Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury

AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation.METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer’s solution with heparin 10  000/μL at 4 °C. In groups I and III, the preservation solution added, respectively, L-arginine or N^G-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining.RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in group I was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in group I were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group I were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-α in group I were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient’s lung tissues was significantly reduced in group I after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in group I. There was diffuse strong expression of ICAM-1 and TNF-α in group III at 3 h after reperfusion.CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.     

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...     

Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma

AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.     

Hepatitis B virus pre S1 deletion is related to viral replication increase and disease progression

AIM:To investigate the clinical implications of hepatitis B virus(HBV) pre S1 deletion.METHODS:We developed a fluorescence resonance energy transfer-based real-time polymerase chain reaction(RT-PCR) that can detect four genotypes(wild type, 15-bp, 18-bp and 21-bp deletion).The PCR method was used in two cohorts of Korean chronic HBV subjects with genotype C infections.Cohort Ⅰ included 292 chronic HBV subjects randomly selected from Cheju National University Hospital(Jeju, South Korea) or Seoul National University Hospital(Seoul, South Korea), and cohort Ⅱ included 90 consecutive chronic HBV carriers recruited from Konkuk University Hospital(Seoul, South Korea); the cohort Ⅱ patients did not have hepatocellular carcinoma or liver cirrhosis.RESULTS:The method proposed in this study identified 341 of 382 samples(89.3%).Deletion variants were identified in 100(29.3%) of the 341 detected samples.In both cohorts, the subjects with deletions had a significantly higher Hepatitis B virus e antigen(HBe Ag)-positive seroprevalence [cohort Ⅰ, wild(51.0%) vs deletion(75.0%), P 0.001; cohort Ⅱ, wild(69.2%) vs deletion(92.9%), P = 0.002] and higher HBV DNA levels [cohort Ⅰ, wild(797.7 pg/m L) vs deletion(1678.9 pg/m L), P = 0.013; cohort Ⅱ, wild(8.3 × 108 copies/m L) vs deletion(2.2 × 109 copies/m L), P = 0.049], compared to subjects with wild type HBV.CONCLUSION:HBV genotype C pre S1 deletion may affect disease progression in chronic HBV subjects through an extended duration of HBe Ag seropositive status and increased HBV replications.     

B1a lymphocytes in the rectal mucosa of ulcerative colitis patients

AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy controls.METHODS:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy controls.CD5 + B cells were analysed by three colour flow cytometry from rectal mucosal samples after mechanical disaggregation by Medimachine.Immunohistochemical analysis of B and T lymphocytes was also performed.Correlations between,on the one hand,rectal B1a cell concentrations and,on the other,erythrocyte sedimentation rate and C-reactive protein levels and clinical,endoscopic and histological disease activity indices were evaluated.RESULTS:Rectal B-lymphocyte (CD19 + /CD45 +) rate and concentration were higher in UC patients compared with those in healthy controls (47.85% ± 3.12% vs 26.10% ± 3.40%,P=0.001 and 501 ± 91 cells/mm 2 vs 117 ± 18 cells/mm 2,P 0.001);Rectal B1a cell density (CD5 + CD19 +) was higher in UC patients than in healthy controls (85 ± 15 cells/mm 2 vs 31 ± 6.7 cells/mm 2,P=0.009).Rectal B1a cell (CD5/CD19 +) rate correlated inversely with endoscopic classification (Rs=-0.637,P 0.05).CONCLUSION:B1a lymphocytes seem to be involved in the pathogenesis of UC,however,the role they play in its early phases and in disease activity,have yet to be defined.     

