scholarly journals Important Role of P-Selectin for Leukocyte Recruitment, Hepatocellular Injury, and Apoptosis in Endotoxemic Mice

2004 ◽  
Vol 11 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Daniel Klintman ◽  
Xiang Li ◽  
Henrik Thorlacius
Keyword(s):  
Liver Injury ◽  
Liver Enzymes ◽  
Leukocyte Recruitment ◽  
Leukocyte Rolling ◽  
Hepatocellular Injury ◽  
Principal Role ◽  
Step Procedure ◽  
Pathophysiological Role ◽  
The Individual

ABSTRACT Leukocyte recruitment in the liver includes a two-step procedure in which selectin-dependent leukocyte rolling is a prerequisite for subsequent CD18-dependent leukocyte firm adhesion in postsinusoidal venules. However, the roles of the individual selectins in leukocyte rolling and adhesion, hepatocellular injury, and apoptosis remain elusive. Therefore, we examined the pathophysiological role of P-, E-, and L-selectin in male C57BL/6 mice challenged with lipopolysaccharide (LPS) and d-galactosamine (Gal) by use of intravital microscopy of the liver microcirculation. In control animals, administration of LPS-Gal provoked reproducible hepatic damage, including marked increases of leukocyte recruitment, liver enzymes, and hepatocyte apoptosis and reduced sinusoidal perfusion. Interestingly, pretreatment with an anti-P-selectin antibody (RB40.34) markedly reduced leukocyte rolling and firm adhesion by 65 and 71%, respectively. Moreover, interference with P-selectin function significantly improved sinusoidal perfusion and reduced the increase in liver enzymes by 49 to 84% in endotoxemic mice. Moreover, the activity of caspase-3 and the number of apoptotic hepatocytes were significantly reduced by 55 and 54%, respectively, in RB40.34-treated animals. In contrast, administration of an anti-E-selectin antibody (10E9.6) and an anti-L-selectin antibody (Mel-14) did not protect against endotoxin-induced leukocyte responses or hepatic injury. In conclusion, our novel findings document a principal role of P-selectin in mediating leukocyte rolling, a precondition to the subsequent firm adhesion of leukocytes in liver injury. Furthermore, our novel data demonstrate that inhibition of P-selectin function reduces hepatocellular injury and apoptosis, suggesting a causal relationship between leukocyte recruitment on one hand and hepatocellular injury and apoptosis on the other hand. Based on these findings, it is suggested that P-selectin may be an important therapeutic target in endotoxin-induced liver injury.

scholarly journals Role of Liver Enzymes in Patients with Blunt Abdominal Trauma to Diagnose Liver Injury

2020 ◽  
Author(s):  
Anup Shrestha ◽  
Harish Chandra Neupane ◽  
Kishor Kumar Tamrakar ◽  
Abhishek Bhattarai ◽  
Gaurav Katwal
Keyword(s):  
Liver Injury ◽  
Confidence Interval ◽  
Ct Scan ◽  
Abdominal Trauma ◽  
Blunt Abdominal Trauma ◽  
Predictive Value ◽  
Liver Enzymes ◽  
Tertiary Center ◽  
Significant Difference

Abstract Background:The liver is the second most injured organ following blunt abdominal trauma (BAT) after spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it is not readily available in the hospital. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury.Method:The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) study from February 2019 to May 2020. During that period 96 patients with BAT presented to the emergency department(ED) of CMCTH.Results:Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (<0.001) between patients with liver injury and no liver injury. The area under the ROC curve of AST was 0.89(95% Confidence Interval 0.86-0.98) and of ALT was 0.92(95% Confidence Interval 0.83-0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7 %, a specificity of 90 %, a positive predictive value of 86.8 %, and a negative predictive value of 77.6 %. The corresponding values for ALT ≥ 80 U/l were 77.8 %, 94.1%, 92.1% and 82.8 %, respectively.ConclusionIn conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l respectively. The elevated level of AST and ALT might assist the surgeons to timely refer the suspected patients with the liver to a tertiary center and it might help the surgeons to go for conservative management for minor liver injuries in BAT preventing the exposure hazards of the CT scan.

