Search results for: acute liver injury

Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

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Authors: JiYoung Park, SueGoo Rhee, HyunAe Woo

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In liver regeneration, quiescent hepatocytes need to be primed to fully respond to growth factors such as hepatocyte growth factor. To understand the priming process, it is necessary to analyze patterns of gene expression that occur during liver regeneration after partial hepatectomy (PHx). Recently, tyrosine phosphorylation of signal transducer and activator of transcription 3 (pYSTAT3) has been shown to play an important role in initiating liver regeneration. In order to evaluate the role of pYSTAT3 on liver regeneration after PHx, we used an intrabody which can selectively inhibit pYSTAT3. In our previous studies, an intrabody had been shown that it bound specifically to the pYSTAT3. Adenovirus-mediated expression of the intrabody in HepG2 cells, as well as mouse liver, blocked both accumulation of pYSTAT3 in the nucleus and downstream target of pYSTAT3. In this study, PHx was performed on intrabody-expressing mice and the expression levels of liver regeneration-related genes were analyzed. We also measured liver/body weight ratios and the related cellular signaling pathways were analyzed. Acute phase response genes were reduced in an intrabody-expressing mice during liver regeneration than in control virus-injected mice. However, the time course of liver mass restoration in intrabody-expressing mice was similar to that observed in control virus-injected mice. We also observed that the expression levels of anti-apoptotic genes, such as Bcl2 and Bcl-xL were decreased in intrabody-expressing mice whereas the expression of cell cycle-related genes such as cyclin D1, and c-myc was increased. Liver regeneration after PHx was partially impaired by the selective inhibition of pYSTAT3 with a phosphorylation site-specific intrabody and these results indicated that pYSTAT3 might have limited role in liver mass recovery.

Keywords: STAT3, pYSTAT3, liver regeneration, intrabody

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Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub

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This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.

Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Kamyar Moradi

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Background: Acute mesenteric ischemia is known as a life-threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury, which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. Methods: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg, and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 minutes followed by 120 minutes of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also, protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. Results: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. Conclusion: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. Still, more studies would clarify existing causality in this phenomenon.

Keywords: albendazole, ischemia reperfusion injury, inflammation, mesenteric ischemia

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Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: S. Shafiee Ardestani, A. Najafi, N. Valizadeh, E. Payani, H. Karimian

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Objectives: Treatment of mild traumatic brain injury in emergency ward patients with any type of traumatic intracranial hemorrhage is flexible. The aim of this study is to assess the clinical outcomes of mild traumatic brain injury patients who had acute traumatic intracranial hemorrhage on initial emergency ward neuroimaging. Materials-Methods: From March 2011 to November 2012 in a retrospective cohort study we enrolled emergency ward patients with mild traumatic brain injury with Glasgow Coma Scale (GCS) scores of 14 or 15 and who had stable vital signs. Patients who had any type of intracranial hemorrhage on first head CT and repeat head CT within 24 hours were included. Patients with initial GCS < 14, injury > 24 hours old, pregnancy, concomitant non-minor injuries, and coagulopathy were excluded. Primary endpoints were neurosurgical procedures and/or death and for discharged patients, return to the emergency ward during one week. Results: Among 755 patients who were referred to the emergency ward and underwent two head CTs during first 24 hours, 302 (40%) were included. The median interval between CT scans was 6 hours (ranging 4 to 8 hours). Consequently, 135 (45%) patients had subarachnoid hemorrhage, 124 (41%) patients had subdural hemorrhage, 15 (5%) patients had epidural hemorrhage, 28 (9%) patients had cerebral contusions, and 54 (18%) patients had intra-parenchymal hemorrhage. Six of 302 patients died within 15 days of injury. 200 patients (66%) have been discharged from the emergency ward, 25 (12%) of whom returned to the emergency ward after one week. Conclusion: Discharge of the head trauma patients after a repeat head CT and brief period of observation in the emergency ward lead to early discharge of mild traumatic brain injury patients with traumatic ICH without adverse events.

