p53 antibodies, metallothioneins, and oxidative stress markers in chronic ulcerative colitis with dysplasia

AIM:To investigate the role of p53 antibodies (p53Abs),metallothioneins (MTs) and oxidative stress markers in the early detection of dysplasia in chronic ulcerative colitis (UC).METHODS:The study included 30 UC patients,15 without dysplasia (group Ⅱ) and 15 with dysplasia (group Ⅲ),in addition to 15 healthy volunteers (group Ⅰ,control subjects).The enzyme-linked immunosorbent assay technique was used to measure serum p53Abs and MTs,while advanced oxidation protein products (AOPPs),and reduced glutathione (G...     

Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α

AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 ℃. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; p H of the perfusate was also evaluated; Hi F-1α m RNA and protein expression were analyzed by real time-polymerase chain reaction and ELi SA, respectively. RESULTS: Livers perfused at 10 and 20 ℃ showed no difference in lactate dehydrogenase release after 6 h of perfusion(0.96 ± 0.23 vs 0.93 ± 0.09 m U/min per g) and had lower hepatic damage as compared to 30 and 37 ℃(5.63 ± 0.76 vs 527.69 ± 45.27 m U/min per g, respectively, P s 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃than in livers perfused at 30 and 37 ℃(0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, P s 0.01). No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃(121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/m L, respectively, P s 0.02), and low relative Hi F-1α m RNA(0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, P s 0.05) and protein(3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s 0.05) expression.CONCLUSION: Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃.     

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.     

Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice

AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 ± 3940 vs 30 ± 21, P < 0.05; 6482 ± 4018 vs 146 ± 58, P < 0.05; 24627 ± 10975 vs 1504 ± 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 ± 1810 vs 8355 ± 3940, P < 0.05; 54 ± 39 vs 8355 ± 3940, P < 0.05; 19 ± 9 vs 8355 ± 3940, P < 0.05), AST levels (IU/L) (729 ± 685 vs 6482 ± 4108, P < 0.05; 187 ± 149 vs 6482 ± 4108, P < 0.05; 141 ± 12 vs 6482 ± 4108, P < 0.05) and LDH levels (IU/L) (7220 ± 6317 vs 24 627 ± 10 975, P < 0.05; 1618 ± 719 vs 24 627 ± 10 975, P < 0.05; 1394 ± 469 vs 24 627 ± 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 ± 0.45 vs 2.15 ± 1.07, P > 0.05; 0.59 ± 0.07 vs 2.15 ± 1.07, P < 0.05; 0.47 ± 0.06 vs 2.15 ± 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 ± 0.340 vs 3.306 ± 0.282, P > 0.05; 5.330 ± 0.421 vs 3.306 ± 0.282, P < 0.05; 6.180 ± 0.212 vs 3.306 ± 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION: 5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses.     

Hepatocyte nuclear factor 4α induces a tendency of differentiation and activation of rat hepatic stellate cells

AIM: To investigate the effect of hepatocyte nuclear factor 4α(HNF4α) on the differentiation and transformation of hepatic stellate cells(HSCs).METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4αshRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes.RESULTS: With increased expression of HNF4αmediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells(98.33 ±12.33 vs 41.33 ± 5.67, P 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated(G-P-6:14.34 ± 3.33 vs 42.53 ± 5.87, P 0.01; PEPCK: 10.10± 4.67 vs 56.56 ± 5.25, P 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type Ⅰ collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression,EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated.CONCLUSION: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatmentof liver diseases.     

