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AST
Kinds of AST Terms modified by AST Selected AbstractsFunctional consistency across two behavioural modalities: fire-setting and self-harm in female special hospital patientsCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 1 2007Sarah Miller Background,Fire-setting and self-harm behaviours among women in high security special hospitals may be understood using Shye's Action System Theory (AST) in which four functional modes are recognized: ,adaptive', ,expressive', ,integrative', and ,conservative'. Aims,To test for relationships between different forms of fire-setting and self-harm behaviours and AST modes among women in special hospital, and for consistency within modes across the two behaviours. Method,Clinical case files evidencing both fire-setting and self-harm behaviours (n = 50) were analysed for content, focusing on incident characteristics. A total of 29 fire-setting and 22 self-harm variables were analysed using Smallest Space Analysis (SSA). Chi-square and Spearman's rho (,) analyses were used to determine functional consistency across behavioural modes. Results,Most women showed one predominant AST mode in fire-setting (n = 39) and self-harm (n = 35). Significant positive correlations were found between integrative and adaptive modes of functioning. The lack of correlation between conservative and expressive modes reflects the differing behaviours used in each activity. Despite this, significant cross-tabulations revealed that each woman had parallel fire-setting and self-harm styles. Discussion,Findings suggest that, for some women, setting fires and self harm fulfil a similar underlying function. Support is given to AST as a way of furthering understanding of damaging behaviours, whether self- or other-inflicted. Copyright © 2007 John Wiley & Sons, Ltd. [source] Mouse toxicity of Anabaena flos-aquae from Lake Dianchi, ChinaENVIRONMENTAL TOXICOLOGY, Issue 1 2009Xiaojie Pan Abstract Some species of the genera Anabaena can produce various kinds of cyanotoxins, which may pose risks to environment and human health. Anabaena has frequently been observed in eutrophic freshwater of China in recent years, but its toxicity has been reported only in a few studies. In the present study, the toxicity of an Anabaena flos-aquae strain isolated from Lake Dianchi was investigated. Acute toxicity testing was performed by mouse bioassay using crude extracts from the lyophilized cultures. The mice exposed to crude extracts showed visible symptoms of toxicity and died within 10,24 h of the injection. Serum biochemical parameters were evaluated by the use of commercial diagnostic kits. Significant alterations were found in the serum biochemical parameters: alkaline phosphatase (AKP), ,-glutamyl transpeptidase (,-GT), aspartate amino transferase (AST), alanine amino transferase (ALT), AST/ALT ratio, total protein content, albumin content, albumin/globulin (A/G) ratio, blood urea nitrogen (BUN), serum creatinine (Ssr), and total antioxidative capacity (T-AOC). Histopathological observations were carried out with hematoxylin and eosin (HE) stain under light microscope. Severe lesions were seen in the livers, kidneys, and lungs of the mice injected with crude extracts. The alterations of biochemical parameters were in a dose-dependent manner, and the severities of histological lesions were in the same manner. Based on biochemical and histological studies, this research firstly shows the presence of toxin-producing Anabaena species in Lake Dianchi and the toxic effects of its crude extracts on mammals. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in miceENVIRONMENTAL TOXICOLOGY, Issue 5 2007R. Jayaraj Abstract Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that represents acute and chronic hazards to animal and human health. Identification of suitable chemprotectants against microcystin is essential considering human health hazards. In the present study, we have evaluated the protective efficacy of three flavanoids namely quercetin (200 mg/kg), silybin (400 mg/kg), and morin (400 mg/kg)] pretreatment against microcystin toxicity (0.75 LD50, 57.5 ,g/kg) in mice. Various biochemical variables were measured to study the recovery profile of protected animals at 1- and 3-days post-toxin treatment. The serum alanine amino transferase (ALT) shows 17-fold increase in MC-LR treated animals compared with control group at 1 day. The silybin and quercetin group showed a decrease in level of ALT compared with MC-LR group but still higher than control group. No significant protection was observed with aspartate aminotransaminase (AST) and lactate dehydrogenase (LDH) levels in flavanoid-treated groups at 1-day post-treatment. But at 3 days, the serum levels of AST and ALT were normalized to control values, but the serum LDH levels were still significantly higher than the control group. No significant changes were observed in glutathione peroxidase and reduced glutathione levels at both 1- and 3-day postexposure. The catalase activity shows a significant decrease in quercetin-treated animals at 3-day postexposure. The protein phosphatase was significantly inhibited in MC-LR group compared to control. The silybin pretreated group showed recovery after 1 day. At 3 days, the PPAse activity was reversed to control values in all the flavanoid-treated groups. Immunoblotting analysis showed microcystin-PPAse adduct in liver tissues of toxin-treated as well as flavanoid-treated mice even after 3 days. The results of this study show that flavanoids, quercetin, silybin, and morin could reverse the hepatotoxic effects of MC-LR in vivo. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 472,479, 2007. [source] Valproic Acid-Induced Hyperammonemic Encephalopathy with Triphasic WavesEPILEPSIA, Issue 7 2000Akira Kifune Summary: Purpose: To examine a patient with valproic acid (VPA)-induced hyperammonemic encephalopathy accompanied by triphasic waves. Methods: A 61-year-old male patient with epilepsy experienced disturbance of consciousness after VPA dose was increased because of poor seizure control. The electroencephalogram (EEG) taken on admission revealed triphasic waves and high-amplitude ,-activity with frontal predominance. Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonium level was high at 96 ,g/dl (normal range, 3,47 ,g/dl). Serum amino acid analysis showed multiple minor abnormalities. Administration of VPA was discontinued immediately after admission, while other anticonvulsants were continued. Results: The patient's condition was improved on the fourth day of admission. An EEG, serum ammonium level, and amino acid profile were normal on the eighth day. Based on VPA administration, serum ammonium levels, and results of amino acid analysis, this patient had VPA-induced hyperammonemic encephalopathy. Conclusions: Our case indicates that caution is required if triphasic waves appear in VPA-induced hyperammonemic encephalopathy. [source] Bilateral degenerative suspensory desmitis with acute rupture in a Standardbred coltEQUINE VETERINARY EDUCATION, Issue 6 2010K. D. Miller Summary A 3-month-old Standardbred colt was examined for acute, bilateral hindlimb swelling and lameness. Serum chemistry demonstrated elevated muscle enzymes (AST, ALT, LDH and CK). Radiographs of the hindlimbs demonstrated intact proximal sesamoid bones that were displaced distally and subluxation of the pastern joints. Ultrasonography of the affected areas revealed large, diffuse hypoechoic areas in the bodies of both hind suspensory ligaments consistent with bilateral rupture. Histology of the lesions was consistent with degenerative suspensory desmitis with acute rupture. [source] Predicting the development of early skin test sensitization in offspring of parents with asthmaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2007Y. Jin Abstract Background, The direct causal relationship between skin sensitization and asthma are controversial until now and remains to be further researched. Our aim is to analyse the role of parental asthma in the development of skin sensitization in offspring. Materials and methods, This study was performed among nuclear families (determined by index of asthma patients), and subjects included parents and offspring. Parents were subdivided into four phenotypes on the basis of skin sensitization (SPT+ or SPT,) and asthma status (AST+ or AST,) and offspring were subdivided into three age groups: 3,8, 9,14 and 15,20 years. The main tests included a standard questionnaire and skin prick tests. Results, Offspring's skin sensitization differed among parental phenotypes at all ages (P < 0·05). In the SPT+/AST,, SPT,/AST+ and SPT+/AST+ groups, offspring were significantly more likely to be allergic than the ones in SPT,/AST, group at 3,8 years. Offspring with at least one parent with asthma were significantly more likely to have positive skin prick test response than those with non-asthmatic parents at age 3,8 years and 9,14 years, but not at 15,20 years among offspring with allergic parents. Results were independent of asthma in the children and of the characteristics of atopy in the parents. Conclusion, Parent asthma history is an independent risk factor for allergic sensitization in their offspring in a Chinese population. [source] HEPATITIS C AND ADDICTION: Chronic viral hepatitis is a significant contributor to the immunosenescent phenotype of parenteral drug addictionADDICTION BIOLOGY, Issue 2 2009Albert S. Reece ABSTRACT Intravenous drug addiction is known to be associated with an inordinate morbidity and mortality. As our previous report had identified an immune phenotype consistent with accelerated ageing, we wished to investigate how much of this change may have been related to chronic viral hepatitis. A total of 12 409 clinical pathology results from the period 1995,2007 were reviewed. To control for the differences in age, only patients less than 48 years of age were considered. A total of 636 substance use disorder (SUD) and 6103 non-SUD (N-SUD) patients were studied. They had comparable ages (mean ± SD 31.32 ± 6.90 versus 31.57 ± 9.23, P -value not significant), but the SUD group had more males (74.37% versus 53.20%, P < 0.001). For most of the changes examined splitting the two SUD groups into hepatitis C positive (HCV+) and hepatitis C negative (HCV,) demonstrated that the majority of the described changes were most marked in the HCV+ group. The globulins were higher in the HCV+ group and the albumin was lower and fell more markedly with age than in N-SUD or HCV, (all P < 0.001). The globulin/albumin ratio was significantly higher in HCV+ than HCV, or N-SUD (both P < 0.0001) and rose more with age. These changes were paralleled by the ESR, elevations in the CRP and lymphocyte count. Transaminases were elevated in SUD and HCV+ groups compared with N-SUD (all P < 0.02). At multivariate analysis ESR, lymphocyte count, dual hepatitis B and C seropositivity, AST and HCVAb were significant predictors of the serum globulin level and accounted for 21% of the variance. These data extend our earlier report and show that much of the immunosenescent phenotype of SUD, encompassing the