[Levofloxacin-based triple therapy for first-line Helicobacter pylori eradication treatment: a multi-central, randomized, controlled clinical study].

OBJECTIVE: To compare efficacy and tolerability of 7-day standard triple therapy versus 7-day levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori (H. pylori) infection. METHODS: Three hundred consecutive H.pylori positive patients were randomized to receive: clarithromycin, amoxicillin, lansoprazole (Group A: n = 150); or amoxicillin, levofloxacin, lansoprazole (Group B: n = 150). H. pylori status was rechecked by (13)C-urea breath test 4 weeks after the end of therapy. RESULTS: The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 74.5% (111/149) and 78.2% (111/142); and Group B, 82.4% (122/148) and 83.0%(122/147). Although the eradication rate achieved with levofloxacin-based triple therapy was higher than that with standard therapies in either ITT or PP analysis, but no significantly difference was found between the two triple therapies. The incidence of side effects was similar among groups. CONCLUSIONS: A 7-day levofloxacin-based triple therapy can achieve higher H.pylori eradication rate than standard regimen. The levofloxacin-based regimen can be one effective therapy for the first-line anti-H.pylori treatment.

Endoscopic removal of an accidentally swallowed toothbrush.

A rare case is reported with a large foreign body in the upper gastrointestinal tract. A 19-year-old girl accidentally swallowed her toothbrush which was successfully removed via endoscopy using a polypectomy snare under topical pharyngeal anesthesia. The extracted toothbrush was 20 cm long, and it had the characteristic radiographic image.

Ascorbic acid alleviates pancreatic damage induced by dibutyltin dichloride (DBTC) in rats.

PURPOSE: Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. MATERIALS AND METHODS: CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10 mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. RESULTS: Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). CONCLUSION: Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP.

Plasma level of thrombomodulin is an early indication of pancreatic necrosis in patients with acute pancreatitis.

BACKGROUND: The potential to predict pancreatic necrosis within the first 48 h by using plasma soluble thrombomodulin (sTM) in 104 patients with acute pancreatitis (AP) was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to Balthazar CT grade, pancreatitis was classified as no necrosis in 72 patients, one-third necrotic in 18 patients, one-half necrotic in 10 patients and more than one-half necrotic in 4 patients. Blood was collected at the first 48 hours after the onset of pain and analyzed for sTM. RESULTS: In the healthy volunteers, plasma levels of TM were 16.49+/-5.24 microg/L. By comparison, the mean plasma levels of TM in each group of pancreatitis patients were as follows: CT grade A group, 34.21+/-10.73 microg/L; CT grade B group, 36.18+/-12.50 microg/L; CT grade C group, 49.39+/-18.38 microg/L; CT grade D group, 114.46+/-39.44 microg/L; CT grade E group, 100.22+/-15.97 microg/L (p<0.01). And for the patients, the Pearson correlation coefficient between the CT grade and TM values was 0.784 (p<0.01). No necrosis group, 39.22+/-13.75 microg/L; one-third necrotic group, 71.44+/-18.02 microg/L; one-half necrotic group, 123.50+/-28.57 microg/L; more than one-half necrotic group, 129.00+/-33.28 microg/L (p<0.01); And for the patients, the Pearson correlation coefficient between the degree of necrosis and TM values was 0.888 (p<0.01). ROC analysis indicated the area under the ROC curve (AUC +/- SE) for sTM was 0.949+/-0.020, clearly supportive of the high accuracy of this index in predicting the necrosis of AP. CONCLUSION: Plasma soluble thrombomodulin (sTM) is a potential marker to predict pancreatic necrosis within the first 48 h, and further investigation in a multicentre study is necessary.

Effect of emodin on pancreatic fibrosis in rats.