Keywords: clinical outcomes, emergency ward, mild traumatic intracranial hemorrhage, Glasgow Coma Scale (GCS)

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Authors: Michelle Roesler, Ian Glendon, Francis O'Callaghan

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This study expands on recent findings and offers a new perspective on recovery from injury and return to work (RTW) after an acute traumatic occupational hand injury. Recovery is a complex medical and psychosocial process. A number of predictor variables were studied simultaneously to identify the bio-psychosocial variables that impede recovery. An unexpected phenomenon to emerge from this study was the high incidence of complications within the hand-injured patient sample. Twenty six percent (n = 71) of the total sample (N = 263) required a second operation due to complications. This warranted further investigation. Results confirmed that complications not only significantly delayed the RTW outcome but also had a profound psychological impact on the individuals affected. Research has found that surgical complications are usually the result of incorrect early assessment and management. A strategic plan needs to be implemented to ensure the optimal level of surgical care is provided for managing acute traumatic hand injuries to avoid such complications.

Keywords: occupational hand trauma, psychological recovery, return to work, psychology

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Authors: Alakija Temitope Olufunmilayo, Akinyemi, Yagba Joy

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Hepatitis is the inflammation of the liver tissue that can cause whiteness of the eyes (Jaundice), lack of appetite, vomiting, tiredness, abdominal pain, diarrhea. Hepatitis is acute if it resolves within 6 months and chronic if it last longer than 6 months. Acute hepatitis can resolve on its own, lead to chronic hepatitis or rarely result in acute liver failure. Chronic hepatitis may lead to scarring of the liver (Cirrhosis), liver failure and liver cancer. Modelling Hepatitis B may become necessary in order to reduce its spread. So, dynamic SIR model can be used. This model consists of a system of three coupled non-linear ordinary differential equation which does not have an explicit formula solution. It is an epidemiological model used to predict the dynamics of infectious disease by categorizing the population into three possible compartments. In this study, a five-compartment dynamic model of Hepatitis B disease was proposed and developed by adding control measure of sensitizing the public called awareness. All the mathematical and statistical formulation of the model, especially the general equilibrium of the model, was derived, including the nonlinear least square estimators. The initial parameters of the model were derived using nonlinear least square embedded in R code. The result study shows that the proportion of Hepatitis B patient in the study population is 1.4 per 1,000,000 populations. The estimated Hepatitis B induced death rate is 0.0108, meaning that 1.08% of the infected individuals die of the disease. The reproduction number of Hepatitis B diseases in Nigeria is 6.0, meaning that one individual can infect more than 6.0 people. The effect of sensitizing the public on the basic reproduction number is significant as the reproduction number is reduced. The study therefore recommends that programme should be designed by government and non-governmental organization to sensitize the entire Nigeria population in order to reduce cases of Hepatitis B disease among the citizens.

Keywords: hepatitis B, modelling, non-linear ordinary differential equation, sihar model, sensitization

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Authors: Mohamed Bakry Mohamed Ali, Mohamed Ehab El-Din Mustafa, Joseph Naiem Sabet Aziz, Sarah Mahmoud Ali Kaooh

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Background: Acute lung injury (ALI) is one of the major challenges in intensive care medicine. The most common extrapulmonary cause of ALI is sepsis, accounting more than 30% of the cases in humans. Lipopolysaccharide (LPS) has gained wide acceptance as a clinically relevant model of ALI. Lipopolysaccharide is a glycoprotein forming the major constituent of bacterial endotoxin. Losartan is angiotensin II type 1 (AT1) receptor antagonists. It is widely used for management of hypertension. It was recently suggested that losartan protects against septic ALI. It would thereby prevent LPS-induced ALI. Aim of the work and design of the experiment: This work investigated the injurious effect of lipopolysaccharide (LPS) and ALI on adult male albino rat at 24 hours and 14 days of LPS administration and the possible protective role of losartan pretreatment. LPS has deteriorated animal survival and behavior. It increased lung weight and induced lung histological damage. These changes could be much reduced by the losartan pretreatment. Conclusion: Administration of losartan before LPS could largely reduce these LPS/ ALI induced short and long term alterations. It could be recommended that patients susceptible to developing ALI, as in ICU, should receive a protective dose of angitensin II type 1 (AT1) receptor blocker as losartan.

