Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM: To compare efficacy of proton pump inhibitors (PPIs) with H₂-receptor antagonists (H₂RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD).METHODS: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%.CONCLUSION: PPI monotherapy improves dysmotility-like symptoms significantly better than H₂RAs plus Proks, and should be the treatment of first choice for Japanese FD.     

Anxiety and depression propensities in patients with acute toxic liver injury

AIM:To investigate anxiety and depression propensities in patients with toxic liver injury.METHODS:The subjects were divided into three groups:a healthy control group(Group 1,n=125),an acute non-toxic liver injury group(Group 2,n=124),and a group with acute toxic liver injury group caused by noncommercial herbal preparations(Group 3,n=126).These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale(HADS),Beck Anxiety Inventory(BAI),Beck Depression Inventory(BDI),and the hypochondriasis scale.RESULTS:The HADS anxiety subscale was 4.9±2.7,5.0±3.0 and 5.6±3.4,in Groups 1,2,and 3,respectively.The HADS depression subscale in Group 3 showed the most significant score(5.2±3.2,6.4±3.4 and 7.2±3.4in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).The BAI and BDI in Group 3showed the most significant score(7.0±6.3 and 6.9±6.9,9.5±8.6 and 8.8±7.3,10.7±7.2 and 11.6±8.5in Groups 1,2,and 3,respectively)(BAI:P<0.01 vs Group 1,P<0.05 vs Group 2)(BDI:P<0.01 vs Group1 and 2).Group 3 showed a significantly higher hypochondriasis score(8.2±6.0,11.6±7.5 and 13.1±6.5in Groups 1,2,and 3,respectively)(P<0.01 vs Group 1,P<0.05 vs Group 2).CONCLUSION:Psychological factors that present vulnerability to the temptation to use alternative medicines,such as herbs and plant preparations,are important for understanding toxic liver injury.     

Gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia

AIM:To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia(FD).METHODS:From June 2008 to November 2009,a total of 1049 patients with FD(65.3%female,mean age42.80±11.64 years)who visited the departments of gastroenterology in Wuhan,Beijing,Shanghai,Guangzhou,and Xi’an,China were referred for this study.All of the patients fulfilled the RomeⅢcriteria for FD.Baseline demographic data,dyspepsia symptoms,anxiety,depression,sleep disorder,and drug treatment were assessed using self-report questionnaires.Patients completed questionnaires at baseline and after1,3,6 and 12 mo follow-up.Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring.Multiple linear regression was done to examine factors associated with outcome,both longitudinally and horizontally.RESULTS:Nine hundred and forty-three patients(89.9%of the original population)completed all four follow-ups.The average duration of follow-up was12.24±0.59 mo.During 1-year follow-up,the mean dyspeptic symptom score(DSS)in FD patients showed a significant gradually reduced trend(P<0.001),and similar differences were found for all individual symptoms(P<0.001).Multiple linear regression analysis showed that sex(P<0.001),anxiety(P=0.018),sleep disorder at 1-year follow-up(P=0.019),weight loss(P<0.001),consulting a physician(P<0.001),and prokinetic use during 1-year follow-up(P=0.035)were horizontally associated with DSS at 1-year followup.No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline.CONCLUSION:Female sex,anxiety,and sleep disorder,weight loss,consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.     

Electrical bioimpedance gastric motility measurement based on an electrical-mechanical composite mechanism

AIM: To introduce a bioimpedance gastric motility measurement method based on an electrical-mechanical composite concept and a preliminary clinical application.METHODS: A noninvasive gastric motility measurement method combining electrogastrogram (EGG) and impedance gastric motility (IGM) test was used. Preliminary clinical application studies of patients with functional dyspepsia (FD) and gastritis, as well as healthy controls, were carried out. Twenty-eight FD patients (mean age 40.9 ± 9.7 years) and 40 healthy volunteers (mean age 30.9 ± 7.9 years) were involved. IGM spectrum was measured for both the healthy subjects and FD patients, and outcomes were compared in the FD patients before treatment and 1 wk and 3 wk after treatment. IGM parameters were obtained from 30 erosive gastritis patients (mean age 50.5 ± 13.0 years) and 40 healthy adults, and IGM and EGG results were compared in the gastritis patients before treatment and 1 wk after treatment.RESULTS: There were significant differences in the IGM parameters between the FD patients and healthy subjects, and FD patients had a poorer gastric motility [percentage of normal frequency (PNF) 70.8 ± 25.5 in healthy subjects and 28.3 ± 16.9 in FD patients, P < 0.01]. After 1 wk administration of domperidone 10 mg, tid, the gastric motility of FD patients was not improved, although the EGG of the patients had returned to normal. After 3 wk of treatment, the IGM rhythm of the FD patients became normal. There was a significant difference in IGM parameters between the two groups (PNF 70.4 ± 25.5 for healthy subjects and 36.1 ± 21.8 for gastritis patients, P < 0.05). The EGG rhythm of the gastritis patients returned to normal (frequency instability coefficient 2.22 ± 0.43 before treatment and 1.77 ± 0.19 one wk after treatment, P < 0.05) after 1 wk of treatment with sodium rabeprazole tablets, 10 mg, qd, po, qm, while some IGM parameters showed a tendency toward improvement but had not reached statistical significance.CONCLUSION: The electrical-mechanical composite measurement method showed an attractive clinical application prospect in gastric motility research and evaluation.     