AIM: To establish the rats model of chronic fibrosing pancreatitis and to prove the anti-fibrotic effect of emodin in chronic pancreatitis with fibrosis. METHODS: Fifty rats were randomly divided into five groups, 10 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was infused into the pancreatic duct to induce chronic pancreatitis in rats (except for normal group). Emodin-treated rats were fed with different doses of emodin (20, 40 and 80 mg/kg body weight) for 28 d, while normal group and control group received 0.9% sodium chloride solution. Serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. Histopathological alterations were studied by optical microscopy. Expression of collagen was also examined while transforming growth factor-beta-1 (TGF-beta(1)) was localized by immunochemistry. RESULTS: In emodin-treated rats, the serum levels of HA and LN were decreased significantly (HA, 62.2 +/- 19.3 microg/L vs 112.7 +/- 26.5 microg/L, P < 0.05; LN 44.3 +/- 10.4 microg/L vs 86.2 +/- 16.5 microg/L, P < 0.05); the degree of fibrosis was ameliorated observably; the expression of collagen in pancreatic tissue was reduced especially in high-dose emodin-treated group (36% +/- 5% vs 42% +/- 6%, P < 0.05); with the increased doses of emodin, the expression of TGF-beta(1) was declined, compared with those in control group. CONCLUSION: Emodin has an anti-fibrotic effect on pancreatic fibrosis in rats. Because of its anti-fibrotic effect, it could be a potential herb for the treatment of chronic pancreatitis.

[Effect of emodin on pancreatic fibrosis: experiment with rats].

OBJECTIVE: To study the effect of emodin on pancreatic fibrosis and potential mechanism thereof. METHODS: Fifty SD rats were randomly divided into 5 equal groups: normal control group, model control group, low-dose emodin-treated group, mediate-dose emodin-treated group, and high-dose emodin-treated group. The rats of the latter 4 groups underwent infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct so as to establish models of pancreatic fibrosis. The emodin-treated rats were fed with different doses of emodin (20, 40, and 80 mg/kg body weight), while the normal and model control groups received 0.9% sodium chloride solution instead. Twenty-eight days later the rats were killed, blood samples were collected, and their pancreases were taken out. The serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. The histopathological alterations were studied by optical microscopy. The expression of collagen was examined by Van Gieson staining. Western blotting was used to detect the protein expression of transforming growth factor-beta(1) (TGF-beta(1)). RESULTS: (1) The serum level of HA of the low-dose, mediate-dose, and high-dose emodin-treated groups were 87 microg/L +/- 22 microg/L, 78 microg/L +/- 25 microg/L, and 62 microg/L +/- 19 microg/L respectively, all significantly lower than that of the model control group (113 microg/L +/- 27 microg/L, P < 0.05 or < 0.01). The serum levels of laminin in the low-dose, mediate-dose, and high-dose emodin-treated groups were 67 microg/L +/- 14 microg/L, 57 microg/L +/- 12 microg/L, and 44 microg/L +/- 10 microg/L respectively, all significantly lower than that of the model control group (86 microg/L +/- 17 microg/L, P < 0.05 or P < 0.01); (2) The degrees of fibrosis of the emodin-treated groups were obviously ameliorated in comparison with the model control group, the higher the dose of emodin the more improved the pathological changes, especially in the high-dose emodin-treated group (P < 0.05). (3) The percentages of collagen positive cells of the low-dose, mediate-dose, and high-dose emodin-treated groups were 39% +/- 7%, 38% +/- 4%, and 36% +/- 5% respectively, all lower than that of the model control group (42% +/- 6%), with a significant difference between the high-dose emodin-treated group and the model control group (P < 0.05). (4) The protein content of TGF-beta(1) of the low-dose, mediate-dose, and high-dose emodin-treated groups were 44.3% +/- 2.1%, 39.2% +/- 1.8%, and 28.8% +/- 1.6% respectively, all significantly lower than that of the model control group (60.7% +/- 1.7%, all P < 0.05), and the protein content of TGF-beta(1) of the high-dose emodin-treated group was significantly lower than those of the other 2 emodin-treated groups (both P < 0.05). CONCLUSION: Emoidn has an anti-fibrosis effect on pancreatic fibrosis, which maybe related to the content of TGF-beta(1) protein.

[Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper esophagus].