known immunosuppression and the observed immunostimulation, is statistically related to chronic viral hepatitis. Important theoretical and practical management (vaccination) implications ensue. [source] Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2005M.A.R.C.P. Silva Abstract The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats. [source] Experimental study on a new type citrate anticoagulant hemodialysate in dogsHEMODIALYSIS INTERNATIONAL, Issue 1 2005G. Baosong Objective:,In this study, we initiated a new hemodialysate with citrate buffer, observed the factors that influence the citrate concentration of solution in hollow fibers when using citrate hemodialysate, and observed the anticoagulant effect and safety of the citrate hemodialysate in the experiment in dogs. Methods:,Ten dogs were given intermittent hemodialysis and were divided into 3 groups according to hemodialysis procedures. Group 1 was saline-flush hemodialysed with bicarbonate hemodialysate; Group 2 was hemodialysed with citrate hemodialysis without any anticoagulant; Group 3 was hemodialysed with bicarbonate hemodialysate and heparin. ACT, Ca++, BUN, Cr, ALT, AST, TBIL, DBIL, Na+, Cl,, , and venous pressure were monitored in the animals of each group during hemodialysis. Results:,During the hemodialysis in Group 1, venous pressure increased lastingly, resulting in the failure of hemodialysis for 2 hours. Hemodialysis for 2 hours in Group 2 were all finished successfully. ACT was extended and Ca++ decreased obviously in the venous end during hemodialysis. And ALT, AST, Ca++, K+, Na+, Cl,, after the hemodialysis in Group 2 were not changed (P > 0.05). Moreover, the clearance rate of the dialyzers with citrate dialysate increased significantly compared with those of saline-flush and heparin anticoagulation. Conclusions:,The anticoagulant and dialytic effects of the new type citrate hemodialysis are satisfactory and better than that of saline-flush. [source] Serum aminotransferase activity and mortality risk in a United States community,HEPATOLOGY, Issue 3 2008Tae Hoon Lee Serum aminotransferase [such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] is commonly used as an indicator of liver disease. The aim of the study was to determine the degree to which aminotransferase results are associated with increased mortality at the population level. All adult residents of Olmsted County, Minnesota, who had a health care encounter at Mayo Clinic, Rochester, in 1995 were identified and their AST or ALT results extracted from a laboratory database. These subjects were followed forward from January 1995 to April 2006 and their survival determined. To exclude patients with abnormal results because of a terminal illness, deaths within the first 2 years were excluded. The main outcome measure was survival. Standardized mortality ratios (SMRs) were calculated, based on Minnesota White death rates. During 1995, AST was measured at least once in 18,401 community residents, of whom 2,350 (13%) had results greater than the upper limit of normal (ULN). Of 6,823 subjects who had their ALT measured, 911 (13%) had results higher than ULN. Abnormal AST was associated with a significantly increased SMR (1.32 for 1,2× ULN and 1.78 for >2× ULN). SMR was also higher for abnormal ALT (SMR = 1.21 for 1,2× ULN and 1.51 for >2× ULN). In contrast, normal AST or ALT was associated with a risk of death lower than expected (SMR 0.95 for AST, 0.61 for ALT). Conclusion: Serum levels of AST and ALT obtained in a routine medical care setting are associated with future mortality in community residents. (HEPATOLOGY 2008;47:880,887.) [source] Enhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: Role of cytochrome P450 2E1 and 2A5,HEPATOLOGY, Issue 1 2006Yongke Lu The mechanisms by which alcohol causes liver injury are still not certain. Either LPS or CYP2E1 are considered independent risk factors involved in alcoholic liver disease, but mutual relationships or interactions between them are unknown. In the present study, the possible synergistic action of CYP2E1 and LPS in liver injury was investigated by evaluating the effects of pyrazole (inducer of CYP2E1), Chlormethiazole (CMZ), an inhibitor of CYP2E1, and CYP2E1-knockout mice. Mice were injected with pyrazole (150 mg/kg, ip) daily for 2 days, followed by LPS injection (4 mg/kg, ip). CMZ (50mg/kg, ip) was administered 15 h before and 30 min after LPS treatment, respectively. LPS-induced liver injury was enhanced by pyrazole, as indicated by pathological changes and increases in ALT and AST, and positive TUNEL staining. LPS-induced oxidative stress was also enhanced by pyrazole as indicated by increases in 4-hydroxy-2-nonenal and 3-nitrotyrosine adduct formation. CMZ protected against the pyrazole enhanced LPS liver injury and oxidative stress. CYP2E1 but also CYP2A5 were increased by the pyrazole/LPS treatment. CMZ decreased the elevated CYP2E1 activity by 90%, but CYP2A5 activity was also lowered (30%-50%). CYP2E1-knockout mice exhibited only minor liver injury after treatment with pyrazole/LPS, but wild-type mice exhibited severe liver injury. While no CYP2E1 was present in the CYP2E1 knockout mice, CYP2A5 activity was also lower. In conclusion, induction of CYP2E1 plays an important role in the enhancement of LPS liver injury by pyrazole, but some contribution by CYP2A5 cannot be excluded. (HEPATOLOGY 2006;44:263,274.) [source] Adiponectin protects LPS-induced liver injury through modulation of TNF-, in KK-Ay obese miceHEPATOLOGY, Issue 1 2004Takayuki Masaki Adiponectin, an adipocytokine, has been identified in adipose tissue, and its receptors are widely distributed in many tissues, including the liver. The present study was performed to clarify the role of adiponectin in lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed the effects of adiponectin pretreatment on liver injury induced by D -galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver injury was more pronounced in KK-Ay obese mice than in lean controls. Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum AST and ALT levels and the apoptotic and necrotic changes in hepatocytes, resulting in a reduction in lethality. In addition, pretreatment with adiponectin attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis factor , (TNF-,) levels and increased peroxisome proliferator-activated receptor (PPAR) , messenger RNA expression in the liver. Furthermore, abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro exhibited decreased LPS-induced TNF-, production compared with controls. Finally, adiponectin pretreatment also ameliorated TNF-,-induced liver injury. In conclusion, these findings suggest that adiponectin prevents LPS-induced hepatic injury by inhibiting the synthesis and/or release of TNF-, of KK-Ay obese mice. (HEPATOLOGY 2004;40:177,184.) [source] A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis CHEPATOLOGY, Issue 2 2003Chun-Tao Wai Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score , 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients. [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Histologic and biochemical changes during the evolution of chronic rejection of liver allograftsHEPATOLOGY, Issue 3 2002Desley A. H. Neil Criteria for histologic diagnosis of chronic rejection (CR) are based on changes seen late in the disease process that are likely to be irreversible and unresponsive to treatment. Changes occurring during the evolution of CR are less clearly defined. The serial biopsy specimens, failed allografts, and biochemical profiles of 28 patients who underwent retransplantation for CR were examined with the aim of identifying histologic and biochemical features that were present during the early stages of CR. For each case, a point of acute deterioration in liver function tests (LFTs) was identified ("start time" [ST]) that subsequently progressed to graft failure. Biopsy specimens before, at the time of ("start biopsy" [SB]), and after the ST were assessed histologically, and findings were correlated with the biochemical changes. CR resulted from acute rejection (AR) that did not resolve. Centrilobular necroinflammation (CLNI) associated with an elevated aspartate transaminase (AST) level and portal tract features of AR were present at the start. Portal AR features resolved, CLNI persisted, AST level remained elevated, and bilirubin and alkaline phosphatase levels progressively increased throughout the evolution of CR. Portal tracts also showed a loss of small arterial and bile duct branches, with arterial loss occurring early and bile duct loss as a later progressive lesion. Foam cell arteriopathy was rarely seen in needle biopsy specimens. In conclusion, findings from this study may help identify patients at risk of progressing to graft loss from CR at a stage when the disease process is potentially reversible and amenable to treatment. [source] Cholestasis enhances liver ischemia/reperfusion-induced coagulation activation in ratsHEPATOLOGY RESEARCH, Issue 2 2010Jaap J. Kloek Aim:, Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods:, Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results:, Plasma AST and ALT levels were higher after I/R in cholestatic rats (P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion (P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion (P < 0.05). I/R in cholestatic rats resulted in a 12-fold vs. 7-fold (P < 0.01) increase in markers for thrombin generation and a 6-fold vs. 2-fold (P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1) during reperfusion. Conclusions:, Cholestasis significantly enhances I/R-induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis. [source] Selective CB1 cannabinoid receptor antagonist, SR141716A, attenuates liver injury induced by Concanavalin AHEPATOLOGY RESEARCH, Issue 4 2009Midori Kojima Aim:, The aim of this study was to investigate the hepatoprotective activity of a selective cannabinoid receptor 1 (CB1) antagonist, SR141716A, in a Concanavalin A (Con A)-induced mouse liver injury model and to determine whether SR141716A has an effect on the production of inflammatory cytokines and chemokines induced by Con A. Results:, Injection of Con A (20 mg/kg) to mice developed hepatitis determined by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation and necrosis in the liver. Pretreatment with SR141716A (30 mg/kg) significantly reduced plasma AST and ALT level, protected against necrosis in the liver, and significantly reduced plasma cytokine and chemokine levels, including TNF,, IFN-,, CXCL9, MIP1-,, and IL-10 and no change decreased in IL-4. Conclusions:, The selective CB1 antagonist, SR141716A, exerts a hepatoprotective effect on Con A-induced liver injury in mice by attenuating the increase in cytokine and chemokine levels and inhibiting hepatocyte injury. These findings raise the possibility of using CB1 antagonists as anti-inflammatory drugs for treating hepatitis as well as other inflammatory diseases. [source] Protective effect of non-mitogenic human acidic fibroblast growth factor on hepatocyte injuryHEPATOLOGY RESEARCH, Issue 10 2007Hua Xu Aim:, To study whether non-mitogenic human acidic fibroblast growth