Outcome and costs of laparoscopic pancreaticoduodenectomy during the initial learning curve vs laparotomy

AIM:To compare laparoscopic pancreaticoduodenectomy(TLPD) during the initial learning curve with open pancreaticoduodenectomy in terms of outcome and costs.METHODS:This is a retrospective review of the consecutive patients who underwent TLPD between December 2009 and April 2014 at our institution.The experiences of the initial 15 consecutive TLPD cases,considered as the initial learning curve of each surgeon,were compared with the same number of consecutive laparotomy cases with the same spectrum of diseases in terms of outcome and costs.Laparoscopic patients with conversion to open surgery were excluded.Preoperative demographic and comorbidity data were obtained.Postoperative data on intestinal movement,pain score,mortality,complications,and costs were obtained for analysis.Complications related to surgery included pneumonia, intra-abdominal abscess,postpancreatectomy hemorrhage,biliary leak,pancreatic fistula,delayed gastric emptying,and multiple organ dysfunction syndrome.The total costs consisted of cost of surgery,anesthesia,and admission examination.RESULTS:A total of 60 patients,including 30 consecutive laparoscopic cases and 30 consecutive open cases,were enrolled for review.Demographic and comorbidity characteristics of the two groups were similar.TLPD required a significantly longer operative time(513.17 ± 56.13 min vs 371.67 ± 85.53 min,P 0.001).The TLPD group had significantly fewer mean numbers of days until bowel sounds returned(2.03 ± 0.55 d vs 3.83 ± 0.59 d,P 0.001) and exhaustion(4.17 ± 0.75 d vs 5.37 ± 0.81 d,P 0.001).The mean visual analogue score on postoperative day 4 was less in the TLPD group(3.5 ± 9.7 vs 4.47 ± 1.11,P 0.05).No differences in surgery-related morbidities and mortality were observed between the two groups.Patients in the TLPD group recovered more quickly and required a shorter hospital stay after surgery(9.97 ± 3.74 d vs 11.87 ± 4.72 d,P 0.05).A significant difference in the total cost was found between the two groups(TLPD 81317.43 ± 2027.60 RMB vs laparotomy 78433.23 ± 5788.12 RMB,P 0.05).TLPD had a statistically higher cost for both surgery(24732.13 ± 929.28 RMB vs 19317.53 ± 795.94 RMB,P 0.001)and anesthesia(6192.37 ± 272.77 RMB vs 5184.10 ± 146.93 RMB,P 0.001),but a reduced cost for admission examination(50392.93 ± 1761.22 RMB vs 53931.60 ± 5556.94 RMB,P 0.05).CONCLUSION:TLPD is safe when performed by experienced pancreatobiliary surgeons during the initial learning curve,but has a higher cost than open pancreaticoduodenectomy.     

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?     

Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

AIM: To investigate the role of the hydrogen-rich water(HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde(MDA), superoxide dismutase(SOD), myeloperoxidase(MPO), interleukin(IL)-06 and tumor necrosis factor(TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2(COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores(4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group(2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues(37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues(46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum(505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues(staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.     

Vitamin D supplementation improves sustained virologic response in chronic hepatitis C （genotype 1）-nave patients

AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy.METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by real-time polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment.RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean body mass index (27 ± 4 kg/m² vs 24 ± 3 kg/m²; P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin.CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-naïve patients with chronic HCV genotype 1 infection significantly improves the viral response.     