Protective effect of glutamine on intestinal injury and bacterial community in rats exposed to hypobaric hypoxia environment

AIM:To investigate the protective effect of glutamine(Gln)on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.METHODS:Sprague-Dawley rats were divided into control,hypobaric hypoxia(HH),and hypobaric hypoxia+Gln(5.0 g/kg BW·d)(HG)groups.On the first 3 d,all rats were placed in a normal environment.After the third day,the HH and HG groups were transferred into a hypobaric chamber at a simulated elevation of 7000m for 5 d.The rats in the HG group were given Gln by gavage daily for 8 d.The rats in the control and HH groups were treated with the same volume of saline.The intestinal morphology,serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),interleukin-6 (IL-6),tumor necrosis factor-α(TNF-α),interferon-gamma(IFN-γ)and diamino oxidase(DAO)were examined.We also evaluated the expression levels of occludin,toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65)and myeloid differentiation factor 88(MyD88),and examined the bacterial community in caecal contents.RESULTS:Hypobaric hypoxia induced the enlargement of the heart,liver,lung and kidney,and caused spleen atrophy.Intestinal villi damage was also observed in the HH group.Supplementation with Gln significantly alleviated hypobaric-induced damage to main organs including the intestine,increased serum SOD(1.14±0.03 vs 0.88±0.04,P<0.05)and MDA(8.35±1.60,P<0.01)levels and decreased serum IL-6(1172.13±30.49 vs 1407.05±34.36,P<0.05),TNF-α(77.46±0.78 vs 123.70±3.03,P<0.001),IFN-γ(1355.42±72.80 vs 1830.16±42.07,P<0.01)and DAO(629.30±9.15 vs 524.10±13.34,P<0.001)levels.Moreover,Gln significantly increased occludin(0.72±0.05 vs 0.09±0.01,P<0.001),TLR4(0.15±0.05 vs 0.30±0.09,P<0.05),MyD88(0.32±0.08 vs 0.71±0.06,P<0.01),and NF-κB p65(0.16±0.04 vs 0.44±0.03,P<0.01)expression levels and improved the intestinal bacterial community.CONCLUSION:Gln treatment protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment.These effects may be related to the TLR4/MyD88/NF-κB signaling pathway.     

Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

AIM: To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS: We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes. We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Lepr^db/db mice. A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal). Blood glucose levels and body weights were monitored for 50 d. Glucose and insulin tolerance tests were performed. Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS: Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d, whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic. Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC): 21  508.80 ± 2248.18 vs 62  640.00 ± 5014.28, P < 0.01] and at 6 wk (AUC: 29  956.60 ± 1757.33 vs 60  016.60 ± 3794.47, P < 0.01). In addition, insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC: 9150.17 ± 1007.78 vs 11  994.20 ± 474.40, P < 0.05). The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION: Based on these results, we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.     

Colon transit time according to physical activity and characteristics in South Korean adults

AIM:To investigate factors contributing to the colon transit time(CTT),physical activity and characteristics were examined.METHODS:Forty-seven Korean adults(males,n=23;females,n=24) took a capsule containing 20 radioopaque markers to measure the CTT.The subjects used an accelerometer to measure the physical activity and underwent a bioelectrical impedance analysis to determine the physical characteristics.Macro-nutrient was also surveyed.RESULTS:The mean total CTTs(TCTT) in the males and females were 8.8 and 24.7 h(P=0.002),respectively.In the male subjects,the right CTT(3.5±4.9 h vs 10.0±11.6 h,P=0.023) and recto-sigmoid CTT(4.4±4.7 vs 13.6±12.5 h,P=0.004) were significantly shorter and the total energy expenditure(637.6±44.3 kcal vs 464.3±64.9 kcal,P=0.003),total activity count(247 017±75 022 count vs 178 014±75 998 count,P=0.003),energy expenditure of light intensity(148.5±6.9 kcal vs 120.0±16.8 kcal,P=0.006),energy expenditure of moderate intensity(472.0±36.2 kcal vs 281.4±22.2 kcal,P < 0.001),fat intake(65.5±23.3 g vs 51.2±17.4 g,P=0.010),and water consumption(1714.3±329.4 g vs 1164.7±263.6 g,P=0.009) were significantly higher than in the female subjects.Regarding correlations,when adjusted for gender,fiber(r =-0.545,P < 0.001) and water intake(r =-0.257,P < 0.05) correlated significantly with the TCTT in all subjects.In addition,the body mass index(r =-0.424,P < 0.05) and fiber intake(r =-0.417,P < 0.05) in the males as well as the fiber intake(r =-0.655,P < 0.001) in the females showed significant correlations with the TCTT.CONCLUSION:The subjects showed significant gender differences in the TCTT,right CTT,and recto-sigmoid CTT.Furthermore,the intake of the fiber and water contributed to the CTT.     

Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats

AIM:To investigate whether mesenteric lymph from rats with severe intraperitoneal infection(SII)induces lung injury in healthy rats.METHODS:Twenty adult male specific pathogen-free Wistar rats were divided into two groups.Animals in the SII group received intraperitoneal injection of Escherichia coli(E.coli)at a dose of 0.3 mL/100 g.Control rats underwent the same procedure,but were injected with normal saline rather than E.coli.We ligated and drained the mesenteric lymphatic vessels and collected the mesenteric lymph.Mesenteric lymph collected from SII or control rats was infused intravenously into male healthy rats at a rate of 1 mL/h for 4 h.At the end of the infusion,all rats were sacrificed.Lungs were removed and examined histologically,and wet-to-dry weight(W/D)ratio and myeloperoxidase(MPO)activity were determined.Enzyme-linked immunosorbent assay(ELISA)was performed to determine the levels of the proinflammatory cytokines tumor necrosis factor(TNF)-αand interleukin(IL)-6.We performed Western blot to investigate the activation of Toll-like receptor(TLR)-4,and nuclear factor(NF)-κB p65.RESULTS:Compared with the control infusion group,there were obvious pathological changes in the SII group.The W/D ratio was significantly increased in the SII compared to control infusion group(5.86±0.06vs 5.37±0.06,P<0.01).MPO activity significantly increased in the SII infusion rats with a mean level of0.86±0.02 U/g compared to 0.18±0.05 U/g in the control group(P<0.01).The concentrations of TNF-αand IL-6 were significantly increased in the SII infusion group.The concentration of TNF-αwas significantly increased in the SII infusion rats compared to control infusion rats(2104.46±245.91 vs 1475.13±137.82pg/mL,P<0.01).The concentration of IL-6 was significantly increased in the SII infusion rats with a mean level of 50.56±2.85 pg/mL compared to 43.29±2.02 pg/mL(P<0.01).The expression levels of TLR-4(7496.68±376.43 vs 4589.02±233.16,P<0.01)and NF-κB(8722.19±323.96 vs 6498.91±338.76,P<0.01)were significantly increased in the SII infusion group compared to the control infusion group.The infusion of SII lymph,but not control lymph,caused lung injury.CONCLUSION:The results indicate that SII lymph is sufficient to induce acute lung injury.     

Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression

AIM:To investigate the effects of dihydromyricetin(DHM)on the migration and invasion of human hepatic cancer cells.METHODS:The hepatoma cell lines SK-Hep-1 and MHCC97L were used in this study.The cells were cultured in RPIM-1640 medium supplemented with 10%fetal bovine serum at 37℃in a humidified 5%CO2incubator.DHM was dissolved in dimethyl sulfoxide and diluted to various concentrations in medium before applying to cells.MTT assays were performed to measure the viability of the cells after DHM treatment.Wound healing and Boyden transwell assays were used to assess cancer cell motility.The invasive capacity of cancer cells was measured using Matrigel-coated transwell chambers.Matrix metalloproteinase(MMP)-2/9 activity was examined by fluorescence analysis.Western blot was carried out to analyze the expression of MMP-2,MMP-9,p-38,JNK,ERK1/2 and PKC-δproteins.All data were analyzed by Student’s t tests in GraphPad prism 5.0software and are presented as mean±SD.RESULTS:DHM was found to strongly inhibit the migration of the hepatoma cell lines SK-Hep-1(without DHM,24 h:120±8μmol/L vs 100μmol/L DHM,24h:65±10μmol/L,P<0.001)and MHCC97L(without DHM,24 h:126±7μmol/L vs 100μmol/L DHM,24h:74±6μmol/L,P<0.001).The invasive capacity of the cells was reduced by DHM treatment(SK-Hep-1cells without DHM,24 h:67±4μmol/L vs 100μmol/L DHM,24 h:9±3μmol/L,P<0.001;MHCC97L cells without DHM,24 h:117±8μmol/L vs 100μmol/L DHM,24 h:45±2μmol/L,P<0.001).MMP2/9 activity was also inhibited by DHM exposure(SK-Hep-1 cells without DHM,24 h:600±26μmol/L vs 100μmol/L DHM,24 h:100±6μmol/L,P<0.001;MHCC97L cells without DHM,24 h:504±32μmol/L vs 100μmol/L DHM 24 h:156±10μmol/L,P<0.001).Western blot analysis showed that DHM decreased the expression level of MMP-9 but had little effect on MMP-2.Further investigation indicated that DHM markedly reduced the phosphorylation levels of p38,ERK1/2 and JNK in a concentration-dependent manner but had no impact on the total protein levels.In addition,PKC-δprotein,a key protein in the regulation of MMP family protein expression,was up-regulated with DHM treatment.CONCLUSION:These findings demonstrate that DHM inhibits the migration and invasion of hepatoma cells and may serve as a potential candidate agent for the prevention of HCC metastasis.     