Hydralazine-induced liver injury: a review and discussion

2021 ◽  
Vol 14 (8) ◽  
pp. e243278 ◽  
Author(s):  
Meeta Bhardwaj ◽  
Nakul Jay Bhardwaj ◽  
Kendra Cueto ◽  
T Colin Killeen
Keyword(s):  
Side Effects ◽  
Liver Injury ◽  
Antihypertensive Agent ◽  
Adverse Reactions ◽  
Liver Enzymes ◽  
Injury Pattern ◽  
Hypertension Management ◽  
Close Monitoring ◽  
Hepatocellular Injury ◽  
Specific Symptoms

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine’s hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient’s liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.

scholarly journals Enoxaparin-Induced Liver Injury

2020 ◽  
Vol 14 (2) ◽  
pp. 315-319 ◽  
Author(s):  
Shehriyar Mehershahi ◽  
Nikhitha Mantri ◽  
Aneesh Kumar ◽  
Shaikh Danial ◽  
Patel Harish
Keyword(s):  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Liver Injury ◽  
Low Molecular Weight Heparin ◽  
Liver Enzymes ◽  
Low Molecular Weight ◽  
Dramatic Improvement ◽  
Hepatocellular Injury

Enoxaparin, a form of low-molecular-weight heparin, can cause a rare, underreported, and often reversible form of hepatocellular injury. This report describes a case of enoxaparin-induced hepatotoxicity in a 61-year-old male diagnosed with pulmonary embolism. Elevations of liver enzymes were noted within 1 week of starting the drug, followed by a dramatic improvement upon its discontinuation, with subsequent normalization in the following days.

Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP

2012 ◽  
Vol 303 (4) ◽  
pp. G498-G506 ◽  
Author(s):  
Jörn M. Schattenberg ◽  
Michael Nagel ◽  
Yong Ook Kim ◽  
Tobias Kohl ◽  
Marcus A. Wörns ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Hepatocellular Injury ◽  
Inhibitory Protein ◽  
Hepatocellular Apoptosis ◽  
Specific Deletion

Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts promotes hepatic fibrosis and the progression to cirrhosis with deleterious effects on liver physiology. The role of apoptosis signaling pathways in the development of fibrosis remains undefined. The aim of the current study was to determine the involvement of the caspase-8 homologue cellular FLICE-inhibitory protein (cFLIP) during the initiation and progression of fibrosis. Liver injury and fibrosis from carbon tetrachloride (CCl4) and thioacetamide (TAA) were examined in mice exhibiting a hepatocyte-specific deletion of cFLIP ( flip −/−). Acute liver injury from CCl4 and TAA were enhanced in flip −/− mice. This was accompanied by increased activation of caspase-3 and -9, pronounced phosphorylation of JNK, and decreased phosphorylation of Erk. Deletion of the cJun NH2-terminal kinase 2 (JNK2) in flip −/− mice protected from injury. Hepatic fibrosis was increased at baseline in 12-wk-old flip −/− mice, and progression of fibrosis from TAA was accelerated compared with the wild type. In conclusion, deletion of cFLIP in hepatocytes leads to increased fibrosis and accelerated fibrosis progression. This is accompanied by increased injury involving the activation of caspases and JNK2. Thus predisposition to liver injury involving increased hepatocellular apoptosis is a critical mediator of accelerated fibrogenesis, and prevention of liver injury will be a most important measure for patients with chronic liver disease.

scholarly journals L-Selectin Shedding Regulates Leukocyte Recruitment

2001 ◽  
Vol 193 (7) ◽  
pp. 863-872 ◽  
Author(s):  
Ali Hafezi-Moghadam ◽  
Kennard L. Thomas ◽  
Alyson J. Prorock ◽  
Yuqing Huo ◽  
Klaus Ley
Keyword(s):  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Leukocyte Rolling ◽  
Lymphocyte Function ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dependent Mechanism

The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor α–induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1–dependent mechanism. We examined the quality of leukocyte rolling and L-selectin–mediated signaling. Blockade of L-selectin shedding significantly reduced the “jerkiness” of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1–conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice.

Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1

2001 ◽  
Vol 280 (2) ◽  
pp. H634-H641 ◽  
Author(s):  
S. Bradley Forlow ◽  
Klaus Ley
Keyword(s):  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Intercellular Adhesion Molecule ◽  
Striking Similarity ◽  
Leukocyte Rolling ◽  
Intercellular Adhesion Molecule 1 ◽  
Cell Recruitment ◽  
Adhesion Efficiency

To study selectin-independent leukocyte recruitment and the role of intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking all three selectins and ICAM-1 (E/P/L/I−/−) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they showed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte firm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycollate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitment was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on α4-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and α4-integrins). A striking similarity of leukocyte adhesion efficiency in E/P/L−/− and E/P/I−/− mice suggests a pathway in which leukocyte rolling through L-selectin requires ICAM-1 for adhesion and recruitment. Comparison of our data with mice lacking individual or other combinations of adhesion molecules reveal that elimination of more adhesion molecules further reduces leukocyte recruitment but the effect is less than additive.

scholarly journals Role of Liver Enzymes in Patients with Blunt Abdominal Trauma to Diagnose Liver Injury

2020 ◽  
Author(s):  
Anup Shrestha ◽  
Harish Chandra Neupane ◽  
Kishor Kumar Tamrakar ◽  
Abhishek Bhattarai ◽  
Gaurav Katwal
Keyword(s):  
Liver Injury ◽  
Confidence Interval ◽  
Abdominal Trauma ◽  
Blunt Abdominal Trauma ◽  
Predictive Value ◽  
Liver Enzymes ◽  
Categorical Variables ◽  
Tertiary Center ◽  
Significant Difference

Abstract Background:The liver is the second most injured organ following blunt abdominal trauma (BAT) after spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it is not readily available in the hospital. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury.Method:The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) study from February 2019 to May 2020. It was a prospective observational study. All the patients with BAT were received by on duty surgical residents in the Emergency Department. Based on the imaging and operative finding patients with liver injury and without liver injury were noted with the associated injury. For comparisons of clinical and grading characteristics between the two groups (liver injury and no liver injury). The Chi-squared test was used for categorical variables as appropriate, and Mann-Whitney U test used for quantitative variables (AST and ALT). The comparisons between more than two groups (grade of injury) were performed using Kruskal-Wallis test. The Receiver operating characteristic (ROC) was used to calculate the optimal cut-off value of AST and ALT.Results:Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (<0.001) between patients with liver injury and no liver injury. The area under the ROC curve of AST was 0.89(95% Confidence Interval 0.86-0.98) and of ALT was 0.92(95% Confidence Interval 0.83-0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7 %, a specificity of 90 %, a positive predictive value of 86.8 %, and a negative predictive value of 77.6 %. The corresponding values for ALT ≥ 80 U/l were 77.8 %, 94.1%, 92.1% and 82.8 %, respectively.ConclusionIn conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l respectively. The elevated level of AST and ALT might assist the emergency physicians and surgeons to timely refer the suspected patients with the liver to a tertiary center.

scholarly journals CCl4 INDUCED LIVER INJURY;

2018 ◽  
Vol 24 (05) ◽  
pp. 739-744
Author(s):  
Sana Naz ◽  
Faisal Irshad ◽  
Hina Mawani
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Enzymes ◽  
Isotonic Saline ◽  
Saline Group ◽  
Hepatocellular Injury ◽  
Albino Rat ◽  
Medical College ◽  
Group 2 ◽  
Animal House

