Search results for: acute liver failure

Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Chi V. Phan, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le

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Wilson’s disease is an autosomal recessive disorder of copper metabolism, which is caused by mutation in copper- transporting P-type ATPase (ATP7B). The mechanism of this disease is a failure of hepatic excretion of copper to the bile, and it leads to copper deposits in the liver and other organs. Most clinical symptoms of Wilson’s disease can present as liver disease and/or neurologic disease. Objective: The goal of the study is prenatal diagnosis for pregnant women at high risk of Wilson’s disease in Northern Vietnam. Material and method: Three probands with clinically diagnosed liver disease were detected in the mutations of 21 exons and exon-intron boundaries of the ATP7B gene by direct Sanger-sequencing. Prenatal diagnoses were performed by amniotic fluid sampling from pregnant women in the 16th-18th weeks of pregnancy after the genotypes of parents with the probands were identified. Result: A total of three different mutations of the probands, including of S105*, P1052L, P1273G, were detected. Among three fetuses which underwent prenatal genetic testing, one fetus was homozygote; two fetuses were carriers. Conclusion: Genetic testing provided a useful method for prenatal diagnosis, and is a basis for genetic counseling.

Keywords: ATP7B gene, genetic testing, prenatal diagnosis, pedigree, Wilson disease

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Konja Knüppel, Gerrit Meyer, Peter Nyhuis

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The increasing interconnectedness and complexity of production processes raise the susceptibility of production systems to failure. Therefore, the ability to respond quickly to failures is increasingly becoming a competitive factor. The research project "Sustainable failure management in manufacturing SMEs" is developing a methodology to identify failures in the production and select preventive and reactive measures in order to correct failures and to establish sustainable failure management systems.

Keywords: failure categorization, failure management, logistic performance, production optimization

Procedia PDF Downloads 339

Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Amel A. Refaie, Amal Ramadan, Abdel-Tawab H. Mossa

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This study was designed to evaluate the adverse effects of sub-chronic exposure to the fipronil on the liver of female rats at a dose equal to 400 mg /kg (1/10LD50) in drinking water and the protective role of fish oil at concentration 117.6 mg/Kg b.wt via oral routes daily for 28 days. Fipronil treatment caused a decrease in body weight gain and increase in relative liver weight. Fipronil induced a significant increase in the liver biomarkers enzymes such as alanine aminotransferases (ALT), aspartate aminotransferases (AST), alkaline phosphatase (ALP) and levels of total protein while fipronil caused a significant decrease in butyryl cholinesterase activity in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) were significantly decreased in liver tissue, while lipid peroxidation (LPO) was significantly increased in fipronil treating rats in a dose-dependent manner. FPN caused histopathological alterations in liver of female rats. From our results, it can be reported that FPN induced lipid peroxidation, oxidative stress, liver injury in female rats and fish oil used to protect animals against the adverse effect of pesticide exposure. These pathophysiological alterations in liver tissues could be due to the toxic effect of fipronil that associated with a generation of free radicals.

Keywords: fipronil (FPN), fish oil, hepatotoxicity, transaminases, antioxidant enzymes, female rats

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Authors: Savitri Siddanagoudra, Shantala Herlekar, Priya Arjunwadekar

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Background: The physiological response to water drinking in healthy subjects is an integrated response with an increase in sympathetic vasoconstrictor activity with induced bradycardia. Obesity is a modern pandemic, implicated in the pathogenesis of cardiovascular disease. In autonomic failure patients, water drinking has been shown the increased high blood pressure and bradycardia. Acute effects of ice water ingestion on blood pressure (BP) in relation to body mass index (BMI) is not addressed in literature. Objectives: Objective of this study is to evaluate BP before and after ingestion of cold water in all the three groups. Methods and Material: 60 healthy subjects between the age group of 18-24 yrs were selected and assigned into 3 groups based on BMI. BMI less than and equal to 25 kg/m2 is selected as Normal BMI group ,between 25- 29 kg/m2 as Overweight and BMI more than and equal to 30 kg/m2 as Obese. Procedure: Basal and after ingestion of 250 ml of cold water (7 0C ± 0.5 0C)BP was recorded in all the 3 groups. Results: Basal and after ice water ingestion BP increased statistically in all 3 groups. Conclusion: On acute ingestion of ice water overweight, obese may have more sympathoexcitaion compared to normal subjects.