Keywords: acute lung injury (ALI), lipopolysaccharide (LPS), losartan

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Authors: Priya Bajaj, Baby Tabassum

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Arsenic is a poisonous metalloid, naturally occurring in soil, air, rocks and ground water. This dreadful metalloid commonly exists as inorganic compound, arsenic trioxide. WHO permitted maximum limit for arsenic in water is 0.01 mg/L, but some affected areas show ground water level of arsenic up to 3 mg/L even. Ground water arsenic pollution has created a number of health problems, viz. keratosis, melanosis, lesions and even skin cancers. The key objective of our nested study was to characterize arsenic induced hepatotoxicity and to find out some herbal protection against it. For the purpose, we selected albino rat (Rattus norvegicus) as model for arsenic induced liver injury and wild turmeric (Curcuma aromatica) leaf extract as remedy for it. The study was performed at acute (1 day) and subacute (7, 14 & 21 days) levels. The LD50 estimated for arsenic trioxide was 14.98 mg/kg body weight. In our investigation, we observed a significant restoration of altered hepatic lipid, cholesterol, protein and glycogen contents as well as liver weight, body-weight and hepato-somatic index by Curcuma aromatica leaf extract before arsenic intoxication. The results reveal excellent protective efficacy of Curcuma aromatica leaf extract that further can be exploited in remediation programme in heavy metal affected areas.

Keywords: arsenic, Curcuma aromatica, glycogen, lipids

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Authors: Salim Cerig, Fatime Geyikoglu, Murat Bakir, Suat Colak, Merve Sonmez, Kubra Koc

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Cisplatin (CIS) is one of the most effective an anticancer drug and also toxic to cells by activating oxidative stress. Oleuropein (OLE) has key role against oxidative stress in mammalian cells, but the role of this antioxidant in the toxicity of CIS remains unknown. The aim of the present study was to investigate the efficacy of OLE on CIS-induced liver damages in male rats. With this aim, male Sprague Dawley rats were randomly assigned to one of eight groups: Control group; the group treated with 7 mg/kg/day CIS; the groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and the groups treated with OLE for three days starting at 24 h following CIS injection. After 4 days of injections, serum was provided to assess the blood AST, ALT and LDH values. The liver tissues were removed for histological, biochemical (TAC, TOS and MDA) and genotoxic evaluations. In the CIS treated group, the whole liver tissue showed significant histological changes. Also, CIS significantly increased both the incidence of oxidative stress and the induction of 8-hydroxy-deoxyguanosine (8-OH-dG). Moreover, the rats taking CIS have abnormal results on liver function tests. However, these parameters reached to the normal range after administration of OLE for 3 days. Finally, OLE demonstrated an acceptable high potential and was effective in attenuating CIS-induced liver injury. In this trial, the 200 mg/kg dose of OLE firstly appeared to induce the most optimal protective response.

Keywords: antioxidant response, cisplatin, histology, liver, oleuropein, 8-OhdG

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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: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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Authors: Sara Ataei, Maryam Taghizadeh-Ghehi, Amir Sarayani, Asieh Ashouri, Amirhossein Moslehi, Molouk Hadjibabaie, Kheirollah Gholami

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Background: Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. Methods: We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, -3, +3, +9 and +15. Results: Time-dependent Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR=1.04 (1.008-1.07), P=0.01). There was a relation between uNGAL day +9 to baseline ratio and incidence of AKI (unadjusted HR=.1.047(1.012-1.083), P<0.01). The area under the receiver-operating characteristic curve for day +9 to baseline ratio was 0.86 (0.74-0.99, P<0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Conclusions: Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum creatinine rises by nearly 2 days.