factor (nm-haFGF) has protective effects on H2O2 -induced hepatocyte injury in vitro and CCl4 -induced hepatocyte injury in vivo. Methods:, (i) HL-7702 hepatocytes were incubated with different concentrations of nm-haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H2O2 (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl-2 and Bax of HL-7702 cell were detected after being exposed to H2O2 (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm-haFGF, mice were treated with CCl4 intraperitoneally to induce hepatic injury. Twenty-four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated. Results:, (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl-2 increased and Baxdecreased in nm-haFGF-treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H2O2 alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm-haFGF-treated groups (10 ,g/kg and 20 ,g/kg) were much lower as compared to the model control group, which was treated with CCl4 alone. Histological examination showed that nm-haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl4. Conclusion:, nm-haFGF had protective effects against H2O2 -induced hepatocyte injury in vitro and CCl4 -induced acute liver injury in vivo. [source] Hepatitis C virus infection among HIV-1 infected individuals from northern MexicoHEPATOLOGY RESEARCH, Issue 5 2007Ana M. Rivas-Estilla Aims:, The prevalence of hepatitis C virus (HCV) infection, risk factors and HCV genotypes in 140 HIV-1 infected individuals from northern Mexico was determined. Methods:, Hepatitis C infection was confirmed by the detection of anti-HCV antibodies and HCV-RNA in sera, and genotyping was performed by the InnoLiPA-HCV genotype assay. Results:, Seventeen (12.1%) out of 140 HIV-infected individuals were found to be HCV-positive. Coinfected individuals were more likely to be male (87%). The most frequent genotype was 1a (41%), followed by 1b (29.4%), 2a/c (17.6%), 2b (5.9%) and 3 (5.9%). Serum transaminase concentrations (AST and ALT) were higher in coinfected patients. Among the risk factors for coinfection: sexual transmission was the most frequently observed (men who have sex with men (MSM); 64.7% and bisexual behavior; 64.7%) followed by intravenous drug users (IVDU) (53%). There was no association of the HCV genotypes with the age and risk factors for HIV-1 and HCV infection observed in the studied patients. Conclusion:, The results suggest that the prevalence of HIV-1/HCV coinfection in Mexico is lower than in other American countries. [source] Validation of a simple model for predicting liver fibrosis in HIV/hepatitis C virus-coinfected patientsHIV MEDICINE, Issue 6 2005H Al-Mohri Objectives Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono-infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection. Methods Forty-six HIV/HCV-coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (±3 months) were included in the study. Significant fibrosis was defined as F2,F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (109/L)] × 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut-offs previously identified in the literature. Results Thirty-three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847±0.057. APRI scores >1.5 (the higher cut-off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut-off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%). Conclusions A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy-sparing measure, thus making treatment more accessible for this population. [source] Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia,reperfusion injury and clinical relevanceHPB, Issue 7 2010Paola Andreani Abstract Background:, Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). Objective:, To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. Patients and methods:, Alternate patients were transplanted with right lobe grafts that were (n= 22; Group Precond) or were not (n= 22; Group Control) subjected to IPC in the living donor. Liver ischaemia,reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. Results:, Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P= 0.8) and alanine aminotransferase (ALT) peaks (P= 0.6) were similar in both groups (307 ± 189 and 437 ± 302 vs. 290 ± 146 and 496 ± 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P= 0.003) and pre-operative bilirubin concentration (P= 0.004) were significantly predictive of minimum prothrombin time post-transplantation. Conclusions:, Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain. [source] Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remissionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Tomonobu Ito MD A 76-year-old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (67Ga single-photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T-cell lymphoma, nasal. Because imaging analysis indicated a small-sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low-dose steroid therapy. ,Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen (Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 106/µL), and platelet count (112 × 103/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224,454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10,30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3,29 U/L) levels were elevated. The soluble interleukin-2 (IL-2) receptor level was high (25,300 U/mL; normal, 167,497 U/mL). Epstein,Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen-diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes (Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3,, CD4,, CD8,, CD20,, CD56+, granzyme B+, and T-cell intracellular antigen (TIA-1) positive. Furthermore, EBV-encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T-cell receptor-, (TCR-,), TCR-,, and TCR-, gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T-cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m2, cyclophosphamide 500 mg/m2, vincristine 1 mg/m2, prednisolone 30 mg/m2, etoposide 80 mg/m2). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. Figure 1. Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen Figure 2. Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400) [source] Erythema dyschromicum perstans and hepatitis C virus infectionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2001George J. Kontochristopoulos MD A 48-year-old woman with a 10-month history of widespread, hyperpigmented, slightly pruritic macules, with a red border, involving the trunk and the proximal limbs (Fig. 1) was referred to our outpatient department. The oral mucosa, palms, soles, scalp, and nails were normal. Figure 1. Multiple hyperpigmented macules with an active border on the trunk Laboratory tests showed elevated liver enzymes [alanine aminotransferase (ALT), 68 IU/L (normal value, <,40 IU/L); aspartate aminotransferase (AST), 41 IU/L (normal value, <,40 IU/L)], the presence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA (Amplicor Roche). In addition, cryoglobulinemia type III (IgM,,,, IgG,,,) was detected with a high cryocrit value, and there was detectable C-reactive protein, rheumatoid factor, and a low titer of antinuclear antibodies (1 : 80). A percutaneous liver biopsy showed changes compatible with mild chronic hepatitis (grade, 6; stage, 0). The possible source of infection was unknown, as the patient had no history of parenteral transmission (e.g. blood transfusions, intravenous illicit drug use). A skin biopsy specimen from the active border of a lesion showed hyperkeratosis, parakeratosis, and hydropic degeneration of the basal cell layer, with the formation of colloid bodies in the epidermis. A moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules was observed in the upper dermis (Fig. 2). Immunostaining of paraffin-embedded tissue sections with the TORDJT-22 IgG1 mouse monoclonal antibody to HCV (Biogenex, Son Ramon, USA), which is specific for the nonstructural region of HCV (NS3-NSH, C100 antigen) using the avidin,biotin,peroxidase complex (ABC) as well as the alkaline phosphatase antialkaline phosphatase (APAAP) methods, failed to detect HCV in the lesion of erythema dyschromicum perstans (EDP) (Nakopoulou L, Manolaki N, Lazaris A et al. Tissue immunodetection of C100 hepatitis C virus antigen in major thalassemic patients. Hepato-Gastroenterol 1999; 46: 2515,2520). Direct immunofluorescence showed IgG, IgM, IgA, and fibrinogen deposits on colloid bodies. EDP was diagnosed on the basis of these clinical and laboratory findings. Figure 2. Hydropic degeneration of the basal cell layer with colloid bodies in the epidermis. Moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules in the upper dermis (hematoxylin and eosin, ×,200) The patient was treated with interferon-,2b (Intron-A, Schering Plough Athens, Greece), 3 MU thrice weekly subcutaneously for 12 months, with additional topical steroid application. There was no response to this treatment with new lesions appearing in previously unaffected areas of the trunk and extremities. HCV RNA remained persistently positive. Thus, a modified regimen with interferon-,2b, 6 MU thrice weekly for 6 months, was tried. At the end of the treatment course, the eruption of EDP had greatly improved. Liver enzymes were normal (ALT, 22 IU/L; AST, 24 IU/L) and HCV RNA had become negative. Four months later, however, cutaneous lesions reappeared and hepatitis C relapsed. At this time point, combination therapy of interferon-,2b, 3 MU thrice weekly, with ribavirin, 1000 mg daily, was given. Six months later, liver enzymes were normal (ALT, 42 IU/L; AST, 39 IU/L), HCV RNA was negative, and the lesions of EDP had resolved. [source] Dermatomyositis presenting as panniculitisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2000Yen-Yu Chao MD A 44-year-old obese woman was transferred to our clinic with a diagnosis of panniculitis. Examination showed multiple, indurated, erythematous, painful nodules and plaques distributed on the shoulders, back, forechest, abdomen, buttock, and bilateral thighs. These skin lesions appeared 2 months previously, measured 5,8 cm, and were tender on palpation. No obvious inducing factor was traced. The lesions seemed unresponsive to treatment with nonsteroidal anti-inflammatory drugs (ibuprofen, 400 mg three times a day) as similar lesions appeared in subsequent visits. Progressive proximal muscle weakness was found 1 month later. She was then admitted via the emergency room because of extensive painful skin plaques and abdominal pain. Diffuse erythematous to violaceous swelling of the face, neck, and shoulder was noted at about the same time ( Fig. 1). A skin biopsy specimen from the nodular lesion showed poikilomatous epidermal changes ( Fig. 2), and marked mononuclear cell infiltration in the dermis and subcutaneous fat ( Fig. 3). Dermatomyositis was considered as the diffuse violaceous facial erythema could be a form of heliotrope eruption, but Gottron's papule was not found. At admission, serum creatinine phosphokinase (CPK) was mildly elevated (436 IU/L; normal range, 20,170 IU/L), but serum asparagine transaminase (AST) and lactate dehydrogenase (LDH) levels were within normal limits (36 IU/L; normal, 11,47 IU/L; and 108 IU/L; normal, 90,280 IU/L, respectively). Antinuclear