Keywords: blood pressure, body mass index, ice water, symathoexcitation

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Authors: Manal E. A Elhalwagy, Nadia Amin Abdulmajeed, Hanan S. Alnahdi, Enas N. Danial

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Baron is herbicide includes (48% glyphosate) widely used in Egypt. The present study assesses the cytotoxic and genotoxic effect of baron on rats liver. Two groups of rats were treated orally with 1/10 LD 50, (275.49 mg kg -1) and 1/40 LD 50, (68.86 mg kg-1) glyphosate for 28 days compared with control group. Serum and liver tissues were taken at 14 and 28 days of treatment. An inhibition in Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were recorded at both treatment periods and reduction in total serum protein (TP) and albumin (ALB). However, non-significant changes in serum acetylcholinesterase (AChE). Elevation in oxidative stress biomarker malondyaldehyde (MDA) and the decline in detoxification biomarker total reduced glutathione (GSH), Glutathione S-transferase (GST) and superoxide dismutase (SOD) in liver tissues led to increase in percentage of DNA damage. Destruction in liver tissue architecture was observed . Although, Baron was classified in the safe category pesticides repeated exposure to small doses has great danger effect.

Keywords: glyphosate, liver toxicity, oxidative stress, DNA damage, commet assay

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Chiung-Yun Chang, Po-Chou Chen, Jiun-Shiang Tzeng, Ka-Wai Mac, Chia-Chi Hsiao, Jo-Chi Jao

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This study aimed to measure R2* relaxation rates in the liver of New Zealand White (NZW) rabbits. R2* relaxation rate has been widely used in various hepatic diseases for iron overload by quantifying iron contents in liver. R2* relaxation rate is defined as the reciprocal of T2* relaxation time and mainly depends on the composition of tissue. Different tissues would have different R2* relaxation rates. The signal intensity decay in Magnetic resonance imaging (MRI) may be characterized by R2* relaxation rates. In this study, a 1.5T GE Signa HDxt whole body MR scanner equipped with an 8-channel high resolution knee coil was used to observe R2* values in NZW rabbit’s liver and muscle. Eight healthy NZW rabbits weighted 2 ~ 2.5 kg were recruited. After anesthesia using Zoletil 50 and Rompun 2% mixture, the abdomen of rabbit was landmarked at the center of knee coil to perform 3-plane localizer scan using fast spoiled gradient echo (FSPGR) pulse sequence. Afterward, multi-planar fast gradient echo (MFGR) scans were performed with 8 various echo times (TEs) (2/4/6/8/10/12/14/16 ms) to acquire images for R2* calculations. Regions of interest (ROIs) at liver and muscle were measured using Advantage workstation. Finally, the R2* was obtained by a linear regression of ln(SI) on TE. The results showed that the longer the echo time, the smaller the signal intensity. The R2* values of liver and muscle were 44.8  10.9 s-1 and 37.4  9.5 s-1, respectively. It implies that the iron concentration of liver is higher than that of muscle. In conclusion, R2* is correlated with iron contents in tissue. The correlations between R2* and iron content in NZW rabbit might be valuable for further exploration.

Keywords: liver, magnetic resonance imaging, muscle, R2* relaxation rate

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Authors: Yu Wen Wang, Shyh Ming Kuo, Hsia Ying Cheng, Yu Chiuan Wu