Clinicopathologic features of remnant gastric cancer over time following distal gastrectomy

AIM: To investigate remnant gastric cancer(RGC) at various times after gastrectomy, and lay a foundation for the management of RGC.METHODS: Sixty-five patients with RGC 2 years and 10 years after gastrectomy(RGC Ⅰ) and forty-nine with RGC 10 years after gastrectomy(RGC Ⅱ) who underwent curative surgery were enrolled in the study.The clinicopathologic factors, surgical outcomes, and prognosis were compared between RGC Ⅰ and RGC Ⅱ.RESULTS: There was no significant difference in surgical outcomes between RGC Ⅰ and RGC Ⅱ. For patients reconstructed with Billroth Ⅱ, significantly more patients were RGC Ⅱ compared with RGC(71.9%vs 21.2%, P 0.001), and more RGC Ⅱ patients had anastomotic site locations compared to RGC Ⅰ(31.0%vs 56.3%, P = 0.038). The five-year survival rates for the patients with RGC Ⅰ and RGC Ⅱ were 37.6%and 47.9%, respectively, but no significant difference was observed. Borrmann type and tumor stage were confirmed to be independent prognostic factors in both groups.CONCLUSION: RGC Ⅱ is located on the anastomotic site in higher frequency and more cases develop after Billroth Ⅱ reconstruction than RGC Ⅰ.     

IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C

AIM:To evaluate the effect of single nucleotide polymorphisms of interleukin(IL)-28B,rs12979860 on progression and treatment response in chronic hepatitis C.METHODS:Patients(n = 64;37 men,27 women;mean age,44 ± 12 years) with chronic hepatitis C,genotype 1,received treatment with peg-interferon plus ribavirin.Genotyping of rs12979860 was performed on peripheral blood DNA.Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment.Serum viral load,aminotransferase activity,and insulin level were measured.Insulin resistance index,body mass index,waist/hip ratio,percentage of body fat and fibrosis progression rate were calculated.Applied dose of interferon and ribavirin,platelet and neutrophil count and hemoglobin level were measured.RESULTS:A sustained virological response(SVR) was significantly associated with IL28B polymorphism(CC vs TT allele:odds ratio(OR),25;CC vs CT allele:OR,5.4),inflammation activity(G 1 vs G 1:OR,3.9),fibrosis(F 1 vs F 1:OR,5.9),platelet count( 200 × 10 9 /L vs 200 × 10 9 /L:OR,4.7;OR in patients with genotype CT:12.8),fatty liver(absence vs presence of steatosis:OR,4.8),insulin resistance index( 2.5 vs 2.5:OR,3.9),and baseline HCV viral load( 10 6 IU/mL vs 10 6 IU/mL:OR,3.0).There was no association with age,sex,aminotransferases activity,body mass index,waist/hip ratio,or percentage body fat.There was borderline significance(P = 0.064) of increased fibrosis in patients with the TT allele,and no differences in the insulin resistance index between groups of patients with CC,CT and TT alleles(P = 0.12).Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605,respectively(P 0.001).Significant differences were found in the insulin resistance index(P = 0.01) between patients with and without steatosis.Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon(P = 0.07).CONCLUSION:IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy.Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.     

Analysis of risk factors for polypoid lesions of gallbladder among health examinees

AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China.METHODS: A total of 11 816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG), blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG.RESULTS: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11 026, P =0.013; 92/403 vs 993/10 328, P = 0.001; 47/448 vs 332/10 989, P = 0.001; 32/463 vs 381/10 940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10 224, P = 0.102; 52/443 vs 982/10 339, P = 0.158; 17/478 vs 295/11 026, P = 0.26; 24/471 vs 395/10 926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex.CONCLUSION: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.     