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatm     

Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P 0.001),waist circumference(r =0.356,P 0.001),percent body fat(r = 0.296,P 0.001),systolic blood pressure(r = 0.202,P 0.001),total cholesterol(r = 0.134,P 0.001),triglycerides(r = 0.292,P 0.001),cystatin C(r = 0.069,P 0.001) and uric acid(r = 0.142,P 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P 0.001),waist circumference(r = 0-0.243,P 0.001),percent body fat(r =-0.217,P 0.001),systolic blood pressure(r =-0.132,P 0.001),total cholesterol(r =-0.106,P 0.001),triglycerides(r =-0.205,P 0.001),cystatin C(r =-0.044,P 0.001) and uric acid(r =-0.096,P 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.     

Melatonin attenuates acute pancreatitis-associated lung injury in rats by modulating interleukin 22

AIM:To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.METHODS:Seventy-two male Sprague-Dawley rats were randomly divided into three groups:the sham operation(SO),severe acute pancreatitis(SAP),and melatonin treatment(MT) groups.Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate(4% solution) into the biliopancreatic duct.Melatonin(50 mg/kg) was administered 30 min before pancreatitis was induced,and the severity of pancreatic and pulmonary injuries was evaluated 1,4 and 8 h after induction.Serum samples were collected to measure amylase activities,and lung tissues were removed to measure levels of mRNAs encoding interleukin 22(IL-22) and T helper cell 22(Th22),as well as levels of IL-22.RESULTS:At each time point,levels of mRNAs encoding IL-22 and Th22 were significantly higher(P 0.001) in the MT group than in the SAP group(0.526 ± 0.143 vs 0.156 ± 0.027,respectively,here and throughout,after 1 h;0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h;0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h,0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h;0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h;0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h,respectively) and significantly lower(P 0.001) in the SAP group than in the SO group(0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h;0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h;0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h,0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h;0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h;0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h,respectively).The mean pathological scores for pancreatic tissues in the MT group were significantly higher(P 0.01) than those for samples in the SO group(1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h;2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h;4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h),but were significantly lower(P 0.01) than those for samples in the SAP group at each time point(1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h;2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h;4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h).The severity of SAP increased significantly(P 0.01) over time in the SAP group(1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis;and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis).CONCLUSION:Melatonin protects rats against acute pancreatitis-associated lung injury,probably through the upregulation of IL-22 and Th22,which increases the innate immunity of tissue cells and enhances their regeneration.     

Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

AIM: To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.METHODS: Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n = 20) or tap (n = 20) water controlled drinking. Gallbladder fasting volume at ultrasound, blood vitamin E, oxysterols (7-β-hydroxycholesterol and 7-ketocholesterol), bile acid (BA), triglycerides, total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study. Food consumption, stool frequency and body weight were recorded daily.RESULTS: Blood lipids, oxysterols and vitamin E were not affected by either thermal or tap water consumption. Fasting gallbladder volume was significantly (P < 0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL). Total serum BA concentration was significantly (P < 0.05) higher at the end of the study than at baseline in the TW (5.83 ± 1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap water group (3.41 ± 0.46 μmol vs 2.91 ± 0.56 μmol). The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid. The number of pasta (P < 0.001), meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group. Body weight did not change at the end of the study as compared to baseline in both groups.CONCLUSION: Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.     

Diet of patients after pouch surgery may affect pouch inflammation

AIM:To investigate the diet of pouch patients compared to healthy controls,and to correlate pouch patients’diet with disease behavior.METHODS:Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center.Pouch behavior was determined based on clinical,endoscopic and histological criteria.Healthy age-and sex-matched volunteers were selected from the"MABAT"Israeli Nutrition and Public Health Governmental Study and served as the control group.All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid.Data on Dietary behavior,food avoidance,the use of nutritional supplements,physical activity,smoking habits,and body-mass index(BMI)were also obtained.Pouch patients who had familial adenomatous polyposis(n=3),irritable pouch syndrome(n=4),or patients whose pouch surgery took place less than one year previously(n=5)were excluded from analysis.RESULTS:The pouch patients(n=80)consumed significantly more from the bakery products food group(1.2±1.4 servings/d vs 0.6±1.1 servings/d,P<0.05)and as twice as many servings from the oils and fats(4.8±3.4 servings/d vs 2.4±2 servings/d,P<0.05),and the nuts and seeds food group(0.3±0.6 servings/d vs 0.1±0.4 servings/d,P<0.05)compared to the controls(n=80).The pouch patients consumed significantly more total fat(97.6±40.5 g/d vs 84.4±39 g/d,P<0.05)and fat components[monounsaturated fatty acids(38.4±16.4 g/d vs 30±14 g/d,P<0.001),and saturated fatty acids(30±15.5 g/d vs 28±14.1 g/d,P<0.00)]than the controls.In contrast,the pouch patients consumed significantly fewer carbohydrates(305.5±141.4 g/d vs 369±215.2 g/d,P=0.03),sugars(124±76.2 g/d vs 157.5±90.4 g/d,P=0.01),theobromine(77.8±100 mg/d vs 236.6±244.5 mg/d,P<0.00),retinol(474.4±337.1μg/d vs 832.4±609.6μg/d,P<0.001)and dietary fibers(26.2±15.     

Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats

AIM:To evaluate the ameliorative effect of naringenin(NG)during ulcerative colitis(UC)in rats.METHODS:Rats were treated with three different doses(25,50 and 100 mg/kg per day)of NG and a single dose of mesalazine(MES,300 mg/kg per day)for seven days prior to ulcerative colitis induction by4%acetic acid(AA).Twenty four hours after AA rectal administration,animals were scarified and the colonic tissues were dissected.Colonic mucus content was estimated using Alcian blue dye binding technique.In colon tissues,levels of total glutathione sulphadryls(T-GSH),non-protein sulphadryls(NP-SH)and thiobarbituric acid reactive substances(TBARS)were evaluated.The activities of the antioxidant enzymes,catalase(CAT)and superoxide dismutase(SOD)were measured.Concentrations of nucleic acids(DNA and RNA)and total protein were also estimated in colon tissues.Colonic levels of tumor necrosis factor-(TNF-),interleukin-1(IL-1),interleukin-6(IL-6),prostaglandin E2(PGE2)and nitric oxide(NO)were estimated.In cross section of colitis tissue the histopathological changes were observed.RESULTS:Colonic mucus content was decreased in AA compared to controls(587.09±65.59 mg/kg vs941.78±68.41 mg/kg,P<0.001).AA administration markedly reduced T-GSH(5.25±0.37 nmol/L vs 3.04±0.24 nmol/L,P<0.01),NP-SH(3.16±0.04 nmol/L vs 2.16±0.30 nmol/L,P<0.01),CAT(6.77±0.40 U/mg vs 3.04±0.2 U/mg,P<0.01)and SOD(3.10±0.11U/mg vs 1.77±0.18 U/mg,P<0.01)while TBARS,TNF-,IL-1,IL-6,PGE2 and NO levels(15.09±3.84nmol/L vs 59.90±16.34 nmol/L,P<0.01;113.56±1.91 pg/mg vs 134.24±4.77 pg/mg,P<0.01;209.20±36.38 pg/mg vs 422.19±31.47 pg/mg,P<0.01;250.83±25.09 pg/mg vs 638.58±115.9 pg/mg,P<0.01;248.19±36.98 pg/mg vs 541.74±58.34 pg/mg,P<0.01 and 81.26±2.98 mmol/g vs 101.90±10.73 mmol/g,P<0.001)were increased in colon of rats with UC compared controls respectively.Naringenin supplementation,significantly and dose dependently increased the colonic mucus content.The elevated TBARS levels were significantly decreased(39.35±5.86n     

