Hydrogen-rich water protects against acetaminopheninduced hepatotoxicity in mice

AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water(HRW) in acetaminophen(APAP)-induced liver injury in mice.METHODS: Male mice were randomly divided into the following four groups: normal saline(NS) control group, mice received equivalent volumes of NS intraperitoneally(ip); HRW control group, mice were given HRW(same volume as the NS group); APAP + NS group, mice received NS ip for 3 d(5 mL /kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d(same as NS treatment) after APAP challenge.In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates.In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg.Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.RESULTS :Treatment with HRW resulted ina significant increase in the 5-d survival rate compared with the APAP + NS treatment group(60% vs 26.67%, P 0.05).HRW could significantly decrease the serum alanine aminotransferase level(24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P 0.01; and3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P 0.05, respectively) and aspartate aminotransferase level(24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group.The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result.Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels.The liver index(5.16% ± 0.26% vs 5.88% ± 0.073%, P 0.05) and percentage of liver necrosis area(27.73% ± 0.58% vs 36.87% ± 0.49%, P 0.01) were significantly lower in the HRW-treated animals.The malonyldialdehyde(MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group(10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P 0.05).A decrease in superoxide dismutase(SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected(9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P 0.05).Furthermore, HRW could significantly increase the glutathione(GSH) contents(878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group.Meanwhile, HRW could reduce the inflammation level(serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P 0.01, respectively).In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502 E expression.Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.     

PI3K expression and PIK3CA mutations are related to colorectal cancer metastases

AIM: To assess the significance of phosphatidylinositol 3-kinase (PI3K) in colorectal cancer (CRC) and toxicity of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 in CRC cells with different metastatic abilities.METHODS: Sixty formalin-fixed and paraffin-embedded CRC tumor specimens were investigated. Adjacent normal colonic mucosa specimens from 10 of these cases were selected as controls. PI3K protein was detected by immunohistochemistry and PIK3CA mutations were investigated by gene sequencing analysis. A flow-cytometry-based apoptosis detection kit was used to determine PI3K inhibitor-induced apoptosis in CRC cell lines SW480 and SW620. Expression of phosphorylated protein kinase B in CRC cell lines was detected by Western blotting.RESULTS: There was a significant difference in the proportion of primary lesions (30%, 18/60) vs metastatic lesions (46.7%, 28/60) that were positive for PI3K (P < 0.05). Mutations were detected in exon 9 (13.3%) and exon 20 (8.3%). Out of 60 cases, seven mutations were identified: two hotspot mutations, C.1633G>A resulting in E545A, and C.3140A>G resulting in H1047R; two novel missense mutations C.1624G>A and C.3079G>A; and three synonymous mutations (C.1641G>A, C.1581C>T and C.3027T>A). Exposure of SW480 cells to PI3K inhibitor for 48 h resulted in a significant increase of apoptotic cells in a dose-dependent manner [3.2% apoptotic cells in 0 μmol/L, 4.3% in 5 μmol/L, 6.3% in 10 μmol/L (P < 0.05), and 6.7% in 20 μmol/L (P < 0.05)]. Moreover, PI3K inhibitor induced a similar significant increase of apoptotic cells in the SW620 cell line for 48 h [3.3% apoptotic cells in 0 μmol/L, 13.3% in 5 μmol/L (P < 0.01), 19.2% in 10 μmol/L (P < 0.01), and 21.3% in 20 μmol/L (P < 0.01)].CONCLUSION: High PI3K expression is associated with CRC metastasis. PI3K inhibitor induced apoptosis in CRC cells and displayed strong cytotoxicity for highly metastatic cells. PI3K inhibition may be an effective treatment for CRC.     

Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

AIM:To investigate the possible mechanisms of exogenous carbon monoxide-releasing moleculeⅡ(CORM-2)intervention on hepatic energy metabolism in experimental sepsis.METHODS:Forty-eight C57BL/6 mice were randomly divided into four groups(n=12):sham group;cecal ligation and puncture(CLP)group;CLP+CORM-2group and CLP+iCORM-2(inactive CORM-2)group.Survival rates were determined after 72 h.Twenty-four similarly treated mice(n=6 in each group)were assayed for post-operative continuous blood glucose in the first 36 h.Thirty-six similarly treated mice(n=9in each group)underwent micro-positron emission tomography(PET)scanning after tail vein injection of18Ffluorodeoxyglucose(FDG)24 h after operation.Plasma and liver specimens were collected for assay of liver pathology,alanine transaminase(ALT)and aspartate transaminase(AST)activities.Hepatic glucokinase activity,lactic acid levels and mitochondrial swelling were also determined.RESULTS:Improved survival was observed in CORM-2treated mice.Both the CLP and CLP+CORM-2 groups had sustained low blood glucose levels within the first post-operative 36 h.18F-FDG micro-PET images showed abnormally high levels of hepatic glucose metabolism(standardized uptake value)in the CLP group(2.76±0.39 vs 0.84±0.14,P<0.01),which declined to normal levels after CORM-2 intervention(1.29±0.32 vs2.76±0.39,P<0.05).glucokinase activity was markedly increased in the CLP group(6.38±0.56 U/g vs 4.60±0.21 U/g,P<0.01),but was normal after CORM-2intervention(4.74±0.14 U/g vs 6.38±0.56 U/g,P<0.05).CORM-2 suppressed plasma lactic acid levels(4.02±0.02 mmol/L vs 7.72±2.37 mmol/L,P<0.05)and protected hepatic mitochondria in CLP mice.CORM-2 intervention also reduced elevated plasma AST(199.67±11.08 U/L vs 379.67±16.34 U/L,P<0.05)and ALT(63.67±12.23 U/L vs 112.67±9.74 U/L,P<0.05)activities in CLP mice.CONCLUSION:The release of CO molecules by CORM-2 protects mitochondria and maintains a stable level of hepatic glucose metabolism.Thus,CORM-2 improves liver function and survival in septic mice.     

Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats

AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS ＋ Lianshu group, LPS ＋ berberine group （n = 10 in each group）. Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^＋, K^＋, Cl and hematocrit, plasma nitrogen monoxide （NO）, diamine oxidase （DAO）, and D （-）-lactate were measured. The number of IgA＋ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer＇s yeast-induced pyrexia （10 mL/kg of 20% aqueous suspension）. Acetaminophen （250 mg/kg, intragastric administration, bid） was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer＇s yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin （2 mg/kg）. Atropine （10 g/kg） was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS： The frequency of diarrhea was higher in LPS group than in LPS ＋ Lianshu group and LPS ＋ berberine group （36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01）, and lower in LP5 ＋ Lianshu group than in LPS ＋ berberine group （P = 0.03）. The levels of Na＋, glucose, Cl, K^＋ were significantly lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05）. The level of hematocrit was lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05）. The plasma levels of NO, DAO and D （-）-lactate were higher in LPS group than in normal group （79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01）, and lower in LPS ＋ Lianshu group than in LP5 ＋ berberine group （48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05）. The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS ＋ Lianshu group than in LPS group. The number of IgA＋ plasma cells and amount of SIgA were higher in LPS ＋ Lianshu group than in LPS group （1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000）. Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION： Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.     

Eradication of Helicobacter pylori increases childhood growth and serum acylated ghrelin levels

AIM: To determine whether Helicobacter pylori (H. pylori)-infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin.METHODS: This longitudinal cohort study with one-year follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after one-year follow-up were compared between successful eradicated H. pylori-infected children and controls.RESULTS: In the observation cohort, the H. pylori-infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori-infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori-infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up.CONCLUSION: H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.     

Impact of intestinal ischemia/reperfusion and lymph drainage on distant organs in rats

AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.     

High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated diverticular disease