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Liver fibrosis is caused by the activation of hepatic stellate cells in the liver to secrete excessive and deposition of extracellular matrix. In recent years, many treatment strategies have been developed to reduce the activation of hepatic stellate cells and therefore to increase the decomposition of extracellular matrix. Bacopa monnieri, an herbaceous plant of the scrophulariaceae, containing saponins and glycosides, which with antioxidant, anti-inflammation, pain relief and free radical scavenging characteristics. This study was to evaluate the inhibition of hepatic stellate cell activity by Bacopa monnieri extract and its therapeutic potential in treating thioacetamide-induced liver fibrosis in rats. The results showed that the IC50 of Bacopa monnieri extract was 0.39 mg/mL. Bacopa monnieri extract could effectively reduce H2O2-induced hepatic stellate cells inflammation. In the TAA-induced liver fibrosis animal studies, albumin secretion recovered to normal level after treated with Bacopa monnieri extract for 2-w, and fibrosis related proteins, α-SMA and TGF-1levels decreased indicating the extract exerted therapeutic effect on the liver fibrosis. However, inflammatory factors TNF- obviously decreased after 4-w treatment. In summary, we could successfully extract the main component-Bacopaside I from the plant and acquired a potential therapy using this component in treating TAA-induced liver fibrosis in rat.

Keywords: anti-inflammatory, Bacopa monnieri, fibrosis, hepatic stellate cells, water extract

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Authors: Ryan M. Monti, Bijal Mehta

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In cases of massive pulmonary embolism, defined as acute pulmonary embolism presenting with systemic hypotension or right ventricular dysfunction and impending failure, there is indication that unconventional therapies, such as phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs may decrease the morbidity and mortality. Based on the premise that dilating the pulmonary artery will decrease the pulmonary vascular pressure, while simultaneously decreasing the aggregation of platelets, it can be hypothesized that increased blood flow through the pulmonary artery will decrease right heart strain and subsequent morbidity and mortality. While this theory has yet to be formally studied, the recommendations for treating massive pulmonary embolism with phosphodiesterase inhibitors, endothelin receptor antagonists, and/or prostacyclin analogs in conjunction with the current standards of care in massive pulmonary embolism should be formally studied. In particular, patients with massive PE who are unable to undergo thrombolysis/surgical intervention may be the ideal population to study the use of these treatments to determine any decrease in mortality and morbidity (short term and long term).

Keywords: acute pulmonary thromboembolism, treatment of pulmonary embolism, use of phosphodiesterase inhibitors, endothelin receptor antagonists, prostacyclin analogs in PE

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Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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Authors: O. Maranci, A. B. Tugrul

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Scintigraphy is an imaging method of nuclear events provoked by collisions or charged current interactions with radiation. It is used for diagnostic test used in nuclear medicine via radiopharmaceuticals emitting radiation which is captured by gamma cameras to form two-dimensional images. Liver scintigraphy is widely used in nuclear medicine.Tc-99m and Cr-51 gamma radioisotopes can be used for this purpose. Cr-51 usage is more important for patients’ organ dose that has higher energy and longer half-life as compared to Tc-99m. In this study, it is aimed to determine the required dose for critical organs of patient through liver scintigraphy via Cr-51 gamma radioisotope. Experimental studies were conducted on patients even though conducting experimental studies on patients is extremely difficult for determination of critical organ doses. Torso phantom was utilized to simulate the liver scintigraphy by using 20 mini packages of Cr-51 that were placed on the organ. The radioisotope was produced by irradiation in central thimble of TRIGA MARK II Reactor at 250 KW power. As the results of the study, critical organ doses were determined and evaluated with different critic organs.

Keywords: critical organ doses, liver, scintigraphy, TRIGA Mark-II

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Authors: G. Shiha, S. Seif, W. Samir, K. Zalata