Prevalence of functional dyspepsia and its subgroups in patients with eating disorders

AIM: To study the prevalence of functional dyspepsia (FD) (Rome III criteria) across eating disorders (ED), obese patients, constitutional thinner and healthy volunteers.METHODS: Twenty patients affected by anorexia nervosa, 6 affected by bulimia nervosa, 10 affected by ED not otherwise specified according to diagnostic and statistical manual of mental disorders, 4th edition, nine constitutional thinner subjects and, thirty-two obese patients were recruited from an outpatients clinic devoted to eating behavior disorders. Twenty-two healthy volunteers matched for age and gender were enrolled as healthy controls. All participants underwent a careful clinical examination. Demographic and anthropometric characteristics were obtained from a structured questionnaires. The presence of FD and, its subgroups, epigastric pain syndrome and postprandial distress syndrome (PDS) were diagnosed according to Rome III criteria. The intensity-frequency score of broader dyspeptic symptoms such as early satiety, epigastric fullness, epigastric pain, epigastric burning, epigastric pressure, belching, nausea and vomiting were studied by a standardized questionnaire (0-6). Analysis of variance and post-hoc Sheffè tests were used for comparisons.RESULTS: 90% of patients affected by anorexia nervosa, 83.3% of patients affected by bulimia nervosa, 90% of patients affected by ED not otherwise specified, 55.6% of constitutionally thin subjects and 18.2% healthy volunteers met the Postprandial Distress Syndrome Criteria (χ², P < 0.001). Only one bulimic patient met the epigastric pain syndrome diagnosis. Postprandial fullness intensity-frequency score was significantly higher in anorexia nervosa, bulimia nervosa and ED not otherwise specified groups compared to the score calculated in the constitutional thinner group (4.15 ± 2.08 vs 1.44 ± 2.35, P = 0.003; 5.00 ± 2.45 vs 1.44 ± 2.35, P = 0.003; 4.10 ± 2.23 vs 1.44 ± 2.35, P = 0.002, respectively), the obese group (4.15 ± 2.08 vs 0.00 ± 0.00, P < 0.001; 5.00 ± 2.45 vs 0.00 ± 0.00, P < 0.001; 4.10 ± 2.23 vs 0.00 ± 0.00, P < 0.001, respectively) and healthy volunteers (4.15 ± 2.08 vs 0.36 ± 0.79, P < 0.001; 5.00 ± 2.45 vs 0.36 ± 0.79, P < 0.001; 4.10 ± 2.23 vs 0.36 ± 0.79, P < 0.001, respectively). Early satiety intensity-frequency score was prominent in anorectic patients compared to bulimic patients (3.85 ± 2.23 vs 1.17 ± 1.83, P = 0.015), obese patients (3.85 ± 2.23 vs 0.00 ± 0.00, P < 0.001) and healthy volunteers (3.85 ± 2.23 vs 0.05 ± 0.21, P < 0.001). Nausea and epigastric pressure were increased in bulimic and ED not otherwise specified patients. Specifically, nausea intensity-frequency-score was significantly higher in bulimia nervosa and ED not otherwise specified patients compared to anorectic patients (3.17 ± 2.56 vs 0.89 ± 1.66, P = 0.04; 2.70 ± 2.91 vs 0.89 ± 1.66, P = 0.05, respectively), constitutional thinner subjects (3.17 ± 2.56 vs 0.00 ± 0.00, P = 0.004; 2.70 ± 2.91 vs 0.00 ± 0.00, P = 0.005, respectively), obese patients (3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001; 3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001 respectively) and, healthy volunteers (3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.002; 3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.001, respectively). Epigastric pressure intensity-frequency score was significantly higher in bulimic and ED not otherwise specified patients compared to constitutional thin subjects (4.67 ± 2.42 vs 1.22 ± 1.72, P = 0.03; 4.20 ± 2.21 vs 1.22 ± 1.72, P = 0.03, respectively), obese patients (4.67 ± 2.42 vs 0.75 ± 1.32, P = 0.001; 4.20 ± 2.21 vs 0.75 ± 1.32, P < 0.001, respectively) and, healthy volunteers (4.67 ± 2.42 vs 0.67 ± 1.46, P = 0.001; 4.20 ± 2.21 vs 0.67 ± 1.46, P = 0.001, respectively). Vomiting was referred in 100% of bulimia nervosa patients, in 20% of ED not otherwise specified patients, in 15% of anorexia nervosa patients, in 22% of constitutional thinner subjects, and, in 5.6% healthy volunteers (χ², P < 0.001).CONCLUSION: PDS is common in eating disorders. Is it mandatory in outpatient gastroenterological clinics to investigate eating disorders in patients with PDS?     

