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The effects of irinotecan combined with 4-amion pyridine on the proliferation of human colorectal cancer cell

Chinese Journal of Digestion.2009;29(8):534-537. doi:10.3760/cma.j.issn.0254-1432.2009.08.009

Objective To investigate the effects and potential mechanism of irinotecan (CPT-11), an antitumor drug, on human colorectal cancer cell line HT-29 and its impact on 4-amion pyridine (4-AP), a kalium ion channel blocker. Methods The effects of CPT-11, 4-AP and combination of two drugs on proliferation and invasion of HT-29 cells were measured by MTT and Transwell assay respectively. The impact of CPT-11 or 4-AP on cell apoptosis was determined by flow cytometry with Annexin-V and PI staining. The current of ATP sensitive potassium ion (IKATP) was measured by patch clamp. Results The CPT-11 could inhibit proliferation of HT-29 cells at dose from 1.0 to 64.0 μg/ml in dose-and time-dependent manners. Whereas the above effect was enhanced when CPT-11 combined with 4-AP (1.0 mmol/L). The administration of CPT-11 (16.0 μg/ml) or 4-AP (1.0 mmol/L) significantly induced the cell apoptosis and inhibited the invasion of HT-29 cells, furthermore, these effects could be enhanced by combination of two drugs. And the different concentrations of CPT-11 reduced the IKATP of cell membrane in negative dose-dependent manner. Conclusions The effects of CPT-11 on HT-29 cells, such as reducing proliferation and invasion as well as inducing the apoptosis, can be enhanced by 4-AP, which may be related to inhibition of ATP-sensitive potassium channels.

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Variation of serum ghrelin and leptin in patients with functional dyspepsia

Ying CHEN ; Wentian LIU ; Weili FANG

Chinese Journal of Digestion.2009;29(8):521-524. doi:10.3760/cma.j.issn.0254-1432.2009.08.005

Objective To investigate the alteration of serum ghrelin and leptin in patients with functional dyspepsia (FD) and their clinical significance. Methods Sixty patients with FD [-30 patients with postprandial distress syndrome(PDS) and 30 patinets with epigastric pain syndrome(EPS)] were enrolled. Thirty healthy subjects were severed as controls. The serum ghrelin and leptin were measured by enzyme linked immunosorbent assay and radioimmunosorbent assay, respectively. Results The concentrations of serum ghrelin and leptin were both significantly lower in patients with FD than in controls (P<0.01). Meanwhile, the concentrations of serum ghrelin and leptin in PDS patients were significantly lower compared with controls (P<0.01) and EPS patients (P<0.01). There was no significant difference in levels of serum ghrelin and leptin between controls and EPS patients(P>0.05). Conclusions The alterations of serum ghrelin and leptin in PDS patients are responsible for their reduction in FD patients. The PDS may he associated with abnormalities in gastrointestinal motility. There is an interaction between serum ghrelin and leptin in development of FD. The detection of serum ghrelin or leptin is helpful in classification and treatment of FD.

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Application of self-made gastroscope outer casing in treatment of esophagogastric variceal bleeding

Zhiyin LI ; Zhonglue WANG ; Gang ZHOU ; Huilin SHEN ; Jumei MA

Chinese Journal of Digestion.2009;29(8):510-513. doi:10.3760/cma.j.issn.0254-1432.2009.08.002

Objective To estimate the success rate of emergency endoscopic treatment in patients with esophagogastric variceal bleeding using self-made gastroscope outer casing and to investigate bow to prevent complications. Methods A total of 11 patients with esophagogastric variceal bleeding underwent endoscopic treatment with self-made gastroscope outer casing, which consisted of a wire reinforced plastic casing (1.05 cm in inner diameter, 1.35 cm in outer diameter and 50 cm in length), a 3.8 cm×3.8 cm balloon fixed on the casing head and its cavity connected to the gas pipeline placed in casing tail, an anti-reflux pad in the insert entrance of the endoscope tail as well.as a flushing hole. The endoscopy was introduced to the esophagus or stomch together with outer casing to wash and pump the hematocele out from the side of flushing hole. In patients with hemorrhagic lesion in esophageal vein, the balloon was used to press bleeding vein and intravascular sclerotherapy was performed simutanously. In those with hemorrhagic lesion in gastric vein, the balloon was pressed on esophageal vein near to the cardia and intravascular sclerotherapy was performed. Results During the process of examination, the hemorrhagic lesion was fully exposed because of flushing, and bleeding was controlted in all patients after sclerotherapy. No complication such as aspiration or perforation was seen. Conclusions For emergency endoscopic treatment of esophagogastric variceal bleeding, gastroscope outer casing is helpful in removing intragastric hematocele and maintaining a clear field of vision. It can be effectively improving the efficacy of sclerot herapy.

