Elevation of autoantibodies to cerebral proteins in hepatic encephalopathy: Another pathogenic factor?

2021 ◽  
Author(s):  
Elina Manzhalii ◽  
Tetyana M Falalyeyeva ◽  
Valentyna O. Moyseyenko ◽  
Ralf Weiskirchen ◽  
Wolfgang Stremmel
Keyword(s):  
Hepatic Encephalopathy ◽  
Brain Dysfunction ◽  
Cell Swelling ◽  
Pathogenic Factor ◽  
Contributing Factors ◽  
Serum Autoantibody ◽  
Ammonia Accumulation ◽  
Immune Mediated ◽  
Experimental Rat Model ◽  
New Perspective

Background: The pathophysiology of hepatic encephalopathy is incompletely understood. It remains illusive how the contributing factors of neuronal ammonia accumulation, cell swelling and inflammation interact. Objective: Correlation of neuronal autoantibody levels to the degree of hepatic encephalopathy as first indication of immune mediated pathogenesis. Methods: We investigated serum autoantibody levels of representative brain proteins in patients with hepatic encephalopathy as well as in an experimental rat model with cirrhosis and hepatic encephalopathy after carbon tetrachloride exposure. They were examined in relation to presence of hepatic encephalopathy and the degree of neurological impaiment evaluated by quantitative scores. Results: In hepatic encephalopathy an increase of all of the examined antibodies was observed in serum. The grade of antibody elevation correlated to the degree of encephalopathy registered by quantitative evaluation of brain dysfunction. Conclusion: The degree of hepatic encephalopathy parallels neuronal autoantibody elevation. In case a causal relationship could finally be established, it adds to the understanding of hepatic encephalopathy and may open a new perspective for treatment of this handicaping condition by immunosuppressive strategies.

scholarly journals Lights and Shadows in Hepatic Encephalopathy Diagnosis

2021 ◽  
Vol 10 (2) ◽  
pp. 341
Author(s):  
Piero Amodio ◽  
Sara Montagnese
Keyword(s):  
Risk Factors ◽  
Differential Diagnosis ◽  
Hepatic Encephalopathy ◽  
Brain Dysfunction ◽  
Exact Nature ◽  
Multidimensional Approach ◽  
Liver Insufficiency ◽  
Historical Origins

Hepatic encephalopathy (HE) is a form of brain dysfunction that is caused by liver insufficiency and/or portal-systemic shunting. The exact nature of HE is debated; as such, conflicting uses of the term “HE” may cause inconsistencies in its detection and management. This review highlights the meaning of the term “HE” on the basis of its historical origins and current consensus. It also provides criteria for the diagnosis of the condition based on its phenotypes and risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical reporting of HE episodes is discussed.

scholarly journals Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis

2021 ◽  
Vol 8 (1) ◽  
pp. e000648
Author(s):  
Gilles Jadd Hoilat ◽  
Mohamad Fekredeen Ayas ◽  
Judie Noemie Hoilat ◽  
Ahmed Abu-Zaid ◽  
Ceren Durer ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Hepatic Encephalopathy ◽  
Web Of Science ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Brain Dysfunction ◽  
Cochrane Library ◽  
Continuous Data ◽  
Inverse Variance ◽  
Scoring Algorithm

BackgroundHepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators.MethodsWe screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE.ResultsFour trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=−0.68, 95% CI (−1.05 to –0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=−1.45, 95% CI (−1.72 to –1.18), p<0.001) in favour of patients treated with PEG.ConclusionPEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.

scholarly journals Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

2016 ◽  
Vol 7 ◽  
pp. 645-654 ◽  
Author(s):  
Bin Song ◽  
Yanli Zhang ◽  
Jia Liu ◽  
Xiaoli Feng ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Titanium Dioxide ◽  
Molecular Mechanisms ◽  
Titanium Dioxide Nanoparticles ◽  
Brain Dysfunction ◽  
In Vivo Studies ◽  
Cell Components ◽  
New Perspective ◽  
The Brain

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

Acetylcholinesterase activity in an experimental rat model of Type C hepatic encephalopathy

2011 ◽  
Vol 113 (3) ◽  
pp. 358-362 ◽  
Author(s):  
Marta Méndez ◽  
Magdalena Méndez-López ◽  
Laudino López ◽  
María A. Aller ◽  
Jaime Arias ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Rat Model ◽  
Acetylcholinesterase Activity ◽  
Experimental Rat Model ◽  
Type C

scholarly journals Aberrant caveolin-1–mediated Smad signaling and proliferation identified by analysis of adenine 474 deletion mutation (c.474delA) in patient fibroblasts: a new perspective on the mechanism of pulmonary hypertension

2017 ◽  
Vol 28 (9) ◽  
pp. 1177-1185 ◽  
Author(s):  
Glenn Marsboom ◽  
Zhenlong Chen ◽  
Yang Yuan ◽  
Yanmin Zhang ◽  
Chinnaswamy Tiruppathi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Critical Role ◽  
Null Mouse ◽  
Type I ◽  
Contributing Factors ◽  
Smad Signaling ◽  
Caveolin 1 ◽  
Tgfβ Receptors ◽  
C Terminus ◽  
New Perspective