OBJECTIVE: To determine accurately the incidence of heterotopic gastric mucosa in the upper esophagus (HGMUE) in China, and to study the macroscopic and microscopic aspects of the lesions and to evaluate the clinical importance of HGMUE. METHODS: A prospective study was made among a total of 15,228 consecutive patients, 8,573 male and 6,655 female, aged 54 (8-95), undergoing gastroscopy. Disease histories of all patients were carefully inquired, especially those regarding possible complaints including discomfort of throat and swallowing pain and so on. Special care was taken in the upper esophageal sphincter area to make sure whether the area was adequately inspected. Biopsy specimens from aberrant mucosa were obtained and the sections were stained with haematoxylin and eosin, and Giemsa stain for Helicobacter pylori. RESULTS: HGMUE was found in 39 patients (0.26%) with an average age of 50. Five patients with H. pylori infection in heterotopic gastric mucosa also presented the infection in the stomach. The gastric mucosa was gastric body type in 8 patients, transitional type in 11 patients, and antral pattern in 7 patients. Intestinal metaplasia was found in 5 patients, and mild atypical hyperplasia in 2 patients. An impressive finding was coexistent erosive gastritis in 14 patients (35.9%), Barrett's esophagus in one patient (2.6%), peptic ulcer in 8 patients (20.5%), and a patient had the complication of constriction in the upper esophagus. CONCLUSION: HGMUE is not rare in China. The presence of inlet patches is possibly correlated with specific symptoms. There are some severe complications in HGMUE, especially esophageal constriction. Close surveillance should be taken for rare cases with metaplasia or dysplasia in HGMUE.

Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients.

AIM: To characterize the CagA variable region of Helicobacter pylori isolates from Chinese patients. METHODS: DNA fragments in CagA variable region were amplified and sequenced respectively from genomic DNA of 19 isolates from patients with gastric cancer and 20 isolates from patients with chronic gastritis. The tendency of phosphorylation in tyrosine(s) of CagA proteins was evaluated subsequently by phosphorylation assay in vivo and in vitro respectively. RESULTS: About 97.44% (38/39) H pylori isolates possessed CagA gene. CagA(+) strains contained 2-4 tandem five-amino-acid motifs EPIYA but only one EPIYA had repeated sequence in CagA variable region in different isolates. There was no significant difference between the number of EPIYA motifs in H pylori from patients with different diseases. However, only tyrosine site in EPIYA within repeated sequence could be phosphorylated by AGS cells in vivo although all tyrosine sites in EPIYA could be phosphorylated in vitro. CONCLUSION: CagA in Chinese has no functional difference in perturbing cellular signal pathway among different H pylori isolates.

Biological activity of the virulence factor cagA of Helicobacter pylori.

BACKGROUND: China is one of the countries with the highest incidence of H. pylori and more than 9090 isolates possessed the cagA gene. This study was to evaluate the biological activity of the H. pylori virulence factor cagA isolated from Chinese patients. METHODS: cagA DNA fragments were amplified from the genomic DNA and subsequently cloned into the mammalian expression vector for cell transfection and DNA sequencing. cagA protein, phosphorylated-tyrosine cagA and the complex of cagA precipitated with SHP-2 were identified respectively by western blot in the crude cell lysate from conditionally immortalized gastric epithelial cells at 48 hours after transfection with cagA DNA. In addition, the ability of induction of scattering phenotype was examined after transient expression of cagA in AGS cells. RESULTS: The C-terminal half of cagA contained only one repeated sequence and three tandem five-amino-acid motifs glutamic acid-proline-isoleucine-tyrosine-alanine (EPIYA). Moreover, the amino acid sequence of D2 region in repeated sequence was aspartic acid-phenylanaline-aspartic acid (D-F-D) which was significantly distinguished from the three repeated sequences and aspartic acid-aspartic adid-leucine (D-D-L) in the western standard strain NCTC11637. Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells. Transient expression of cagA in AGS cells showed that cagA was able to induce the elongation phenotype although to a lesser extent than western strains. CONCLUSIONS: cagA perturbs cell signaling pathways by binding with SHP-2. However, significant difference exists in amino acid sequence and biological function of cagA in Chinese compared with those of western countries.

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer.