Esophagogastroduodenoscopy with conscious sedation does not interfere with catheter-based 24-h pH monitoring

AIM:To investigate the impact of esophagogastroduodenoscopy with conscious sedation on the subsequent 24-h catheter-based pH monitoring.METHODS:Fifty patients with extra-esophageal symptoms of gastroesophageal reflux disease undergoing ambulatory dual-probe 24-h pH monitoring were enrolled from March 2010 to August 2011.All of the data were collected prospectively and analyzed retrospectively.Thirty-six patients(72%,group A) underwent pH monitoring shortly after esophagogastroduodenoscopy(EGD) with conscious sedation,and 14 patients(28%,group B) underwent pH monitoring without conscious sedation.The 24-h pH data from two time periods were analyzed:the first 4 h(Period Ⅰ) and the remaining time of the study(Period Ⅱ).RESULTS:The mean age of the patients was 49.6 ± 12.5 years;20 patients(40%) were men.The baseline data,including age,sex,body mass index,reflux esophagitis,the Reflux Symptom Index,and the Reflux Findings Score,were comparable between the two groups.The percentage of total time with a pH < 4 and the frequency of acid reflux during Period Ⅰ were not significantly different between the two groups,as measured using both pharyngeal(0.03% ± 0.10% vs 0.07% ± 0.16%,P = 0.32;and 0.07 ± 0.23 episodes/h vs 0.18 ± 0.47 episodes/h,P = 0.33,respectively) and esophageal probes(0.96% ± 1.89% vs 0.42% ± 0.81%,P = 0.59;and 0.74 ± 1.51 episodes/h vs 0.63 ± 0.97 episodes/h,P = 0.49,respectively).The percentage of total time with a pH < 4 and the frequency of acid reflux were also not significantly different between Periods I and Ⅱ in group A patients,as measured using both pharyngeal(0.03% ± 0.10% vs 0.23% ± 0.85%,P = 0.21;and 0.07 ± 0.23 episodes/h vs 0.29 ± 0.98 episodes/h,P = 0.22,respectively) and esophageal probes(0.96% ± 1.89% vs 1.11% ± 2.57%,P = 0.55;and 0.74 ± 1.51 episodes/h vs 0.81 ± 1.76 episodes/h,P = 0.55,respectively).CONCLUSION:EGD with conscious sedation does not interfere with the results of subsequent 24-h pH monitoring in patients with extra-esophageal symptoms of gast     

Role of ascites adenosine deaminase in differentiating between tuberculous peritonitis and peritoneal carcinomatosis

AIM: To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC).METHODS: A retrospective analysis of data was performed on consecutive patients who underwent peritoneoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy.RESULTS: Serum c-reactive protein (7.88 ± 6.62 mg/dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serum-ascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively.CONCLUSION: Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.     

Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer

AIM: To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage II gastric cancer.METHODS: From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN) dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection), and compared for 5-year overall survival by univariate and multivariate analysis.RESULTS: The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years). The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269) and 42.5% (71/167) in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%), there was neither a histopathologically detectable LBVI nor LN metastases (LBVI⁻/LN⁻, group I); in 51 patients (11.7%), LBVI with no evidence of LN metastases was detected (LBVI⁺/LN⁻, group II). In 167 patients (38.3%), LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22.0%) (LBVI⁻/LN⁺, group III), and was determined in 71 patients (16.3%) (LBVI⁺/LN⁺, group IV). Correlation analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI (P < 0.001). The overall 5-year survival was significantly longer in LN-negative patients compared with LN-positive patients (56.1% vs 42.3%, P = 0.015). There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI-negative tumors (39.6% vs 54.8%, P = 0.006). Overall 5-year survival rates in each group were 58.8% (I), 45.8% (II), 45.7% (III) and 36.9% (IV), and there was a significant difference in overall survival between the four groups (P = 0.009). Multivariate analysis in stage II gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508).CONCLUSION: In LN-negative stage II gastric cancer patients, LBVI is an additional independent prognostic marker, and may provide useful information to identify patients with poorer prognosis.     

Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic outpatients

AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesisMETHODS: From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration.RESULTS: SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 μmol/L vs 96.3 ± 143.3 μmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients.CONCLUSION: In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.     

Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients

AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group I included 25 patients with SBP and group II included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin (IL)-10 levels in both blood and ascitic fluid.RESULTS: A significant MCP-1 gene polymorphism was detected in groups I and II (P = 0.001 and 0.02 respectively). Group I was associated with a significantly higher frequency of AG genotype [control 8 (40%) vs SBP 19 (76.0%), P < 0.001], and group II was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1 (5%) vs cirrhotic 16 (64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups (I and II) [control 10 (25%) vs SBP 27 (54%), P < 0.001 and vs cirrhotic 37 (74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group I than in group II. Group I showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy.CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.     

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.     

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.     

Absolute lymphocyte count as a surrogate marker for CD4+ cell count in monitoring of antiretroviral therapy,Northwest Ethiopia: retrospective evaluation

Objective

To determine the use of total lymphocyte count as a surrogate marker for CD4+ cell count among HIV infected patients at the University of Gondar Hospital.

Methods

A retrospective cross sectional study was conducted at the University of Gondar Hospital antiretroviral therapy laboratory from December 2011 to May 2012. Data on CD4+ cell count, total lymphocyte count, sex, and age were collected from 2964 HIV infected patients and analyzed using SPSS version 16 computer software.

Results

Total lymphocyte count was significantly correlated with CD4+ cell count (P<0.001; r²=0.434). The sensitivity, specificity, positive predictive value, negative predictive value of total lymphocyte count<1 200 cells/mm³ to predict CD4+ cell count <200 cells/mm³ was 57.8%, 86.4%%, 34.1%, 86.39%, respectively. A total lymphocyte count<1 000cells/mm³ was found to have suboptimal sensitivity (69.0%), and specificity (85.0%) for predicting a CD4+ cell count <200 cells/mm³.

Conclusions

Total lymphocyte count and CD4+ cell count was positively correlated. Hence, lymphocyte count less than or equal to 1 000/mm³ can be used as a cutoff value in place where there is no CD4+ cell counting machine.     

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

AIM:To assess the effect of Helicobacter pylori(H.pylori)eradication on platelet counts in patients with chronic immune thrombocytopenic purpura(cITP).METHODS:A total of 36 cITP patients were included in the study.The diagnosis of H.pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen.All H.pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk.Patients who continued to be positive for H.pylori on second endoscopyreceived second line salvage therapy.All the patients were assessed for platelet response at 6 wk,3rd and 6th months.RESULTS:Of the 36 patients,17 were positive for H.pylori infection and eradication was achieved in16 patients.The mean baseline platelet count in the eradicated patients was 88615.38±30117.93/mm3and platelet count after eradication at 6 wk,3 mo and6 mo was 143230.77±52437.51/mm3(P=0.003),152562.50±52892.3/mm3(P=0.0001),150187.50±41796.68/mm3(P=0.0001)respectively and in the negative patients,the mean baseline count was71000.00±33216.46/mm3 and at 6 wk,3rd and 6th month follow up was 137631.58±74364.13/mm3(P=0.001),125578.95±71472.1/mm3(P=0.005),77210.53±56892.28/mm3(P=0.684)respectively.CONCLUSION:Eradication of H.pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy.     

Esophagojejunostomy after laparoscopic total gastrectomy by Or VilTM or hemi-double stapling technique