Objectives: Evaluate the mitigating effect of aqueous extract of Ginkgobiloba (GkbE) on liver enzymes and histology in carbon tetrachloride (CCl4) induced liverinjury in albino rat. Study design: Experimental study. Setting and Duration: Animal house,Bhitai Dental and Medical College Mirpurkhas and Agriculture University Tando Jam fromAnimal house from May 2015 - August 2016. Subjects and Methods: Sixty rats were equallydivided into 3 groups Group 1- Controls (0.9% isotonic saline), Group 2- (CCl4 CCl4 1.0mg/kg intraperitoneal) and Group 3- (CCl4+ GkbE). Blood samples were collected at end ofexperiment from tail veins. Liver was obtained after rat sacrifice by cervical dislocation. Tissuewas fixed in formaldehyde and embedded in paraffin. Microscopy of 3μ tissue sections wasperformed after H & E staining. Statistix 10.0 (USA) software was used for data analysisat 95% confidence interval. Results: Four weeks GkbE administration in CCl4 rat showedsignificant amelioration of liver enzymes and improved liver histology (p=0.0001). In GkbEtreated rats, the histological changes of degeneration, fatty change, inflammatory cellinfiltration, sinusoid congestion and necrosis was minimal (p=0.0001). GkbE was provedof mitigating the hepatocellular injury inflicted by carbon tetrachloride. Conclusion: GkbEmitigates the carbon tetrachloride induced liver injury in rat model. GkbE may be used in drugand chemical induced liver injury.

scholarly journals “Bottomsets” of the lava−fed delta of James Ross Island Volcanic Group, Ulu Peninsula, James Ross Island, Antarctica

2015 ◽  
Vol 36 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Slavomír Nehyba ◽  
Daniel Nývlt
Keyword(s):  
Debris Flows ◽  
Turbidity Currents ◽  
Local Conditions ◽  
Principal Role ◽  
Depositional System ◽  
James Ross Island ◽  
Sedimentary Succession ◽  
The Individual ◽  
Distant Relation

Abstract Sedimentological study of the three geographically separated outcrops of bottom− sets of a single lava−fed delta (Pliocene) in the James Ross Island (Antarctica) allows recognition of six lithofacies.Deposits of traction currents, deposits of volcaniclastic debris flows and products of such flows transformations (both low− and high−density turbidity currents) and glacigenic deposits (subaqueous debris flows and traction/turbidity currents) were all recognised. Existence of submarine proglacial environment formed prior to formation of volcani− clastic deposits partly covering the subaqueous slopes of volcano is supposed. The principal role of mass flow processes was recognised and explained by relative steep slopes of the lava−fed delta. The distribution of lithofacies significantly differs in the individual outcrops. These variations in sedimentary succession and also in thickness of volcaniclastic deposits of “bottomsets” of the single lava fed delta suggest principal role of local conditions and paleogeography for development and preservation of this part of delta depositional system. Moreover proximal and distal setting can be followed and direct vs. more distant relation to over−riding lava−fed delta supposed. The sedimentary succession terminated by foresets of hyaloclastite breccia.

scholarly journals Role of Liver Enzymes in Patients with Blunt Abdominal Trauma to Diagnose Liver Injury

2020 ◽  
Author(s):  
Anup Shrestha ◽  
Harish Chandra Neupane ◽  
Kishor Kumar Tamrakar ◽  
Abhishek Bhattarai ◽  
Gaurav Katwal
Keyword(s):  
Liver Injury ◽  
Blood Transfusion ◽  
Confidence Interval ◽  
Abdominal Trauma ◽  
Blunt Abdominal Trauma ◽  
Predictive Value ◽  
Liver Enzymes ◽  
Tertiary Center ◽  
Significant Difference

Abstract Background: The liver is the second most injured organ following blunt abdominal trauma (BAT) after spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it is not readily available in every hospital. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury. Method: The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) from February 2019 to May 2020. During that period 96 patients with BAT presented to the emergency department(ED) of CMCTH. Results: Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (<0.001) between patients with liver injury and no liver injury. The median of AST and ALT of patients requiring blood transfusion was more than that of the patient not requiring blood transfusion(p<0.05). The area under the ROC curve of AST was 0.89(95% Confidence Interval 0.86-0.98) and of ALT was 0.92(95% Confidence Interval 0.83-0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7 %, a specificity of 90 %, a positive predictive value of 86.8 %, and a negative predictive value of 77.6 %. The corresponding values for ALT ≥ 80 U/l were 77.8 %, 94.1%, 92.1% and 82.8 %, respectively. Conclusion: In conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l respectively. The elevated level of AST and ALT might assist the emergency physicians and surgeons to timely refer the suspected patients with the liver injury to a tertiary center.

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