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Prospective Validation of the FibroTest Score in assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4 FibroTest (FT) is non-invasive score of liver fibrosis that combines the quantitative results of 5 serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma glutamyl transpeptidase (GGT) and bilirubin) and adjusted with the patient's age and sex in a patented algorithm to generate a measure of fibrosis. FT has been validated in patients with chronic hepatitis C (CHC) (Halfon et al., Gastroenterol. Clin Biol.( 2008), 32 6suppl 1, 22-39). The validation of fibro test ( FT) in genotype IV is not well studied. Our aim was to evaluate the performance of FibroTest in an independent prospective cohort of hepatitis C patients with genotype 4. Subject was 122 patients with CHC. All liver biopsies were scored using METAVIR system. Our fibrosis score(FT) were measured, and the performance of the cut-off score were done using ROC curve. Among patients with advanced fibrosis, the FT was identically matched with the liver biopsy in 18.6%, overestimated the stage of fibrosis in 44.2% and underestimated the stage of fibrosis in 37.7% of cases. Also in patients with no/mild fibrosis, identical matching was detected in 39.2% of cases with overestimation in 48.1% and underestimation in 12.7%. So, the overall results of the test were identical matching, overestimation and underestimation in 32%, 46.7% and 21.3% respectively. Using ROC curve it was found that (FT) at the cut-off point of 0.555 could discriminate early from advanced stages of fibrosis with an area under ROC curve (AUC) of 0.72, sensitivity of 65%, specificity of 69%, PPV of 68%, NPV of 66% and accuracy of 67%. As FibroTest Score overestimates the stage of advanced fibrosis, it should not be considered as a reliable surrogate for liver biopsy in hepatitis C infection with genotype 4.

Keywords: fibrotest, chronic Hepatitis C, genotype 4, liver biopsy

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Authors: Md. Shakhawat Hossain, Jimma Hossain, Md. Naushad Ali

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Acute pancreatitis is a dangerous medical emergency in the practice of gastroenterology. Management of acute pancreatitis needs multidisciplinary approach with support starts from emergency to ICU. So, there is a chance of mismanagement in every steps, especially in low resource settings. Other factors such as patient’s financial condition, education, social custom, transport facility, referral system from periphery may also challenge the current guidelines for management. The present study is intended to determine the clinico-pathological profile, severity assessment and challenges of management of acute pancreatitis in a government laid tertiary care hospital to image the real scenario of management in a low resource place. A total 100 patients of acute pancreatitis were studied in this prospective study, held in the Department of Gastroenterology, Rangpur medical college hospital, Bangladesh from July 2017 to July 2018 within one year. Regarding severity, 85 % of the patients were mild, whereas 13 were moderately severe, and 2 had severe acute pancreatitis according to the revised Atlanta criteria. The most common etiologies of acute pancreatitis in our study were gall stone (15%) and biliary sludge (15%), whereas 54% were idiopathic. The most common challenges we faced were delay in hospital admission (59%) and delay in hospital diagnosis (20%). Others are non-adherence of patient party, and lack of investigation facility, physician’s poor knowledge about current guidelines. We were able to give early aggressive fluid to only 18% of patients as per current guideline. Conclusion: Management of acute pancreatitis as per guideline is challenging when optimum facility is lacking. So, modified guidelines for assessment and management of acute pancreatitis should be prepared for low resource setting.

Keywords: acute pancreatitis, challenges of management, severity, prognosis

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Authors: Roham Rafiee, Hadi Hesamsadat

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In this study, a parametric finite element modeling is developed to analyze failure modes of FRP pipes subjected to internal pressure. First-ply failure pressure and functional failure pressure was determined by a progressive damage modeling and then it is validated using experimental observations. The influence of both winding angle and fiber volume fraction is studied on the functional failure of FRP pipes and it corresponding pressure. It is observed that despite the fact that increasing fiber volume fraction will enhance the mechanical properties, it will be resulted in lower values for functional failure pressure. This shortcoming can be compensated by modifying the winding angle in angle plies of pipe wall structure.

Keywords: composite pipe, functional failure, progressive modeling, winding angle

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Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh

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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.

Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome

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Authors: Lucian Mocan

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We present method of Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinomacell line), using gold nanoparticles combuned with a specific growth factor and demonstrate its selective therapeutic efficacy usig ex vivo specimens. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Ab bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of Ab bound to GNPs into tumor cells following ex-vivo intravascular perfusion. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells, gold nanoparticles, nanoparticle functionalization, laser irradiation

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: hesperidin, cyclophosphamide, liver, rats

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Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

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Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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Authors: Yasuyuki Takahashi, Hayato Ishimura, Masao Miyagawa, Teruhito Mochizuki