AIM: To investigate the feasibility, advantages and disadvantages of two types of anvil insertion techniques for esophagojejunostomy after laparoscopic total gastrectomy.METHODS: This was an open-label prospective cohort study. Laparoscopy-assisted radical total gastrectomy with D2 lymph node dissection was performed in 84 patients with primary non-metastatic gastric cancer confirmed by pre-operative histological examination. Overweight patients were excluded, as well as patients with peritoneal dissemination and invasion of adjacent organs. After total gastrectomy, all patients were randomized into two groups. Patients in Group Ⅰ underwent esophagojejunostomy using a transorally-inserted anvil(Or VilTM), while patients in Group Ⅱ underwent esophagojejunostomy using the hemi-double stapling technique(HDST). Both types of esophagojejunostomy were performed under laparoscopy. Patients' baseline characteristics, preoperative characteristics, perioperative characteristics, short-term postoperative outcomes and operation cost were comparedbetween the two groups. The primary endpoint was evaluation of the surgical outcome(operating time, time of digestive tract reconstruction and time of anvil insertion) and the medical cost of each operation(operation cost and total cost of hospitalization). The secondary endpoints were time to solid diet, post-surgical hospitalization time, time to defecation, time to ambulation and intra-operative blood loss. In addition, complications were assessed and compared. RESULTS: Laparoscopic total gastrectomy and esophagojejunostomy were successfully performed in all 84 patients, without conversion to laparotomy. There were no significant differences in the operative time and time for total gastrectomy between the two groups(287.8 ± 38.4 min vs 271.8 ± 46.1 min, P = 0.09, and 147.7 ± 31.6 min vs 159.8 ± 33.8 min, P = 0.09, respectively). The time for digestive tract reconstruction and for anvil insertion were significantly decreased in Group Ⅱ compared with Group I(47.8 ± 12.1 min vs 55.4 ± 15.7 min, P = 0.01, and 12.6 ± 4.7 min vs 18.7 ± 7.5 min, P = 0.001, respectively). Intraoperative blood loss(96.4 ± 32.7 m L vs 88.2 ± 36.9 m L, P = 0.28), time to defecation(3.5 ± 0.9 d vs 3.2 ± 1.1 d, P = 0.12), time to ambulation(3.9 ± 0.7 d vs 3.6 ± 1.1 d, P = 0.12), time to solid diet(7.6 ± 1.4 d vs 8.0 ± 2.7 d, P = 0.31) and total hospitalization(10.6 ± 2.6 d vs 10.8 ± 3.5 d, P = 0.80) were similar between the two groups. In addition, the total costs of hospitalization were similar between the two groups(73848.7 ± 11781.0 RMB vs 70870.3 ± 14003.5 RMB, P = 0.296), but operation cost was significantly higher in Group I compared with Group Ⅱ(32401.9 ± 1981.6 RMB vs 26961.9 ± 2293.8 RMB, P 0.001).CONCLUSION: Anvil insertion was faster and easier using the HDST technique compared with Or VilTM, and was more cost-effective. There was no significant difference in safety.     

Curcumin protects against acetaminophen-induced apoptosis in hepatic injury

AIM:To explore the effects of curcumin(CMN)on hepatic injury induced by acetaminophen(APAP)in vivo.METHODS:Male mice were randomly divided into three groups:groupⅠ(control)mice received the equivalent volumes of phosphate-buffered saline(PBS)intraperitoneally(ip);GroupⅡ[APAP+carboxymethylcellulose(CMC)]mice received 1%CMC(vehicle)2h before APAP injection;GroupⅢ(APAP+CMN)mice received curcumin(10 or 20 mg/kg,ip)2 h before before or after APAP challenge.In GroupsⅡandⅢ,APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg.CMN was dissolved in 1%CMC.Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase(ALT)levels in serum and malondialdehyde(MDA)accumulation,superoxide dismutase(SOD)activity and hepatocyte apoptosis in liver tissues.RESULTS:Both pre-and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group(10 mg/kg:801.46±661.34 U/L;20 mg/kg:99.68±86.48 U/L vs 5406.80±1785.75 U/L,P<0.001,respectively).The incidence of liver necrosis was significantly lowered in CMN treated animals.MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group,but increased in APAP treated group(10.96±0.87 nmol/mg protein vs 16.03±2.58 nmol/mg protein,P<0.05).The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected(24.54±4.95 U/mg protein vs 50.21±1.93 U/mg protein,P<0.05).Furthermore,CMN treatment efficiently protected against APAPinduced apoptosis via increasing Bcl-2/Bax ratio.CONCLUSION:CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.