Keywords: acute kidney injury, hemtopoietic stem cell transplantation, neutrophil gelatinase-associated lipocalin, Receiver-operating characteristic curve

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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: Uchenna Nkiruka Umeononihu, Adenike Kuku, Oludele Odekanyin, Olubunmi Babalola, Femi Agboola, Rapheal Okonji

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In this study, a lectin from the bulb of Dioscorea bulbifera was purified, characterised, and its acute and sub-acute toxicity was investigated with a view to evaluate its toxic effects in mice. The protein from the bulb was extracted by homogenising 50 g of the bulb in 500 ml of phosphate buffered saline (0.025 M) of pH 7.2, stirred for 3 hr, and centrifuged at the speed of 3000 rpm. Blood group and sugar specificity assays of the crude extract were determined. The lectin was purified in a two-step procedure- gel filtration on Sephadex G-75 and affinity chromatography on Sepharose 4-B arabinose. The degree of purity of the purified lectin was ascertained by SDS-polyacrylamide gel electrophoresis. Detection of covalently bound carbohydrate was carried out with Periodic Acid-Schiffs (PAS) reagent staining technique. Effects of temperature, pH, and EDTA on the lectin were carried out using standard methods. This was followed by acute toxicity studies via oral and subcutaneous routes using mice. The animals were monitored for mortality and signs of toxicity. The sub-acute toxicity studies were carried out using rats. Different concentrations of the lectin were administered twice daily for 5 days via the subcutaneous route. The animals were sacrificed on the sixth day; blood samples and liver tissues were collected. Biochemical assays (determination of total protein, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), catalase (CAT), and superoxide dismutase (SOD)) were carried out on the serum and liver homogenates. The collected organs (heart, liver, kidney, and spleen) were subjected to histopathological analysis. The results showed that lectin from the bulbs of Dioscorea bulbifera agglutinated non-specifically the erythrocytes of the human ABO system as well as rabbit erythrocytes. The haemagglutinating activity was strongly inhibited by arabinose and dulcitol with minimum inhibitory concentrations of 0.781 and 6.25, respectively. The lectin was purified to homogeneity with native and subunit molecular weights of 56,273 and 29,373 Daltons, respectively. The lectin was thermostable up to 30 0C and lost 25 %, 33.3 %, and 100 % of its heamagglutinating activity at 40°C, 50°C, and 60°C, respectively. The lectin was maximally active at pH 4 and 5 but lost its total activity at pH eight, while EDTA (10 mM) had no effect on its haemagglutinating activity. PAS reagent staining showed that the lectin was not a glycoprotein. The sub-acute studies on rats showed elevated levels of ALT, AST, serum bilirubin, total protein in serum and liver homogenates suggesting damage to liver and spleen. The study concluded that the aerial bulb of D. bulbifera lectin was non-specific in its heamagglutinating activity and dimeric in its structure. The lectin shared some physicochemical characteristics with lectins from other Dioscorecea species and was moderately toxic to the liver and spleen of treated animals.

Keywords: Dioscorea bulbifera, heamagglutinin, lectin, toxicity

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Authors: Le Nguyen Binh, Luong Xuan Binh, Le Van Tuan, Tran Binh Duong, Truong Nguyen Khanh Hung, Do Le Hoang Son, Pham Quang Vinh, Hoang Quoc Huy, Nguyen Bach, Nguyen Quoc Khanh Le, Jiunn Horng Kang

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Introduction: Traumatic hip dislocation is an emergency in young adult which can cause avascular necrosis of femoral head or osteoarthritis of hip joint. The reasons for these may be the loose body of bony or chondral fragments, which are difficult to be detected on CT scan or MRI. In those cases, Hip arthroscopy may be the method of choice for diagnosis and treatment of loose bodies in hip joint after traumatic dislocation. Methods: A case report is performed. A 55-year-old male patient was under hip arthroscopy to retrieve the loose body in the right hip joint. Results: The patient’s hip was reduced under anesthesia in the opeation room. Xray and CT scan post-reduction showed that his right hip was wide and a small fragment of femoral head (< 5mm) locking inside the joint. A hip arthroscopy was done to take the fragment out. Post-operation, the patient went under rehabilition. After 6 months, he can walk with full-weight bearing; no further dislocaion was noted, and the Harris score was 84 points. Conclusions: Although acute traumatic injury of hip joint is usually treated with open surgeries, these methods have many drawbacks, such as soft tissue destruction, blood-loss,….Despite its technical requirement, hip arthroscopy is less invasive and effective treatment. Therefore, it may be an alternative treatment for a traumatic hip injury and can be applied frequently in the near future.