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Quantitative measurement of myocardium perfusion is possible with single photon emission computed tomography (SPECT) using a semiconductor detector. However, accumulation of ^99mTc-tetrofosmin in the liver may make it difficult to assess that accurately in the inferior myocardium. Our idea is to reduce the high accumulation in the liver by using dynamic SPECT imaging and a technique called time subtraction. We evaluated the performance of a new SPECT system with a cadmium-zinc-telluride solid-state semi- conductor detector (Discovery NM 530c; GE Healthcare). Our system acquired list-mode raw data over 10 minutes for a typical patient. From the data, ten SPECT images were reconstructed, one for every minute of acquired data. Reconstruction with the semiconductor detector was based on an implementation of a 3-D iterative Bayesian reconstruction algorithm. We studied 20 patients with coronary artery disease (mean age 75.4 ± 12.1 years; range 42-86; 16 males and 4 females). In each subject, 259 MBq of ^99mTc-tetrofosmin was injected intravenously. We performed both a phantom and a clinical study using dynamic SPECT. An approximation to a liver-only image is obtained by reconstructing an image from the early projections during which time the liver accumulation dominates (0.5~2.5 minutes SPECT image-5~10 minutes SPECT image). The extracted liver-only image is then subtracted from a later SPECT image that shows both the liver and the myocardial uptake (5~10 minutes SPECT image-liver-only image). The time subtraction of liver was possible in both a phantom and the clinical study. The visualization of the inferior myocardium was improved. In past reports, higher accumulation in the myocardium due to the overlap of the liver is un-diagnosable. Using our time subtraction method, the image quality of the ^99mTc-tetorofosmin myocardial SPECT image is considerably improved.

Keywords: 99mTc-tetrofosmin, dynamic SPECT, time subtraction, semiconductor detector

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Authors: Kedar S. Prabhavalkar, Nimmy Baby Poovanpallil

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Lamotrigine is approved for maintenance treatment of bipolar I disorder. However, its role in the treatment of acute bipolar depression is not well clear. Its efficacy in the treatment of major depressive disorders including refractory unipolar depression suggested the use of lamotrigine as an augmentation drug for acute bipolar depression. The present study aims to evaluate and perform a comparative analysis of the therapeutic effects of lamotrigine, an epileptic mood stabilizer, when used alone and in combination with duloxetine in treating acute bipolar depression at different doses of lamotrigine. Male swiss albino mice were used. For evaluation of efficacy of combination, immobility period was analyzed 30 min after the treatment from forced swim and tail suspension tests. Further amount of sucrose consumed in sucrose preference test was estimated. The combination of duloxetine and lamotrigine showed potentiation of antidepressant activity in acute models. Decrease in immobility time and increase in the amount of sucrose consumption in stressed mice were higher in combined group compared to lamotrigine monotherapy group. Brain monoamine levels were also attenuated more with combination compared to monotherapy. Results of the present study suggest potential role of lamotrigine and duloxetine combination in the treatment of acute bipolar depression.

Keywords: lamotrigine, duloxetine, acute bipolar depression, augmentation

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Authors: Don Buddika Oshadi Malaweera, Lora Harris, Bruce Rathgeber, Chibuike C. Udenigwe, Kirsti Rouvinen-Watt

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Fatty liver disease is among the three most severe health concerns for mink and believed to occur through the same mechanism as nursing sickness. In North America, nursing sickness affects about 45% of mink farms and in Canada, approximately 50,000 mink females is affected annually. Orotic acid (OA) plays a critical role in lipid metabolism and can increase hepatic lipids by enhancing Sterol regulatory element binding protein-1c expression and decreasing Carnitine palmitoyl transferase I activity. This study was conducted to identify particular pathways and regulatory control points involved in fatty liver development, and evaluate the effectiveness of arginine and bioactive peptides for prevention and treatment of fatty liver disease in mink. A total of 45 mink were used in 9 treatments. The experimental diets consisted of 1% OA, 2% L-arginine and 5% of whey protein hydrolysates. At the end of 10 days of experimental period, the mink were anaesthetized, sampled for blood and euthanized, samples were obtained for histological, biochemical and molecular assays. The blood samples will be analyzed for clinical chemistry and triacylglycerol. The liver samples will be analyzed for total lipid content and analyzed for 6 genes of interest involved in adipogenic transformation, ER stress, and liver inflammation.

