probably via the improvement in liver p...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research

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CONCLUSIONS: Most cirrhotic children in this cohort study had evidence of IPVD by positive SBT. However, none of these met the criteria for diagnosis of HPS. This evidence of IPVD subsided after LT. PMID: 31320167 [PubMed]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
cute;thé Z Abstract In the last decades, the results of liver transplantation have shown significant improvement. More patients are eligible for liver transplantation, while the indications are changing. The worldwide shortage of donor organs urges the profession for the development of new strategies. With rational extension of donor criteria, more precise organ allocation, personalized donation, living related donation, machine perfusion, and donation after cardiac death, liver transplantation is becoming available for more and more patients suffering from end stage liver disease. Hereby we summarize the n...
Source: Orvosi Hetilap - Category: General Medicine Authors: Tags: Orv Hetil Source Type: research
AbstractBackgroundLiver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) is influenced by liver fibrosis and hepatic perfusion pressure. VCTE-based controlled attenuation parameter (CAP) is a noninvasive marker for hepatic steatosis (HS).AimsTo investigate the diagnostic performance of CAP in patients with advanced chronic liver disease (ACLD)/portal hypertension (PHT: hepatic venous pressure gradient (HVPG)  ≥ 6 mmHg).MethodsEighty-eight patients with LS  ≥ 10 kPa and/or HVPG ≥ 6 mmHg who underwent simultaneous liver biopsy, CAP...
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
Non-alcoholic fatty liver disease (NAFLD) is associated with high cardiovascular morbidity and mortality which usually is considered to be related to cardiac involvement, while scarce attention is addressed to brain damage. Viceversa NAFLD is associated with asymptomatic brain lesions, alterations in cerebral perfusion and activity, cognitive impairment and brain aging and with increased risk and severity of both ischemic and haemorrhagic stroke. Besides known metabolic risk factors, NAFLD is characterized by a pro inflammatory state, which contributes to atherosclerosis and microglia activation, endothelial dysfunction, p...
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Liver, Pancreas and Biliary Tract Source Type: research
1437Objectives: Phase analysis parameters on gated SPECT myocardial perfusion imaging (MPI) have been proven reliable in assessment of left ventricular mechanical dyssynchrony (LVMD). Patients with end-stage liver disease (ESLD) are known to develop cardiovascular complications, especially in the form of cirrhotic cardiomyopathy. This entity, while mostly occult can lead to major adverse cardiac events (MACEs), thus increasing morbidity and mortality in ESLD patients posted for liver transplantation (LT). As part of the pre-transplant workup, the patients are routinely subjected to echocardiography and stress SPECT MPI for...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Cardiovascular Clinical Science Posters Source Type: research
162Objectives: Stress myocardial blood flow (sMBF) and coronary flow reserve (CFR) by cardiac positron emission tomography (cPET) have been shown to provide prognostic information supplemental to relative perfusion images. However, myocardial blood flow (MBF) has not been characterized in patients with end stage liver disease (ESLD). Characterization of MBF may provide additional physiologic information to further assist with management and risk stratification for patients undergoing liver transplantation. Methods: A total of 126 patients with ESLD undergoing liver transplant evaluation that underwent rubidium-82 cPET with...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Cardiovascular Clinical Science: Advances in Clinical Utility of Myocardial Blood Flow Quantification Source Type: research
ConclusionFor the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2 and T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms.Key Points• DAAs have revolutionised the treatment of hepatitis C and achieve sustained virological response in over 95% of pa...
Source: European Radiology - Category: Radiology Source Type: research
Conclusion Massive SI and immune cell paralysis associated with ACLF represent the extreme severity of CAID in response to an infectious or sterile challenge. The severe immune disturbance plays a pivotal role in the pathogenesis of the distinctive features of ACLF: organ failure and bacterial infection susceptibility. Excessive SI in ACLF results from the massive activation and dysfunction of an innate immune system challenged by increased PAMPs and DAMPs. SI leads to cell and tissue immunopathology contributing to hepatic and extrahepatic organ failure. Concomitantly, the course of ACLF is associated with a disproportio...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, TSF improved lipid accumulation and hepatic steatosis by inducing the AMPK/SIRT1 pathway-mediated autophagy. Introduction Nonalcoholic fatty liver disease (NAFLD) has become a worldwide health concern due to the increased incidence of obesity and diabetes. In addition, NAFLD is closely associated with the risk factors of coronary heart disease, such as metabolic syndrome, diabetes mellitus, and dyslipidemia, which are considered to be the leading causes of death (Wiest et al., 2017). Although our understanding of the pathogenesis of NAFLD has significantly improved, there is still no effective medica...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
This study was conducted strictly according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) (Moher et al., 2009). A systematic literature search was performed in Pubmed, Embase, and ISI Web of Science using the medical terminologies described in Table S1, with the language restriction limited to English (updated until 20 January 2019). Details of the search strategy in each database are presented in Table S1. Inclusion Criteria Given the study purpose, we attempted to conduct a broad search that included literature involving continuous risks of all post-operational outcome...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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