Keywords: hip dislocation, hip arthroscopy, hip osteoarthritis, acute hip trauma

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Authors: Youssef. K. A. Abdalhafid, Ezaldin A. M. Mohammed, Masoud M. M. Zatout

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This study described the changes in the liver of Uromastyx acanthinura (Bell, 1825) males and females during hibernation and activity seasons. The results revealed that, hibernation causes increase fatty liver and pigment cells with abundant damage, comparing with nearly normal structure and less fatty liver after the hibernation with almost normal pattern. Genomic DNA showed apparent separation during hibernation. Also, caspase 3 and caspase 7 activity reached a high level in the liver tissue during hibernation comparing with activity season.

Keywords: histological liver, DNA fragmentation, hibernation, caspase 3 and caspase 7

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Authors: Dina Muharib

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Specific metabolic challenges are present following spinal cord injury. The acute stage is characterized by a reduction in metabolic activity, as well as a negative nitrogen balance that cannot be corrected, even with aggressive nutritional support. Metabolic demands need to be accurately monitored to avoid overfeeding. Enteral feeding is the optimal route following SCI. When oral feeding is not possible, nasogastric, followed by nasojejunal, then by percutaneous endoscopic gastrostomy, if necessary, is suggested.

Keywords: SCI, energy, protein, nutrition assessment, eneral feeding, nitrogen balance

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Authors: Seema Chopra, Amandeep Kaur, Vanita Suri, Shalini Gainder, Minakshi Rohilla

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Background: Acute kidney injury (AKI) associated with pregnancy is a serious medical complication which can lead to significant maternal as well as perinatal morbidity and mortality. Material and methods: This prospective observational study was carried out in the Obstetrics and Gynaecology department and dialysis unit of Nephrology department of PGIMER, Chandigarh from July 2013 to June 2014. Forty antenatal/postnatal/postabortal patients who fulfilled the AKIN criteria were enrolled in the study. All patients were followed up till 3 months postpartum. Results: Majority of the patients 23/40 (57.5%) with AKI presented in postpartum period, 14/40 (35%) developed AKI in antenatal period, and 3/40 (7.5%) were postabortal. AKI was attributable mostly to sepsis in 11/40 (27.5%) and PPH in 5/40 (12.5%). Hypertension and its complications causing AKI included eclampsia in 5/40 (12.5%) followed by 3/40 (7.5%) as HELLP syndrome and abruption placentae in 2/40(5%) patients. Three patients each (7.5%) had AFLP, TMA, and HEV as the cause of AKI. Renal replacement therapy in the form of hemodialysis was the treatment in majority of them (28 (70%)). After the acute event, 25 (62.5%) had complete recovery of their renal functions at 3 months follow up. Maternal mortality was seen in 25% (n=10) of the study patients. Conclusion: Timely initiation of RRT in patients with AKI associated with pregnancy has a good maternal outcome in the form of complete recovery of renal functions in 62.5% (25/40) of patients.

Keywords: AKI, dialysis, hypertension, sepsis, renal parameters

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Authors: Sophia Shi

Abstract:

Acute kidney injury (AKI) is the sudden onset of kidney damage in which the kidneys cannot filter waste from the blood, requiring emergency hospitalization. AKI patient mortality rate is high in the ICU and is virtually impossible for doctors to predict because it is so unexpected. Currently, there is no hybrid model predicting AKI that takes advantage of two types of data. De-identified patient data from the MIMIC-III database and de-identified kidney images and corresponding patient records from the Beijing Hospital of the Ministry of Health were collected. Using data features including serum creatinine among others, two numeric models using MIMIC and Beijing Hospital data were built, and with the hospital ultrasounds, an image-only model was built. Convolutional neural networks (CNN) were used, VGG and Resnet for numeric data and Resnet for image data, and they were combined into a hybrid model by concatenating feature maps of both types of models to create a new input. This input enters another CNN block and then two fully connected layers, ending in a binary output after running through Softmax and additional code. The hybrid model successfully predicted AKI and the highest AUROC of the model was 0.953, achieving an accuracy of 90% and F1-score of 0.91. This model can be implemented into urgent clinical settings such as the ICU and aid doctors by assessing the risk of AKI shortly after the patient’s admission to the ICU, so that doctors can take preventative measures and diminish mortality risks and severe kidney damage.