AIM: To investigate the clinical significance of the expression of VEGF165mRNA and the correlation with vascular endothelial growth factor (VEGF) protein and inducible nitric oxide synthase (iNO) in human gastric cancer. METHODS: We tested VEGF165mRNA expression in 31 cases of resected gastric cancer specimens and normal paired gastric mucosae by RT-PCR. Total RNA was extracted with TRIzol reagents, transcribed into cDNA with oligo (dT15) priming, inner controlled with beta-actin expression and agarose gel isolated after PCR. VEGF expression was quantitated with IS1000 imaging system. Meanwhile we also examined expression levels of VEGF protein and iNOS in 85 cases of gastric cancer. All paraffin-embedded samples were immunohistochemically stained by streptavidin -peroxidase method (SP). RESULTS: The mean expression of VEGF165mRNA in gastric cancer was 1.125+/-0.356, significantly higher than that of normal paired mucosae, which was 0.760+/-0.278. The data indicated that the expression level of VEGF165mRNA was well related to lymph node metastasis and TNM stages of UICC. The expression levels in patients with lymph node metastasis and without lymph node metastasis were 1.219+/-0.377 and 0.927+/-0.205 respectively (P<0.05). The expression in stages I, II, III, IV was 0.934+/-0.194, 1.262+/-0.386 respectively (P<0.01). Further analysis showed the lymph node metastasis rate in the group with over-expression of VEGF was higher than that in the group with low expression of VEGF (83.3% vs 46.2%), and the ratio of stage III+IV in the group with over-expression of VEGF was also higher than that in the group with low expression with VEGF (77.8% vs 33.8%) (P<0.05). The positive rates of expression of VEGF protein and iNOS in 85 cases of gastric cancer were 75.4% and 58.8% respectively, and 50.1% of the patients showed positive staining both for iNOS and VEGF, the correlation with the two factors was significant (P=0.018). But more intensive analysis showed the immunoreactive grades of VEGF were not associated with that of iNOS. CONCLUSIONS: The expression of VEGF165mRNA is well related with lymph node metastasis and TNM stages of UICC in gastric cancer, and is concerned with the invasiveness and metastasis of gastric cancer. The relationship can be observed between the expression of VEGF and iNOS in gastric cancer.

Distribution of H.pylori antigens in gastric mucosa and its significance.

OBJECTIVE: To investigate the distribution of H.pylori antigens in the gastric mucosa in patients with H.pylori infection, and the relationship between the distribution and gastric cancer. METHODS: Of 112 patients confirmed by pathological study to have chronic superficial gastritis, precancerous changes (chronic atrophic gastritis, intestinal metaplasia or atypical hyperplasia) and gastric cancer, 28 were H.pylori negative and 84 were H.pylori positive. H.pylori antigens in the gastric mucosa were detected by immunohistochemistry. RESULTS: The H.pylori positive group, comprised 12 of 22 (50.0%) in the chronic superficial gastritis group, 22 of 25 (88.0%) in the precancerous changes group and 13 of 35 (37.1%) in the gastric cancer group. The positive rates of H.pylori antigens in the cytoplasm progressively increased, respectively at 0.0% (0/12), 63.6% (14/22) and 84.6% (11/13) for the same groups (chi(2)=19.76, P=0.000); H.pylori antigens were located in the mucus layer and above the neck of the mucosal gland in 9 of 12 (75.0%) cases with chronic superficial gastritis, at the neck of the mucosal gland and the isthmus in 12 of 22 (54.5%) cases with precancerous changes, below the isthmus in 9 of 13 (69.2%) cases with gastric cancer (chi(2)=25.30, P=0.000). In the H.pylori negative group, no H.pylori antigen was observed. CONCLUSION: With the progression of chronic superficial gastritis-->precancerous changes-->gastric cancer, H.pylori antigens progressively migrated from the outer part to the inner part of the cell, and from the superficial to the deep gastric mucosa.

[Effect of selective cyclooxygenase-2 inhibitor celebrex on expression of vascular endothelial growth factor (VEGF) in pancreatic carcinoma].