Keywords: fatty liver, L-arginine, mink, orotic acid, whey protein hydrolysates

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Authors: S. H. Atef, N. H. Mahmoud, S. Abdrahman, A. Fattoh

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Background: The aim of the study is to assess the diagnostic value of fibrotest and hyaluronic acid in discriminate between insignificant and significant fibrosis. Also, to find out if these parameters could replace liver biopsy which is currently used for selection of chronic hepatitis C patients eligible for antiviral therapy. Study design: This study was conducted on 52 patients with HCV RNA detected by polymerase chain reaction (PCR) who had undergone liver biopsy and attending the internal medicine clinic at Ain Shams University Hospital. Liver fibrosis was evaluated according to the METAVIR scoring system on a scale of F0 to F4. Biochemical markers assessed were: alpha-2 macroglobulin (α2-MG), apolipoprotein A1 (Apo-A1), haptoglobin, gamma-glutamyl transferase (GGT), total bilirubin (TB) and hyaluronic acid (HA). The fibrotest score was computed after adjusting for age and gender. Predictive values and ROC curves were used to assess the accuracy of fibrotest and HA results. Results: For fibrotest, the observed area under curve for the discrimination between minimal or no fibrosis (F0-F1) and significant fibrosis (F2-F4) was 0.6736 for cutoff value 0.19 with sensitivity of 84.2% and specificity of 85.7%. For HA, the sensitivity was 89.5% and specificity was 85.7% and area under curve was 0.540 at the best cutoff value 71 mg/dL. Multi-use of both parameters, HA at 71 mg/dL with fibrotest score at 0.22 give a sensitivity 89.5%, specificity 100 and efficacy 92.3% (AUC 0.895). Conclusion: The use of both fibrotest score and HA could be as alternative to biopsy in most patients with chronic hepaitis C putting in consideration some limitations of the proposed markers in evaluating liver fibrosis.

Keywords: fibrotest, liver fibrosis, HCV RNA, biochemical markers

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Authors: Sherif Refaat, Hassan Aref

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Background: Although asthma is a well-identified presentation to the emergency department, little is known about the frequency and percentage of respiratory and non-respiratory symptoms in patients with acute asthma in the emergency department (ED). Objective: The aim of this study is to identify the relationship between acute asthma exacerbation and different respiratory and non-respiratory symptoms including chest pain encountered by patients visiting the emergency department. Subjects and methods: Prospective study included 169 (97 females and 72 males) asthmatic patients who were admitted to emergency department of two tertiary care facility hospitals for asthma exacerbation from the period of September 2010 to August 2013, an anonyms questionnaire was used to collect symptoms and analysis of symptoms. Results: Females were 97 (57%) of the patients, mean age was 35.6 years; dyspnea on exertion was the commonest symptom accounting for 161 (95.2%) of patients, followed by dyspnea at rest 155 (91.7%), wheezing in 152 (89.9%), chest pain was present in 82 patients (48.5%), the pain was burning in 36 (43.9%) of the total patients with chest pain. Non-respiratory symptoms were seen frequently in acute asthma in ED. Conclusions: Dyspnea was the commonest chest symptoms encountered in patients with acute asthma followed by wheezing. Chest pain in acute asthma is a common symptom and should be fully studied to exclude misdiagnosis as of cardiac origin; there is a need for a better dissemination of knowledge about this disease association with chest pain. It was also noted that other non-respiratory symptoms are frequently encountered with acute asthma in emergency department.

Keywords: asthma, emergency department, respiratory symptoms, non respiratory system

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Authors: Maria Medeiros, Suren Surenthiran, Abitha Muralithar, Soushma Seeburuth, Mohammed Mohammed