Keywords: Acute kidney injury, Convolutional neural network, Hybrid deep learning, Patient record data, ResNet, Ultrasound kidney images, VGG

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Authors: G. E. Forcados, M. L. Shu, C. N. Chinyere

Abstract:

Acalypha wilkesiana is a medicinal plant commonly used in most parts of West Africa as a decoction in treating several human diseases. Existing literature on its toxicity is predominantly on the organic extracts in contrast to the routine use of hot aqueous extracts as decoction. The aim of this study was to examine the phytochemical profile and sub-acute toxicity of A. wilkesiana leaf extracts in albino rats. Three groups of 8 experimental rats each were administered 300 mg/kg, 600 mg/kg and 1200 mg/kg body weight per day for 14 days while a fourth (control) group took tap-water. On day 15, the rats were sacrificed, and blood collected. Biochemical and hematological parameters were analysed and histopathological examination of liver and kidney were performed. There was significant increase (p<0.05) in the levels of some biochemical parameters (AST, ALT, creatinine, urea) in all the test groups compared to control. Histopathological examination of the liver revealed centrilobular degeneration and necrosis with sinusoidal dilatation as well as polymorphonuclear and mononuclear infiltration, likewise severe glomerular and tubular degeneration and necrosis with hemorrhage in the kidney at all dose levels. The results from this study suggest that aqueous leaf extract of A. wilkesiana is hepatotoxic and nephrotoxic at dose levels of 300 mg/kg and above. Therefore, precautionary measures are necessary for home use of the leaf extract of A. wilkesiana.

Keywords: acute toxicity, A. wilkesiana, aqeous extract, albino rats, biochemical and haematological parameters, histopathological examination

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Authors: Venencia Albert, Arulselvi Subramanian, Hara Prasad Pati, Asok K. Mukhophadhyay

Abstract:

Acute traumatic coagulopathy in an endogenous dysregulation of the intrinsic coagulation system in response to the injury, associated with three-fold risk of poor outcome, and is more amenable to corrective interventions, subsequent to early identification and management. Multiple definitions for stratification of the patients' risk for early acute coagulopathy have been proposed, with considerable variations in the defining criteria, including several trauma-scoring systems based on prehospital data. We aimed to develop a clinically relevant definition for acute coagulopathy of trauma based on conventional coagulation assays and to assess its efficacy in comparison to recently established prehospital prediction models. Methodology: Retrospective data of all trauma patients (n = 490) presented to our level I trauma center, in 2014, was extracted. Receiver operating characteristic curve analysis was done to establish cut-offs for conventional coagulation assays for identification of patients with acute traumatic coagulopathy was done. Prospectively data of (n = 100) adult trauma patients was collected and cohort was stratified by the established definition and classified as "coagulopathic" or "non-coagulopathic" and correlated with the Prediction of acute coagulopathy of trauma score and Trauma-Induced Coagulopathy Clinical Score for identifying trauma coagulopathy and subsequent risk for mortality. Results: Data of 490 trauma patients (average age 31.85±9.04; 86.7% males) was extracted. 53.3% had head injury, 26.6% had fractures, 7.5% had chest and abdominal injury. Acute traumatic coagulopathy was defined as international normalized ratio ≥ 1.19; prothrombin time ≥ 15.5 s; activated partial thromboplastin time ≥ 29 s. Of the 100 adult trauma patients (average age 36.5±14.2; 94% males), 63% had early coagulopathy based on our conventional coagulation assay definition. Overall prediction of acute coagulopathy of trauma score was 118.7±58.5 and trauma-induced coagulopathy clinical score was 3(0-8). Both the scores were higher in coagulopathic than non-coagulopathic patients (prediction of acute coagulopathy of trauma score 123.2±8.3 vs. 110.9±6.8, p-value = 0.31; trauma-induced coagulopathy clinical score 4(3-8) vs. 3(0-8), p-value = 0.89), but not statistically significant. Overall mortality was 41%. Mortality rate was significantly higher in coagulopathic than non-coagulopathic patients (75.5% vs. 54.2%, p-value = 0.04). High prediction of acute coagulopathy of trauma score also significantly associated with mortality (134.2±9.95 vs. 107.8±6.82, p-value = 0.02), whereas trauma-induced coagulopathy clinical score did not vary be survivors and non-survivors. Conclusion: Early coagulopathy was seen in 63% of trauma patients, which was significantly associated with mortality. Acute traumatic coagulopathy defined by conventional coagulation assays (international normalized ratio ≥ 1.19; prothrombin time ≥ 15.5 s; activated partial thromboplastin time ≥ 29 s) demonstrated good ability to identify coagulopathy and subsequent mortality, in comparison to the prehospital parameter-based scoring systems. Prediction of acute coagulopathy of trauma score may be more suited for predicting mortality rather than early coagulopathy. In emergency trauma situations, where immediate corrective measures need to be taken, complex multivariable scoring algorithms may cause delay, whereas coagulation parameters and conventional coagulation tests will give highly specific results.