antibody was 1 : 80 positive with an atypical speckled pattern. Muscle strength was weakest during the first 2 days, about grade 3 by the Medical Research Council (MRC) of Great Britain scale. Gower's sign was positive. An electromyogram showed myopathic changes and a nerve conduction velocity study was normal. Serum enzymes were elevated further on the third day: AST, 55 IU/L; CPK, 783 IU/L with 100% MM form. The diagnosis of dermatomyositis was established. As for the work-up result, anti-dsDNA antibody, anti-ENA antibody, and anti-Jo1 antibody were negative. Tumor marker screen (,-HCG, AFP, CEA, and CA-125), was negative, and rhinolaryngopharyngoscope examination and gynecologic sonography were normal. Figure 1. Diffuse erythematous swelling with subtle violaceous hue extending from the temporal area to the cheeks, neck, and shoulders. The crusted lip ulcers of herpes simplex were also noted Figure 2. Basketweave hyperkeratosis, mild acanthosis, subtle vacuolar degeneration of the basal cells, and melanin incontinence (hematoxylin and eosin, ×400) Figure 3. Heavy mononuclear cells infiltrated in the subcutaneous fat tissue (hematoxylin and eosin, ×100) Pancreatitis was initially suspected because of epigastric pain and tenderness, elevated serum lipase (382 U/L; normal, 23,200 U/L), and amylase (145 U/L; normal, 35,118 U/L). No evidence of pancreatitis could be found in abdominal sonography and abdominal computed tomography (CT), however. The epigastric pain and tenderness subsided soon after admission and the serum pancreatic enzyme level declined on the second day (amylase 69 U/L; lipase, 276 U/L). The patient was then diagnosed with dermatomyositis and treated with prednisolone (120 mg/day). CPK dropped dramatically from 3286 IU/L the day before treatment to 1197 IU/L 3 days after. Panniculitis lessened and the muscle power improved after 1 week of treatment. The disease activity fluctuated even with treatment with prednisolone and the patient often felt listless and weak. The muscle weakness sometimes deteriorated to affect the patient's mobility. Facial erythema and panniculitis-like lesions were found during the worse times. Methotrexate and azathioprine were then added (7.5 mg and 250 mg per week, respectively), but CPK was still mildly elevated (189 IU/L), and the patient still felt ill. Human immune globulin (5%, 500 mL per day, 5 days per month) intravenous infusion was initiated thereafter. There was a dramatic response. Full muscle strength was retained and CPK was within the normal range in the following 6 months with only immune globulin therapy. [source] Acute liver damage in anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 1 2004Lorenza Di Pascoli Abstract We report a case of a 26-year-old White woman with a history of anorexia nervosa who developed severe liver damage and multiorgan dysfunction. At admission to our medical unit, her body mass index (BMI) was 10.8. Biochemical evaluation showed a marked increase in serum levels of aspartate aminotransferases (AST = 9,980 IU/L), alanine aminotransferase (ALT = 3,930 IU/L), amylase (1,002 IU/L), lipase (1,437 IU/L), creatine phosphokinase (CPK; 783 IU/L), and lactate dehydrogenase (LDH = 6,830 IU/L). Glomerular filtration rate was reduced (35 ml/min), reflecting dehydration and prerenal azotemia. No other cause of acute liver damage except malnutrition was evidenced. Hydration and nutritional support were the unique medical treatment. A rapid recovery occurred in few days and all laboratory data were normal at discharge after a 37-day hospitalization. © 2004 by Wiley Periodicals, Inc. Int J Eat Disord 36: 114,117, 2004. [source] Effects of high-level dietary B-vitamins on performance, body composition and tissue vitamin contents of growing/finishing pigsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2007B. M. Böhmer Summary Forty-eight growing pigs were randomly assigned to five dietary groups and penned individually. They received a diet based on barley, wheat, corn and soya bean meal according to requirement. The experimental groups were supplemented with 400% or 800% of vitamins B2, B6 and pantothenic acid, or 400% or 800% of biotin, while all other vitamins were administered according to requirement. Growth performance, carcass characteristics, aspartate aminotransferase (AST), and content of vitamins in blood, liver and muscles were recorded. Growth performance showed no influence of supplementation, while backfat thickness in the group with 800% B2/B6/pantothenic acid was significantly higher. Content of B2 in blood, liver and muscle was similar in all groups. Content of B6 in blood and liver showed significant differences according to supplementation. The content of vitamin B6 in muscle in the experimental groups was significantly higher than that in the control group. The content of pantothenic acid in blood and muscle in the experimental groups was significantly higher, while in liver all groups were significantly influenced by the supplementation level. Biotin content in liver showed no influence, but the content in plasma was significantly higher in the experimental groups and the content in muscle was significantly higher according to supplementation. The activity of AST showed no significant influence of the dietary vitamin level, but it was obviously decreased in the groups supplemented with biotin. The findings indicate that the dietary supplementation of vitamin B2, B6, pantothenic acid and biotin could not improve performance, but the contents in blood, liver and muscle. [source] Evolution of blood parameters during weight