AIM:To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms.METHODS:This study was a multicentre,6-mo randomized,controlled,parallel-group intervention with a preceding 4-wk washout period.Consecutive outpatients with symptomatic uncomplicated diverticular disease,aged 40-80 years,evaluated in 4 Gastroenter-ology Units,were enrolled.Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B.Treatment A(n = 24 patients) received 1 symbiotic sachet Flortec(Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo.Treatment B(n = 21 patients) received high-fibre diet alone for 6 mo.The primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment.RESULTS:In group A,the proportion of patients with abdominal pain 24 h decreased from 100% at baseline to 35% and 25% after 3 and 6 mo,respectively(P 0.001).In group B the proportion of patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1% after 3 and 6 mo,respectively(P = 0.001).Symptom improvement became statistically significant at 3 and 6 mo in group A and B,respectively.The proportion of patients with abdominal pain 24 h decreased from 60% to 20% then 5% after 3 and 6 mo,respectively in group A(P 0.001) and from 33.3% to 9.5% at both 3 and 6 mo in group B(P = 0.03).In group A the proportion of patients with abdominal bloating significantly decreased from 95% to 60% after 3 mo,and remained stable(65%) at 6-mo follow-up(P = 0.005) while in group B,no significant changes in abdominal bloating was observed(P = 0.11).After 6 mo of treatment,the mean visual analogic scale(VAS) values of both short-lasting abdominal pain(VAS,mean ± SD,group A:4.6 ± 2.1 vs 2.2 ± 0.8,P = 0.02;group B:4.6 ± 2.9 vs 2.0 ± 1.9,P = 0.03) and abdominal bloating(VAS,mean ± SD,group A:5.3 ± 2.2 vs 3.0 ± 1.7,P = 0.005;group B:5.3 ± 3.2 vs 2.3 ± 1.9,P = 0.006) decreased in both groups,whilst the VAS values of prolonged abdominal pain decreased in the Flortec group,but remained unchanged in the high-fibre diet group(VAS,mean ± SD,group A:6.5 ± 1.5 vs 4.5 ± 2.1,P = 0.052;group B:4.5 ± 3.8 vs 5.5 ± 3.5).CONCLUSION:A high-fibre diet is effective in relievingabdominal symptoms in symptomatic uncomplicated diverticular disease.This treatment may be implemented by combining the high-fibre diet with Flortec.     

Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis

AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups： normal control group, model group, baicalin-treated group, and colchicine-treated group. Except for the normal control group, all rats in the other groups were administered with carbon tetrachloride to induce hepatic fibrosis. At the same time, the last two groups were also treated with baicalin or colchicine. At the end of the 8 wk, all animals were sacrificed. Serum alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）, transforming growth factor （TGF）-β1, tumor necrosis factor （TNF）-α, interleukin （IL）-6 and IL-10 were measured. Liver index, hepatic hydroxyproline content and the degree of liver fibrosis were also evaluated. RESULTS： The levels of ALT, AST and liver index in the baicalin-treated group were markedly lower than those in the model group （ALT： 143.88 ± 14.55 U/L vs 193.58± 24.35 U/L; AST： 263.66 ± 44.23 U/L vs 404.37± 68.29 U/L; liver index： 0.033 ± 0.005 vs 0.049± 0.009, P 〈 0.01）. Baicalin therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percentage in liver tissue （P 〈 0.01）. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in the baicalin-treated group compared with the model group, while the production of IL-10 was up-regulated： （TGF-β1：260.21 ± 31.01 pg/mL vs 375.49 ± 57.47 pg/mL; TNF-α： 193.40±15.18 pg/mL vs 260.04 ± 37.70 pg/mL; IL-α：339.87 ± 72.95 pg/mL vs 606.47 ± 130.73 pg/mL; IL-10：506.22 ± 112.07 pg/mL vs 316.95 ± 62.74 pg/mL, P 〈 0.01）. CONCLUSION： Baicalin shows certain therapeutic effects on hepatic fibrosis, probably by immunoregulating the imbalance between profibrotic and antifibrotic cytokines.     

LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway

AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3’-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expres...     

Effectiveness of Saccharomyces boulardii in a rat model of colitis

AIM: To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis.METHODS: Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples.RESULTS: The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.003; 11.95 ± 2.34 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were similar. The mean serum and tissue TNF-α levels were determined to be 12.97 ± 18.90 pg/mL and 21.75 ± 15.04 pg/mL in the control group, 18.25 ± 15.44 pg/mL and 25.27 ± 11.95 pg/mL in the TNBS group, 20.59 ± 16.15 pg/mL and 24.39 ± 13.06 pg/mL in the S. boulardii group, 9.05 ± 5.13 pg/mL and 24.46 ± 10.85 pg/mL in the MP group, and 13.95 ± 10.17 pg/mL and 24.26 ± 10.37 pg/mL in the S. boulardii + MP group. Significant differences in terms of the levels of serum and tissue TNF-α and the macroscopic and microscopic scores were not found between the groups. S. boulardii fungemia was not observed in any of the rats. However, Candida fungemia was detected in one rat (14%) in the TNBS group, two rats (28%) in the S. boulardii group, three rats (50%) in the MP group, and three rats (42%) in S. boulardii + MP group.CONCLUSION: S. boulardii does not demonstrate considerable effects on the DAI, pathological scores, or cytokine levels but does decrease the tissue NO levels.     