Keywords: trauma, coagulopathy, prediction, model

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Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

Abstract:

Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

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Authors: Thieu-Thi Tra My

Abstract:

Undifferentiated embryonal sarcoma of the liver (UESL), a rare malignant mesenchymal tumor, is commonly seen in children. The symptoms and imaging were not specific, so it could be mimicked with other tumors or liver abscesses. The tumor often appears as a large heterogeneous echoic solid mass with small cystic areas while showing a cyst-like appearance on CT and MRI. The histopathological manifestation of the UESL consisted of stellate-shaped and spindle cells scattered on a myxoid background with high mitotic count. Cells with multiple or bizarre nuclear were also observed. Here, we aimed to describe a 9-year-old male diagnosed with UESL focused on imaging and histopathological characteristics.

Keywords: undifferentiated embryonal sarcoma of liver, UESL, liver sarcoma, liver tumor, children

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Authors: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

Abstract:

Coronary artery dissection leading to acute myocardial infarction after blunt chest trauma is extremely rare. A 67-year-old woman suffered blunt chest trauma following a traffic accident. The electrocardiogram revealed acute posterior ST-segment elevation and myocardial infarction and coronary angiography demonstrated acute right coronary artery dissection. Following the death of the victim an autopsy was performed after cardiopulmonary support had been carried out. In this case report, we describe the case of a woman with blunt chest trauma, who developed an acute myocardial infarction secondary to right coronary artery dissection. Although there was additional the blunt chest trauma due to chest compression, we confirmed the injury at autopsy and by histological findings.

Keywords: blunt chest trauma, right coronary artery dissection, coronary angiography, autopsy, histological examination

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Authors: Khenenou Tarek

Abstract:

Aim: The objective of present study was to compare the normal macro and microscopic appearance of the liver in two very different species, one is an omnivorous mammal; the wild boar and the other belongs to the family of poultry; broiler chicken from the region of Bouhmama (Khenchela). Materials and methods: Eight broilers (58 days of age) and eight wild boars were included in the experiment to obtain information about the morpho-histological appearances of liver in two species. Results: There is a big difference in the liver appearance between the two species, in the wild boar it is of firm consistency with a tiger aspect and divided into four lobes, whereas in the broiler, the liver is brown and sometimes pale during the first 10-14 days, so it was divided into two lobes. Concerning the liver parenchyma, we used the Russian LOMBO MBS-10 stereo microscope, our results showed that the liver parenchyma was well developed in wild boar than in broiler chickens whereas, in broiler chickens; an excessive development of the sinus; the latter were less developed in the wild boar. Conclusion: The macroscopic observation showed a marked difference in liver between the two species. The microscopic examination of liver showed that the parenchyma is less pronounced in broilers whereas the sinuses were highly developed in the wild boar.

Keywords: broiler chicken, liver, macro and microscopic appearances, wild boar, Algeria

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Authors: Maomao Cao

Abstract:

Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

Procedia PDF Downloads 150