loss in experimental obese Beagle dogsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2004M. Diez Summary The effects of weight loss on hormonal and biochemical blood parameters were measured monthly [carnitine, creatinine, urea, free T4 (fT4), total T4 (TT4), plasma alkaline phosphatases (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), potassium and total proteins] or bimonthly [cholesterol, triglycerides, non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I), glucose, insulin] in eight obese Beagles dogs fed either a high protein dry diet, DP (crude protein 47.5%, on dry matter basis) or a commercial high fibre diet, HF (crude protein 23.8%, crude fibre 23.3%). The dogs were allotted to two groups according to sex and body weight (BW) and they were respectively fed with the DP or the control HF diet during 12,26 weeks, until they reach their optimal BW. The plasma basal triglycerides and cholesterol concentrations were decreased by the two diets but the difference was only significant for the DP diet. The plasma mean NEFA concentration increased regularly over the period with the HF diet, without significant difference between the two diets. No effect of diet or weight loss was observed on plasma carnitine, urea, creatinine, ALP, AST, ALT, potassium, TT4, FT4, IGF-I, glucose and insulin. Weight loss induced a decrease in fT4 plasma concentration (p < 0.001). The high protein diet allowed a safe weight loss. [source] Efficacy of Beauveria bassiana (Bals.) Vuill. against the tarnished plant bug, Lygus lineolaris L., in strawberriesJOURNAL OF APPLIED ENTOMOLOGY, Issue 2 2008R. Sabbahi Abstract Beauveria bassiana has a high insecticidal potential to control the tarnished plant bug, Lygus lineolaris, a significant pest of strawberries. Screening experiments showed that L. lineolaris adults were susceptible to several B. bassiana isolates. Another screening test with Coleomegilla maculata, a natural enemy found in strawberries, was also performed in order to select the isolate having lower entomopathogenic impact on this insect. Based on data obtained from both insect species and on the ecozone origin of the B. bassiana isolates, INRS-IP and INRS-CFL isolates were selected for further experiments. The LC50 values of these two isolates against L. lineolaris adults were 7.8 × 105 and 5.3 × 105 conidia/ml, and average survival time (AST) values were 4.46 and 4.37 days at a concentration of 1 × 108 conidia/ml respectively. Results also indicated that L. lineolaris nymphs are susceptible to the selected isolates. During field experiments, using a randomized block design with four replicates, INRS-IP and INRS-CFL isolates were applied at two rates (1 × 1011 and 1 × 1013 conidia/ha) weekly during a period of 4 weeks. These multiple applications triggered a significant reduction of L. lineolaris nymphal populations in strawberries. Twenty-four days after the first application, a significant difference was observed between the mean population densities of surviving nymphs in all B. bassiana -treated plots (less than one insect per five plants) compared with those in control plots (four insects per five plants). During the field experiment, persistence of insecticidal activity and viability of B. bassiana conidia were also monitored. The results showed the presence of viable and infective conidia up to 6 days after each application on strawberry foliage. Moreover, the multiple applications of B. bassiana at the rate of 1 × 1013 conidia/ha triggered a significant reduction in strawberry fruit injuries induced by L. lineolaris feeding behaviour compared with the control plots. [source] Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2009Cristina W. Nogueira Abstract Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4 -induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (, -ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4. Copyright © 2008 John Wiley & Sons, Ltd. [source] Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respirationJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2008Cheuk-Sing Choy Abstract Sanguinarine (SANG) has been suggested to be one of the principle constituents responsible for the toxicity of Argemone mexicana seed oil. In this study, we focused on the possible mechanism of SANG-induced hepatotoxicity. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, hepatic vacuolization, lipid accumulation and lipid peroxidation of the liver were increased, and triglyceride (TG) was decreased in SANG-treated mice (10 mg kg,1 i.p.), indicating damage to the liver. SANG induced cell death and DNA fragmentation, in a concentration- (0,30 µm) and time-dependent (0,24 h) manner, and the cytotoxicity of SANG (15 µm) was accompanied by an increase in reactive oxygen species and a lessening in protein thiol content; these outcomes were reversed by glutathione, N -acetyl- l -cysteine and 1,4-dithiothretol, and slightly improved by other antioxidants in hepatocytes. SANG can affect the function of mitochondria, leading to the depletion of the mitochondrial membrane potential and adenosine 5,-triphosphate content of hepatocytes. SANG caused an uncoupling effect of the respiratory chain at lower concentrations, but inhibited the respiratory chain at higher concentrations in mitochondria isolated from rat liver. In conclusion, the data suggest that SANG is a liver toxin that induces cytotoxicity in liver cells, possibly through oxidation of protein thiols, resulting in oxidative stress on the cells and disturbance of mitochondrial function. 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