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Expressions of tight junction proteins and interleukin-6 in mucosa of reflux esophagitis

Feiyue LI ; Yan LI

Chinese Journal of Digestion.2009;29(9):549-553. doi:10.3760/cma.j.issn.0254-1432.2009.09.010

Objective To investigate the distribution and expression of tight junction proteins (including elaudin 1, occludin,ZO-1 and JAM-1) in mucosa of rats with reflux esophagitis (RE), and its underline mechanism in pathogenesis of RE. Methods Two hundred and twenty 8-week-old male Wistar rats were divided into sham operation control group (n=10), acid reflux group (n=70), alkaline reflux group (n=70) and mixed reflux group (n=70). The rats were sacrificed at day 3, 6, 9 and 14 after operation. The successful rate of modeling was assessed by evidence of inflammation in middle and low esophagus. Transmission electron microscopy (TEM) was used to observe the morphological changes of tight junction in esophageal epithelium. The mRNA and protein expressions of tight junction proteins were detected by Western blotting and RT-PCR, respectively. And interleukin (IL)-6 expression was measured by immunohistochemistry. Results At day 14 after the procedure, RE model was established in all executed rats. Successful rate of 100% was achieved. The microscopic observation showed that mucosa was damaged and thickened as the disease progressed. With TEM observation, widened intercellular space was noticed with fewer desmosomes. Elevated expressions of IL-6 and tight junction proteins were found in three model groups compared with control group. Whereas the expression of tight junction proteins in individual cells was gradually decreased with continuing hyperplasia in the basal layer. The mRNA and protein expressions of IL-6 and tight junction proteins were increased gradually as disease progressed. Conclusions The highly expression of tight junction proteins, which involves in the mechanism of RE by playing the role of positive regulation and synergism, may be early molecular event in development of RE. And IL-6 is an inflammatory factor in this process.

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Impact of CYP2C19 polymorphisms on eradication of Helicobacter pylori using triple therapy with esomeprazole

Lei ZHANG ; Jianming XU ; Qiao MEI ; Qiusen LI ; Yongmei HU

Chinese Journal of Digestion.2009;29(9):545-548. doi:10.3760/cma.j.issn.0254-1432.2009.09.009

Objective To prospectively compare the efficacy of omeprazole and esomeprazole on H. pylori eradication related to cytochrome P450 (CYP) 2C19 polymorphism in Chinese Han poputafion. Methods A total of 240 patients with peptic ulcer were randomly assigned to receive either EAC (amoxicillin, clarithromyein and esomeprazole) treatment or OAC (amoxicillin, clarithromycin and orneprazole) treatment for one week with 120 each. Then, the patients were sustained treated with esomeprazol or omeprazole for 3 weeks. The endoscopic evaluation was performed 2 weeks after treatment. At the end of the treatment, a carbon-13 (13C) urea breath test (13C-UBT) was performed to determine H. pylori status. Polymerase chain reaction and restriction fragment length polymorphism were used to detect CYP2C19 genotypes including extensive metabolizer (EM), poor metabolizer (PM), homozygous (homEM) and hetEM. Results Two hundred and twenty five of 240 patients completed the study. H. pylori eradication was 79.2% with OAC regimen and 88.3% with EAC regimen by intention to-treat (ITT) analyses without difference (P>0.05). Whereas H. pylori eradication was 87.20/00 with OAC regimen and 91.4% with EAC regimen by per-protocol (PP) analyses without difference (P>0. 05). However, both ITT and PP analysis showed that there was significant difference in H. pylori eradication between EAC regimen (91.9% and 97.1%) and OAC regimen (71.8% and 77.8%) in patients with homEM genotype (P= 0.037 and P=0.028). Two weeks after treatment, the percentage of ulcer healing was 79.2% or 81.9% in EAC group and 69.2% or 76.1% in OAC group by ITT or PP analysis, respectively (P> 0.05). Low side effects were noted in EAC or OAC groups (3.3% vs. 7.5%,P>0.05). Conclusion The high eradication will be achieved by esomeprazole-based triple regimen which is superior to omeprazole-based triple regimen in treatment of patients with homEM genotype.