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Introduction: Appendicitis is the most common surgical emergency globally and can have devastating consequences. Diagnostic imaging in acute appendicitis has become increasingly common in aiding the diagnosis of acute appendicitis. Computerized tomography (CT) and ultrasound (US) are the most commonly used imaging modalities for diagnosing acute appendicitis. Pre-operative imaging has contributed to a reduction of negative appendicectomy rates from between 10-29% to 5%. Literature report CT scan has a diagnostic sensitivity of 94% in acute appendicitis. This clinical audit was conducted to establish if the CT scan's diagnostic yield for acute appendicitis matches the literature. CT scan has a high sensitivity and specificity for diagnosing acute appendicitis and its use can result in a lower negative appendicectomy rate. The aim of this study is to compare the pre-operative imaging findings from CT scans to the histopathology results post-operatively and establish the accuracy of CT scans in aiding the diagnosis of acute appendicitis. Methods: This was a retrospective study focusing on adult presentations to the general surgery department in a district general hospital in central London with an impression of acute appendicitis. We analyzed all patients from July 2022 to December 2022 who underwent a CT scan preceding appendicectomy. Pre-operative CT findings and post-operative histopathology findings were compared to establish the efficacy of CT scans in diagnosing acute appendicitis. Our results were also cross-referenced with pre-existing literature. Data was collected and anonymized using CERNER and analyzed in Microsoft Excel. Exclusion criteria: Children, age <16. Results: 65 patients had CT scans in which the report stated acute appendicitis. Of those 65 patients, 62 patients underwent diagnostic laparoscopies. 100% of patients who underwent an appendicectomy with a pre-operative CT scan showing acute appendicitis had acute appendicitis in histopathology analysis. 3 of the 65 patients who had a CT scan showing appendicitis received conservative treatment. Conclusion: CT scans positive for acute appendicitis had 100% sensitivity and a positive predictive value, which matches published research studies (sensitivity of 94%). The use of CT scans in the diagnostic work-up for acute appendicitis can be extremely helpful in a) confirming the diagnosis and b) reducing the rates of negative appendicectomies and consequently reducing unnecessary operative-associated risks for patients, reducing costs and reducing pressure on emergency theatre lists.

Keywords: acute apendicitis, CT scan, general surgery, imaging

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Authors: Nuseiba M. Altarawneh, Suhuai Luo, Brian Regan, Guijin Tang

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Liver segmentation from medical images poses more challenges than analogous segmentations of other organs. This contribution introduces a liver segmentation method from a series of computer tomography images. Overall, we present a novel method for segmenting liver by coupling density matching with shape priors. Density matching signifies a tracking method which operates via maximizing the Bhattacharyya similarity measure between the photometric distribution from an estimated image region and a model photometric distribution. Density matching controls the direction of the evolution process and slows down the evolving contour in regions with weak edges. The shape prior improves the robustness of density matching and discourages the evolving contour from exceeding liver’s boundaries at regions with weak boundaries. The model is implemented using a modified distance regularized level set (DRLS) model. The experimental results show that the method achieves a satisfactory result. By comparing with the original DRLS model, it is evident that the proposed model herein is more effective in addressing the over segmentation problem. Finally, we gauge our performance of our model against matrices comprising of accuracy, sensitivity and specificity.

Keywords: Bhattacharyya distance, distance regularized level set (DRLS) model, liver segmentation, level set method

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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Authors: S. W. Liu, J. H. Lv, W. Z. Wang

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In recent years, the failure accidents in petrochemical industry have been frequent, and have posed great security problems in personnel and property. The improvement of petrochemical safety is highly requested in order to prevent re-occurrence of severe accident. This study focuses on surveying the failure cases occurred in petrochemical field, which were extracted from journals of engineering failure, including engineering failure analysis and case studies in engineering failure analysis. The relation of failure mode, failure mechanism, type of components, and type of materials was analyzed in this study. And the analytical results showed that failures occurred more frequently in vessels and piping among the petrochemical equipment. Moreover, equipment made of carbon steel and stainless steel accounts for the majority of failures compared to other materials. This may be related to the application of the equipment and the performance of the material. In addition, corrosion failures were the largest in number of occurrence in the failure of petrochemical equipment, in which stress corrosion cracking accounts for a large proportion. This may have a lot to do with the service environment of the petrochemical equipment. Therefore, it can be concluded that the corrosion prevention of petrochemical equipment is particularly important.

Keywords: cases analysis, corrosion, failure, petrochemical industry

Procedia PDF Downloads 271