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation

Background

Approaches to increase organ availability for orthotopic liver transplantation (OLT) often result in the procurement of marginal livers that are more susceptible to ischaemia, preservation and reperfusion injury (IPRI).

Methods

The effects of post-OLT hyperbaric oxygen (HBO) therapy on IPRI in a syngeneic rat OLT model were examined at various time-points. The effects of IPRI and HBO on hepatocyte necrosis, apoptosis, proliferation, and sinusoidal morphology and ultrastructure were assessed.

Results

Post-OLT HBO therapy significantly reduced the severity of IPRI; both apoptosis [at 12 h: 6.4 ± 0.4% in controls vs. 1.6 ± 0.7% in the HBO treatment group (p < 0.001); at 48 h: 2.4 ± 0.2% in controls vs. 0.4 ± 0.1% in the HBO treatment group (p < 0.001)] and necrosis [at 12 h: 18.7 ± 1.8% in controls vs. 2.4 ± 0.4% in the HBO treatment group (p < 0.001); at 48 h: 8.5 ± 1.3% in controls vs. 3.4 ± 0.9% in the HBO treatment group (P = 0.019)] were decreased. Serum alanine transaminase was reduced [at 12 h: 1068 ± 920 IU/l in controls vs. 370 ± 63 IU/l in the HBO treatment group (P = 0.030); at 48 h: 573 ± 261 IU/l in controls vs. 160 ± 10 IU/l in the HBO treatment group (P = 0.029)]. Treatment with HBO also promoted liver regeneration [proliferation at 12 h: 4.5 ± 0.1% in controls vs. 1.0 ± 0.3% in the HBO treatment group (p < 0.001); at 48 h: 8.6 ± 0.7% in controls vs. 2.9 ± 0.2% in the HBO treatment group (p < 0.01)] and improved sinusoidal diameter and microvascular density index.

Conclusions

Hyperbaric oxygen therapy has persistent positive effects post-OLT that may potentially transfer into clinical practice.     

Therapeutic effect of Streptococcus thermophilus CRL 1190-fermented milk on chronic gastritis

AIM: To investigate the potential therapeutic effect of exopolysaccharide (EPS)-producing Streptococcus thermophilus (S. thermophilus) CRL 1190 fermented milk on chronic gastritis in Balb/c mice.METHODS: Balb/c mice were fed with the fermented milk for 7 d after inducing gastritis with acetyl-salicylic acid (ASA, 400 mg/kg body weight per day for 10 d). Omeprazole was included in this study as a positive therapeutic control. The gastric inflammatory activity was evaluated from gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-γ (INFγ) and tumor necrosis factor-α (TNF-α) cytokine-producing cells in the gastric mucosa, and thickness of the mucus layer.RESULTS: Animals receiving treatment with the EPS-producing S. thermophilus CRL 1190 fermented milk showed a conserved gastric mucosa structure similar to that of healthy animals. Inflammation scores of the fermented milk-treated mice were lower than those of mice in the gastritis group (0.2 ± 0.03 vs 2.0 ± 0.6, P < 0.05). A marked decrease in INFγ⁺ (15 ± 1.0 vs 28 ± 1.2, P < 0.05) and TNF-α⁺ (16 ± 3.0 vs 33 ± 3.0, P < 0.05) cells and an increase in IL-10⁺ (28 ± 1.5 vs 14 ± 1.3, P < 0.05) cells compared to the gastritis group, was observed. Also, an increase in the thickness of the mucus gel layer (2.2 ± 0.6 vs 1.0 ± 0.3; 5.1 ± 0.8 vs 1.5 ± 0.4 in the corpus and antrum mucosa, respectively, P < 0.05) compared with the gastritis group was noted. A milk suspension of the purified EPS from S. thermophilus CRL1190 was also effective as therapy for gastritis.CONCLUSION: This study suggests that fermented milk with S. thermophilus CRL 1190 and/or its EPS could be used in novel functional foods as an alternative natural therapy for chronic gastritis induced by ASA.     

Moxibustion inhibits interleukin-12 and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis

AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC).METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons.RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12).CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response.     

Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statisticall     

Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats

AIM: To investigate the effects of hexahydrocurcumin (HHC), and its combination with 5-fluorouracil (5-FU) on dimethylhydrazine (DMH)-induced colon cancer in rats.METHODS: Male Wistar rats weighing 100-120 g were used as subject models. Aberrant crypt foci (ACF), early preneoplastic lesions of colon cancer, were induced by subcutaneous injection of DHM (40 mg/kg) twice a week for two weeks. After the first DMH injection, rats were treated daily with vehicle (n = 12), curcumin (CUR) (50 mg/kg) (n = 12), HHC (50 mg/kg) orally (n = 12), and treated weekly with an intraperitoneal injection of 5-FU (50 mg/kg) (n = 12), or a combination of 5-FU plus CUR (n = 12) and HHC (n = 12) at the same dosage(s) for 16 wk. The total number of ACF and large ACF were assessed. Cyclooxygenase (COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues. The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted. Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method. Apoptotic index (AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS: The total number of ACF was highest in the DMH-vehicle group (1558.20 ± 17.37), however, the number of ACF was significantly reduced by all treatments, 5-FU (1231.20 ± 25.62 vs 1558.20 ± 17.37, P < 0.001), CUR (1284.20 ± 25.47 vs 1558.20 ± 17.37, P < 0.001), HHC (1086.80 ± 53.47 vs 1558.20 ± 17.37, P < 0.001), DMH-5-FU + CUR (880.20 ± 13.67 vs 1558.20 ± 17.37, P < 0.001) and DMH-5-FU + HHC (665.80 ± 16.64 vs 1558.20 ± 17.37, P < 0.001). Interestingly, the total number of ACF in the combined treatment groups, the DMH-5-FU + CUR group (880.20 ± 13.67 vs 1231.20 ± 25.62, P < 0.001; 880.20 ± 13.67 vs 1284.20 ± 25.47, P < 0.001) and the DMH-5-FU + HHC group (665.80 ± 16.64 vs 1231.20 ± 25.62, P < 0.001; 665.80 ± 16.64 vs 1086.80 ± 53.47, P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone. Large ACF were also significantly reduced in all treatment groups, 5-FU (111.00 ± 7.88 vs 262.20 ± 10.18, P < 0.001), CUR (178.00 ± 7.33 vs 262.20 ± 10.18, P < 0.001), HHC (186.60 ± 21.51 vs 262.20 ± 10.18, P < 0.001), DMH-5-FU + CUR (122.00 ± 5.94 vs 262.20 ± 10.18, P < 0.001) and DMH-5-FU + HHC (119.00 ± 17.92 vs 262.20 ± 10.18, P < 0.001) when compared to the vehicle group. Furthermore, in the DMH-5-FU + CUR and DMH-5-FU + HHC groups the formation of large ACF was significantly reduced when compared to CUR (122.00 ± 5.94 vs 178.00 ± 7.33, P < 0.005) or HHC treatment alone (119.00 ± 17.92 vs 186.60 ± 21.51, P < 0.001), however, this reduction was not statistically different to 5-FU monotherapy (122.00 ± 5.94 vs 111.00 ± 7.88, P = 0.217; 119.00 ± 17.92 vs 111.00 ± 7.88, P = 0.619, respectively). The levels of COX-1 protein after all treatments were not different from normal rats. A marked increase in the expression of COX-2 protein was observed in the DMH-vehicle group. Over-expression of COX-2 was not significantly decreased by 5-FU treatment alone (95.79 ± 1.60 vs 100 ± 0.00, P = 0.198). However, over-expression of COX-2 was significantly suppressed by CUR (77.52 ± 1.68 vs 100 ± 0.00, P < 0.001), HHC (71.33 ± 3.01 vs 100 ± 0.00, P < 0.001), 5-FU + CUR (76.25 ± 3.32 vs 100 ± 0.00, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 100 ± 0.00, P < 0.001) in the treated groups compared to the vehicle group. Moreover, CUR (77.52 ± 1.68 vs 95.79 ± 1.60, P < 0.001), HHC (71.33 ± 3.01 vs 95.79 ± 1.60, P < 0.001), 5-FU + CUR treatments (76.25 ± 3.32 vs 95.79 ± 1.60, P < 0.001) and 5-FU + HHC (68.48 ± 2.24 vs 95.79 ± 1.60, P < 0.001) markedly decreased COX-2 protein expression more than 5-FU alone. Furthermore, the AI in all treated groups, 5-FU (38.86 ± 4.73 vs 23.56 ± 2.12, P = 0.038), CUR (41.78 ± 6.92 vs 23.56 ± 2.12, P < 0.001), HHC (41.06 ± 4.81 vs 23.56 ± 2.12, P < 0.001), 5-FU + CUR (49.05 ± 6.75 vs 23.56 ± 2.12, P < 0.001) and 5-FU + HHC (53.69 ± 8.59 vs 23.56 ± 2.12, P < 0.001) significantly increased when compared to the DMH-vehicle group. However, the AI in the combination treatments, 5-FU + CUR (49.05 ± 6.75 vs 41.78 ± 6.92, P = 0.192; 49.05 ± 6.75 vs 38.86 ± 4.73, P = 0.771) and 5-FU + HHC (53.69 ± 8.59 vs 41.06 ± 4.81, P = 0.379; 53.69 ± 8.59 vs 38.86 ± 4.73, P = 0.245) did not reach significant levels as compared with each treatment alone and 5-FU monotherapy, respectively.CONCLUSION: The combined effects of HHC with 5-FU exhibit a synergistic inhibition by decreasing ACF formation mediated by down-regulation of COX-2 expression.     