Single-incision vs three-incision laparoscopic cholecystectomy for complicated and uncomplicated acute cholecystitis

AIM:To compare the clinical outcome of single-incision laparoscopic cholecystectomy(SILC)and three-incision laparoscopic cholecystectomy(3ILC)for acute cholecystitis.METHODS:From July 2009 to September 2012,136patients underwent SILC or 3ILC for acute cholecystitis at a tertiary referral hospital.One experienced surgeon performed every procedure using 5 or 10 mm 30-degree laparoscopes,straight instruments,and conventional ports.Five patients with perforated gallbladder and diffuse peritonitis and 23 patients with mild acute cholecystitis were excluded.The remaining 108 patients were divided into complicated and uncomplicated groups according to pathologic findings.Patient demography,clinical data,operative results and complications were recorded and analyzed.RESULTS:Fifty patients with gangrenous cholecystitis,gallbladder empyema,or hydrops were classified as the complicated group,and 58 patients with acute cholecystitis were classified as the uncomplicated group.Twenty-three(46.0%)of the patients in the complicated group(n=50)and 39(67.2%)of the patients in the uncomplicated group(n=58)underwent SILC;all others underwent 3ILC.The postoperative length of hospital stay(PLOS)was significantly shorter in the SILC subgroups than the 3ILC subgroups(3.5±1.1 d vs 4.6±1.3 d,P<0.01 in the complicated group;2.9±1.1 d vs 3.7±1.4 d,P<0.05 in the uncomplicated group).The maximum body temperature recorded at day 1 and at day 2 following the procedure was lower in the SILC subgroups,but the difference reached statistical significance only in the uncomplicated group(37.41±0.56℃vs 37.80±0.72℃,P<0.05 on postoperative day 1;37.10±0.43℃vs 37.57±0.54℃,P<0.01 on postoperative day 2).The operative time,estimated blood loss,postoperative narcotic use,total length of hospital stay,conversion rates,and complication rates were similar in both SILC and 3ILC subgroups.The complicated group had longer operative time(122.2±35.0 min vs 106.6±43.6 min,P<0.05),longer PLOS(4.1±1.3 d vs 3.2±1.2 d,P<0.001),and