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM:To investigate the protective effects of ethyl pyruvate(EP) on acute-on-chronic liver failure(ACLF) in rats.METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP(40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1(HMGB1),alanine transaminase(ALT),tumor necrosis factor-(TNF-),interferon-(IFN-),interleukin(IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin(0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P 0.001),HMGB1(35.42 ± 10.86 g/L vs 2.14 ± 0.27 g/L,P 0.001),ALT(8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P 0.001),TNF-(190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P 0.001),IFN-(715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P 0.001),IL-10(6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L,P 0.001) and IL-18(85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin(0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL,P 0.001) and inflammatory cytokines(11.13 ± 2.58 g/L vs 35.42 ± 10.86 g/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time of ACLF rats(60 h) to 162 h,120 h,102 h and 78 h,respectively(2 = 41.17,P 0.0001).CONCLUSION:EP administration can protect against ACLF in rats,and is a potential and novel therapeutic agent for severe liver injury.     

Biliary fistula after treatment for hydatid disease of the liver:When to intervene

AIM:To determine the outcome of patients with biliary fistula(BF)after treatment for hydatid disease of the liver. METHODS:Between January 2000 and December 2010,out of 301 patients with a diagnosis of hydatid cyst of the liver,282 patients who underwent treatment [either surgery or puncture,aspiration,injection and reaspiration(PAIR)procedure]were analysed.Patients were grouped according to the presence or absence of postoperative biliary fistula(PBF)(PBF vs no-PBF groups,respectively).Preoperative clinical,radiological and laboratory characteristics,operative characteristics including type of surgery,peroperative detection of BF,postoperative drain output,morbidity,mortality and length of hospital stays of patients were compared amongst groups.Multivariate analysis was performed to detect factors predictive of PBF.Receiver operative characteristics(ROC)curve analysis were used to determine ideal cutoff values for those variables found to be significant.A comparison was also made between patients whose fistula closed spontaneously(CS)and those with intervention in order to find predictive fac-tors associated with spontaneous closure. RESULTS:Among 282 patients[median(range)age, 23(16-78)years;77.0%male];210(74.5%)were treated with conservative surgery,33(11.7%)radical surgery and 39(13.8%)underwent percutaneous drainage with PAIR procedure A PBF developed in 46(16.3%) patients,all within 5 d after operation.The maximum cyst diameter and preoperative alkaline phosphatase levels(U/L)were significantly higher in the PBF group than in the no-PBF group[10.5±3.7 U/L vs 8.4±3.5 U/L(P<0.001)and 40.0±235.1 U/Lvs 190.0±167.3 U/L(P=0.02),respectively].Hospitalization time was also significantly longer in the PBF group than in the no-PBF group[37.4±18.0 d vs 22.4±17.9 d(P< 0.001)].A preoperative high alanine aminotransferase level(>40 U/L)and a peroperative attempt for fistula closure were significant predictors of PBF development (P=0.02,95%CI:-0.03-0.5 and P=0.001,95%CI:0.1-0.4),respectively.Comparison of     

Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats

AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury.METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 μg/kg, i.p.), prior to ischemic injury and AGM treatment, and examined histologically and immunostained. Another set of experiments was run to study vascular permeability of the stomach using Evan’s blue dye.RESULTS: AGM markedly reduced Evan’s blue dye extravasation (3.58 ± 0.975 μg/stomach vs 1.175 ± 0.374 μg/stomach, P < 0.05), VEGF (36.87 ± 2.71 pg/100 mg protein vs 48.4 ± 6.53 pg/100 mg protein, P < 0.05) and MCP-1 tissue level (29.5 ± 7 pg/100 mg protein vs 41.17 ± 10.4 pg/100 mg protein, P < 0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals. The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen.CONCLUSION: AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K.