A heterozygous caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to a caveolin-1 protein that contains all known functional domains but has a change in only the final 20 amino acids of the C-terminus. Here we studied how this mutation alters caveolin-1 function, using patient-derived fibroblasts. Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation form typical caveolae. Expression of mutated caveolin-1 in caveolin-1–null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum. However, coexpression of wild-type caveolin-1 with mutated caveolin-1 restored the ability to form caveolae. Importantly, fibroblasts carrying the mutation showed twofold increase in proliferation rate associated with hyperphosphorylation of Smad1/5/8. This mutation impaired the antiproliferative function of caveolin-1. Inhibition of type I TGFβ receptors ALK1/2/3/6 responsible for phosphorylation of Smad1/5/8 reduced the hyperproliferation seen in c.474delA fibroblasts. These results demonstrate the critical role of the final 20 amino acids of caveolin-1 in modulating fibroblast proliferation by dampening Smad signaling and suggest that augmented Smad signaling and fibroblast hyperproliferation are contributing factors in the pathogenesis of PAH in patients with caveolin-1 c.474delA mutation.

scholarly journals Hepatic encephalopathy: modern aspects of diagnosis and treatment

2021 ◽  
pp. 90-98
Author(s):  
S. D. Podymova ◽  
E. V. Vinnitskaya ◽  
T. Yu. Khaimenova
Keyword(s):  
Liver Transplantation ◽  
Hepatic Encephalopathy ◽  
Brain Dysfunction ◽  
Controlled Trials ◽  
Psychometric Tests ◽  
Effective Strategy ◽  
New Approach ◽  
Randomized Controlled ◽  
Detailed Assessment ◽  
Severity Of The Disease

A new approach to the diagnosis of PE has been the identification of latent and overt PE in recent years. The detailed assessment of the stages of PE presented in the paper actually reflects the severity of the disease. The diagnosis of latent PE is established based on the results of at least two psychometric tests repeated in dynamics, and the data of one computerized test. The diagnosis of apparent PE is often made by “excluding” other possible causes of brain dysfunction. It is shown that effective therapy of PE is based not only on the features of the pathogenesis, but is impossible without taking into account the various variants of the course of PE, the severity of the disease. Based on randomized controlled trials conducted in recent years, an effective strategy for the treatment of various forms of PE has been developed: episodic, recurrent. Recurrent, therapy-resistant, and obvious PE in the presence of hepatic insufficiency is an indication for liver transplantation.

Management of acute hepatic failure in the critically ill

2016 ◽  
Author(s):  
Deepak Joshi ◽  
Georg Auzinger
Keyword(s):  
Liver Transplantation ◽  
Hepatic Encephalopathy ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Hepatic Failure ◽  
Brain Dysfunction ◽  
Hepatic Necrosis ◽  
Multisystem Disorder ◽  
Grade Iii ◽  
Viable Treatment

Acute liver failure occurs in patients with acute hepatic necrosis resulting in hepatic encephalopathy, jaundice and coagulopathy. Acute liver failure is a multisystem disorder. The management is initially supportive. Intravenous N-acetylcysteine is recommended for all patients. Brain dysfunction is common. Elective intubation is recommended for all patients who develop Grade III hepatic encephalopathy. Liver transplantation is an appropriate and viable treatment for acute liver failure. Early and safe transfer to a transplant centre for transplant assessment is advised.

scholarly journals Role of Toll-Like Receptor 4 on Lupus Lung Injury and Atherosclerosis in LPS-Challenge ApoE−/−Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jing-qin Ni ◽  
Qiufang Ouyang ◽  
Ling Lin ◽  
Ziyang Huang ◽  
Huixia Lu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Interleukin 1 ◽  
Intima Media Thickness ◽  
Immunofluorescent Staining ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Serum Autoantibody ◽  
Lps Challenge ◽  
Immune Mediated

To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE−/−or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines of interferon-gamma (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1 (IL-1β) were assessed by ELISA. Hematoxylin and eosin (HE) and Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis were employed. TLR4 in macrophages was detected by double immunofluorescent staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF-κB p65), and B cell activating factor belonging to the TNF family (BAFF) were examined by immunohistochemistry. We found that serum autoantibody (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery were obviously increased after LPS challenge in both genotypes, but to a lesser extent in wild-type strains. And those alterations were alleviated by coadministration of LPS and TAK-242. Mechanistically, upregulation of TLR4, NF-κb, and BAFF was involved. We concluded that TLR4/NF-κb/BAFF in macrophages might be a possible common autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will be a therapeutic target in atherosclerosis and immune-mediated lung injury.

scholarly journals Two distinct immunopathological profiles in autopsy lungs of COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ronny Nienhold ◽  
Yari Ciani ◽  
Viktor H. Koelzer ◽  
Alexandar Tzankov ◽  
Jasmin D. Haslbauer ◽  
...  
Keyword(s):  
Immune Responses ◽  
Normal Lung ◽  
Pathogenic Factor ◽  
Blood Biomarkers ◽  
Viral Loads ◽  
Interferon Stimulated Genes ◽  
Immune Mediated ◽  
Pulmonary Damage ◽  
Reaction Patterns ◽  
Local Expression

Abstract Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

Glutamine as a pathogenic factor in hepatic encephalopathy

2001 ◽  
Vol 65 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Jan Albrecht ◽  
Monika Doli?ska
Keyword(s):  
Hepatic Encephalopathy ◽  
Pathogenic Factor
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