scholarly journals Diffusion Tensor Imaging Quantifying the Severity of Chronic Hepatitis in Rats

2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu

Abstract Background: Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. DTI was applied to assess fiber in liver disorders in previous studies. However, the data obtained have been insufficient in determining if DTI can be used to exactly stage chronic hepatitis. This study assessed the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A) and steatosis (S) with chronic hepatitis in rats. Methods: Seventy male Sprague-Dawley rats were divided into a control group(n=10) and an experimental group(n=60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All of the rats underwent 3.0T MRI. Regions of interest (ROIs) were subjected to DTI to estimate the MR parameters (rADC value and FA value). Histopathology was used as the reference standard. Multiple linear regression was used to analyze the associations between the MR parameters and pathology. The differences in the MR parameters among the pathological stages were evaluated by MANOVA or ANOVA. The LSD test was used to test for differences between each pair of groups. ROC analysis was also performed. Results: The count of each pathology was as follows: F0(n=15), F1(n=11), F2(n=6), F3(n=9), F4(n=6); A0(n=8), A1(n=16), A2(n=16), A3(n=7); S0(n=10), S1(n=7), S2(n=3), S3(n=11), S4(n=16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P=0.008) and inflammation (r=-0.359, P=0.015). The FA value had a positive correlation with fibrosis (r=0.409, P=0.005). Significant differences were found in the FA values between F4 and F0~F3 (P=0.03), while no significant differences among F0~F3 were found (P> 0.05). The AUC of the FA value differentiating F4 from F0~F3 was 0.909 (p<0.001) with an 83.3% sensitivity and an 85.4% specificity when the FA value was at the cut-off of 588.089 (×10-6mm2/s).Conclusion: The FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis, but the rADC value lacked the ability to differentiate among the fibrotic grades. Both the FA and rADC values were unable to discriminate the stages of necroinflammatory activity and steatosis.


2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.



2020 ◽  
Vol 48 (8) ◽  
pp. 965-980
Author(s):  
Robert C. Sills ◽  
G. Allan Johnson ◽  
Robert J. Anderson ◽  
Crystal L. Johnson ◽  
Michael Staup ◽  
...  

It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with magnetic resonance microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.



2008 ◽  
Vol 28 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Bachir Taouli ◽  
Malik Chouli ◽  
Alastair J. Martin ◽  
Aliya Qayyum ◽  
Fergus V. Coakley ◽  
...  


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Nanik Sundari ◽  
Vivian Soetikno ◽  
Melva Louisa ◽  
Bantari W. Wardhani ◽  
Raymond R. Tjandrawinata

Phaleria macrocarpais one of the Indonesian herbal plants which has been shown to have a hepatoprotective effect. This study was conducted to evaluate the protective effect of water extract of mahkota dewa (Phaleria macrocarpa) in liver fibrosis and to elucidate its mechanism of action. Male Sprague-Dawley rats were treated with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis. Rats were randomly divided into 6 groups (n=5), i.e., control group, CCl4 group, CCl4 + NAC group, CCl4 + various doses of water extract ofPhaleria macrocarpa(50, 100, and 150 mg/kg body weight). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor- (TNF-)α, and Transforming Growth Factor- (TGF-)β1were analyzed.This study demonstrated that water extract ofPhaleria macrocarpaand NAC significantly protected CCl4-induced liver injury as demonstrated by reduced AST, ALT, ALP, and fibrosis percentage compared with the CCl4-only group. In addition, water extract ofPhaleria macrocarpaand NAC significantly reduced the levels of MDA, TNF-α, and TGF-β1as well as increasing the ratio of GSH/GSSG. Water extract ofPhaleria macrocarpaprevents CCl4-induced fibrosis in rats. The prevention of liver fibrosis was at least in part through its antioxidant and anti-inflammatory activities and through its capacity to inhibit hepatic stellate cells (HSC) activation by reducing fibrogenic cytokine TGF-β1.



Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.



2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.



Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.



QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Marcel William Keddeas ◽  
Hany Haroun Kaisar ◽  
Hagar Ahmed Ahmed Elessawy ◽  
Mariam Samir Abdel Hamid Elewa

Abstract Background and aim Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum diagnostic marker for liver fibrosis in various liver diseases. We aimed to evaluate its role in assessment of liver fibrosis in chronic hepatitis B infection (CHB) with reference to liver stiffness measurement (LSM) by transient elastography (Fibroscan). Design and Methods A case control study. 50 CHB patients with LSM by transient elastography technology and retrievable serum samples and 20 normal volunteers as a control group were recruited. Results 50 CHB patients (M: F = 30:20; mean age 43years ± 10.58) and 20 normal control volunteers (M: F = 12:8; mean age 37years ± 14.5) were recruited. The mean M2BPGi values for control group, F0-F1, F2, F3 and F4 progressively increased with more advanced stages of liver fibrosis: 0.282, 0.719, 1.322, 1.65 and 1.904 COI, respectively (p &lt; 0.001). M2BPGi levels correlated well with liver stiffness (r = 0.911) and moderately with FIB-4 (r = 0.682), and with APRI (r = 0.536) (all p &lt; 0.001). Using cut-off values of 0.455, 1.02, 1.16, 1.66 and 1.71COI for control, F0-F1, F2, F3 and F4 groups, respectively, the AUROCs were 0.996, 0.996, 0.691, 0.794 and 1.00 for control, F0-F1, F2, F3 and F4 groups, respectively. There was a statistically significant but with weak positive correlation between M2BPGi serum level and INR (r = 0.333, p = 0.018). And there was a statistically significant but with weak negative correlation between M2BPGi serum level and platelet count (r = -0.41, p = 0.003) and HBV DNA (r = -0.373, p = 0.008).There was a statistically significance between M2BPGi serum level and the history of varices (p = 0.023) Conclusions WFA+-M2BP is an accurate serum indicator for assessing different stages of liver fibrosis. WFA+-M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan.



2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.



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