Serum adipokines in inflammatory bowel disease

AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.     

Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.     

Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

AIM:To investigate the relationship between donor liver cold preservation,lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation.METHODS:Liver transplantation models were estab-lished using male Wistar rats.Donor livers were pre-served in University of Wisconsin solution at 4 ℃ for different lengths of time.The effect of ammonium pyr-rolidinedithiocarbamate (PDTC) on ALI was also detect-ed.All samples were harvested after 3 h reperfusion.The severity of ALI was evaluated by lung weight/body weight ratio,lung histopathological score,serum nitric oxide (NO) and endothelin (ET)-1 levels,lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels.Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography.RESULTS:With extended donor liver cold preservation time (CPT),lung histopathological scores,serum ET-1 levels,lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21,P 0.001;343.59 ± 53.97 vs 141.53 ± 48.48,P 0.001;0.00687 ± 0.00037 vs 0.00557 ± 0.00056,P 0.001;17.5 ± 3.0 vs 1.3 ± 0.3,P 0.001;10.8 ± 2.3 vs 1.8 ± 0.4,P 0.001),but se-rum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18,P 0.001).The expression of lung phos-phatidylcholine (PC),phosphatidylethanolamine (PE),phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was 120 min,and decreased when CPT was 180 min (PC:1318.89 ± 54.79 vs 1011.18 ± 59.99,P 0.001;PE:1504.45 ± 119.96 vs 1340.80 ± 76.39,P=0.0019;PI:201.23 ± 34.82 vs 185.88 ± 17.04,P=0.2265;PS:300.43 ± 32.95 vs 286.55 ± 55.55,P=0.5054).All these ALI-associated indexes could be partially reversed by PDTC treatment.CONCLUSION:Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decom-pensation stage,and some antioxidants (e.g.,PDTC) may reverse the pathological process partially.     

Yi-Qi-Zeng-Min-Tang, a Chinese medicine, ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabe...     

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.     

Impairment of gastrointestinal quality of life in severely obese patients

AIM:To investigate the common gastro-intestinal symptoms and quality of life in severely obese subjects.METHODS:We prospectively recruited 340 severely obese patients[mean age 30.5±7.8 years;mean body mass index(BMI)42.9±6.1 kg/m2]and 340 healthy persons(mean BMI 23.1±3.8 kg/m2)matched in sex,age,marriage and education.The quality of life was studied using a specific gastrointestinal quality of life index(GIQLI)questionnaire.The 36 items and four functional domains of the GIQLI were compared and analyzed between the groups.The possible correlation of GIQLI scores with specific clinical variables in severely obese patients was assessed by measuring Pearson’s coefficient of correlation.RESULTS:The mean GIQLI score of severely obese patients was lower than the normal control group(108.5±17.1 vs 123.2±14.8,P<0.01).Severely obese patients had decreased scores in the domains of generalhealth,including physical(17.3±6.0 vs 22.4±3.1,P<0.01),emotional(12.6±4.3 vs 16.6±3.1,P<0.01)and social function(14.7±3.9 vs 17.9±2.5,P<0.01),and in the domain of gastrointestinal symptoms(63.9±6.7 vs 66.3±7.2,P<0.05).A significantly decreased score was found in nine items,and there was an increased score in one out of the 19 items in the domain of symptoms of the GIQLI questionnaire.The decreased score in the domain of symptoms was correlated with increasing glycosylated hemoglobin(HbA1c)levels.CONCLUSION:Severe obesity resulted in a significant impairment of the quality of life and caused specific gastrointestinal symptoms compared with normal controls.The development of gastrointestinal symptoms is correlated increasing HbA1c,suggesting that a poor control of hyperglycemia might be the etiology.