BACKGROUND & OBJECTIVE: The previous study has identified that cyclooxygenase-2 (COX-2) may have a close relation with tumor genesis, particularly with digestive tract tumors, and its inhibitor can exert the chemoprevention role on carcinogenesis. This study was designed to investigate the effect of celebrex, a selective cyclooxygenase-2 inhibitor, on the expression of vascular endothelial growth factor (VEGF) in pancreatic carcinoma of xenografted nude mice induced by pancreatic carcinoma PC-3 cell lines. METHODS: The effect of celebrex on tumor growth was observed.The expression of VEGF in the tumors was determined by reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Average tumor volume and tumor weight from control mice were 0.438+/-0.052 cm(3) and 0.552+/-0.064 g as compared with 0.215+/-0.038 cm(3) and 0.244+/-0.042 g from treated mice (inhibition rate:51.6%,P< 0.05). VEGF expression was significantly down-regulated in the celebrex-treated tumors. ELISA revealed that the expression levels of VEGF were 1.11+/-0.11(microg/g) in control mice and the 0.66+/-0.11(microg/g) in the treated mice. The inhibition rate of VEGF was 40.6% (P< 0.05). CONCLUSION: COX-2 may play an important role in the angiogenesis of pancreatic carcinoma. The selective COX-2 inhibitor, celebrex, can result in the inhibition of angiogenesis and tumor growth.

[Plasma levels of ascorbic acid and vitamin E in patients with liver cirrhosis].

OBJECTIVE: To investigate the plasma levels of ascorbic acid and vitamin E in patients with liver cirrhosis and to explore their significance. METHODS: The plasma levels of ascorbic acid,vitamin E and lipoperoxides in patients with liver cirrhosis were measured, and the results were compared with those of sex-and age-matched healthy subjects. RESULT: The plasma levels of ascorbic acid, vitamin E and lipoperoxides in the patients group were (42.94 +/-6.99)micromol/L, (17.99 +/-3.51)micromol/L and (14.09 +/-1.28)micromol/L, respectively, while those in the control group were (53.30 +/-9.45)micromol/L (t=9.50, P=0.000), (24.59 +/-7.22)micromol/L (t=7.94, P=0.000) and (12.11 +/-1.20)micromol/L (t=17.21, P=0.000), respectively. CONCLUSION: The levels of ascorbic acid and vitamin E in patients with liver cirrhosis decrease significantly,which may indicates the disturbance of balance between oxidation and antioxidation.

Detection of H.pylori DNA in gastric epithelial cells by in situ hybridization.

AIM: To investigate the presence of H.pylori DNA within gastric epithelial cells in patients with H.pylori infection and its possible carcinogenic mechanism. METHODS: Total 112 patients, with pathologically confirmed chronic superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, atypical hyperplasia or gastric cancer were studied. Among them, 28 were H.pylori negative and 84 H.pylori positive. H.pylori DNA in gastric epithelial cells was detected by GenPoint catalyzed signal amplification system for in situ hybridization. RESULTS: In the H.pylori positive group, zero out of 24 chronic superficial gastritis (0.0%), four out of 25 precancerous changes (16.0%) and thirteen out of 35 gastric cancers (37.1%) showed H.pylori DNA in the nucleus of gastric epithelial cells, the positive rates of H.pylori DNA in the nucleus of gastric epithelial cells were progressively increased in chronic superficial gastritis, precancerous changes and gastric cancer groups (chi(2)=12.56, P=0.002); One out of 24 chronic superficial gastritis (4.2%), eleven out of 25 precancerous changes (44.0%) and thirteen out of 35 gastric cancers (37.1%) showed H.pylori DNA in the cytoplasm of gastric epithelial cells (chi(2)=10.86, P=0.004). In the H.pylori negative group, only one patient with gastric cancer was found H.pylori DNA in the nucleus of gastric epithelial cells; Only two patients, one patient with precancerous changes and another with gastric cancer, showed H.pylori DNA in the cytoplasm of gastric epithelial cells. Furthermore, H.pylori DNA must have been in the cytoplasm as long as it existed in the nucleus of gastric epithelial cells. CONCLUSION: H.pylori DNA exists both in the nucleus and the cytoplasm of gastric epithelial cells in patients with H.pylori infections. The pathological progression from chronic superficial gastritis, precancerous changes to gastric cancer is associated with higher positive rates of H.pylori DNA presence in the nucleus of gastric epithelial cells.