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Meta-analysis of proton pump inhibitor for preventing recurrence of non-steroidal anti-inflammatory drags-induced ulcers

Ying ZHANG ; Shiyao CHEN ; Jianfeng YAO ; Lijun WU ; Jian ZOU ; Xiaofeng YU

Chinese Journal of Digestion.2009;29(7):471-475. doi:10.3760/cma.j.issn.0254-1432.2009.07.010

Objective To assess the clinical efficacy and safety of proton pump inhibitors (PPI)for preventing recurrence of non-steroidal anti-inflammatory drugs (NSAIDs)-indueed upper gastrointestinal ulcers using meta-analysis. Methods Mono- or multicenter randomized controlled clinical trials related to NSAIDs-indueed ulcers were retrieved from database of China Biological Medicine and Medline from 1966 to 2007. The data were analyzed by RevMan 4. 2 software using random or fixed effects model. Results Ten randomized controlled trials including 3361 patients were included, The recta-analysis revealed that PPI treatment significantly reduced the recurrent rate of NSAIDs-associated ulcers (8. 7%) in comparison with controls (17. 2%, P = 0. 03). Those who received esomeprazole (4. 4%) or lansoprazole (18. 0%) had a low recurrence of peptic ulcers compared with controls (14.7% or 28.7%, P value= 0.01 or 0.05). But there was no significant differencebetween omeprazole and controls (P= 0. 16). The recurrence of NSAIDs-associated ulcers in patients treated with esomeprazole 20 mg or 40 mg and tansoprazole 15 mg were 4.4%, 4.3% and 19.7 % respectively. The stratify analysis showed that PPI therapy could effectively reduce recurrentce of non-selective NSAIDs-induced ulcer (P= 0. 009), but failed to selective cyclooxygenase (COX)-2 inhibitor induced ulcer. No severe adverse reactions were found in PPI groups. Conclusion PPI is effective and safe in prevention of NSAIDs-related ulcers without discontinuation of NSAIDs.

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Treatment of gastroesophageal reflux disease with esomeprazole: A long-term follow-up study

Yihong FAN ; Bin Lü ; Gaosong ZHANG ; Man JIN

Chinese Journal of Digestion.2009;29(7):468-470. doi:10.3760/cma.j.issn.0254-1432.2009.07.009

Objective To assess the efficacy and safety of esomeprazole in long-term or intermittent treatment of gastroesophageal reflux disease (GERD). Methods Twenty-eight patients with GERD who accepted esomeprazole 20 mg bid for 2 weeks were further divided into long-term treatment group and intermittent treatment group according to the protocol of therapy. Patients in long-term treatment group were received minimum dose that was needed to relief the symptoms for more than 6 months, whereas those in intermittent treatment group were received esomeprazole 20 mg qd until the symptoms completely disappeared, if symptoms relapsed the patients were treated again.The dosage, recurrence of symptoms and the side effects were compared between two groups. ResultsThirteen patients in long-term treatment group were treated for 7-44 months (20 mg daily in 7,twice daily in 5 and every other day in 1). While 15 patients in intermittent treatment group had a good relief of the symptoms. No adverse reactions was found in two groups. The follow-up study of 10-57 months in intermittent treatment group revcaled that the longer the treatment maintained,the longer the symptoms relieved (r=0. 447, P= 0. 008). Conclusion It is safe for esomeprazole in relieving symptoms of patients with GERD by long time or intermittent use.

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Clinical value of endoscopic placement of nasojejunal feeding tube for nutritional support in patients with severe acute pancreatitis

Feng JI ; Chunhua JIAO ; Yuyao HU ; Qinwei XU ; Jin ZHAO ; Weixing CHEN

Chinese Journal of Digestion.2009;29(7):446-450. doi:10.3760/cma.j.issn.0254-1432.2009.07.004

Objective To evaluate the clinical value of endoscopically nasojejunal feeding tube placement (ENFTP) for nutritional support in patients with severe acute pancreatitis (SAP). Methods Those SAP patients who treated with ENFTP (n= 47) or with total parenteral nutrition (TPN) (n=50) were retrospectively analyzed for laboratory parameters before and 1,2 and 4 weeks after nutrition support. Outcomes in the two groups were compared with respect to complications,mortality, duration of feeding, feeding costs,mechanical ventilation time and length of ICU or hospital stay. Results Four weeks after nutrition sypport, the hemoglobin and albumin were increased in ENFTP group as compared to TPN groups (P < 0. 05), while the blood sugar was decreased significant in ENFTP group than in TPN group (P<0.05). The incidence of peripancreatic or biliary infection and catheter-related infection were lower in ENFTP group than in TPN group. Duration of feeding and hospital stay were shorter, and nutrition cost was lower in ENFTP group (P<0.05). In addition, the APACHE Ⅱ score was significantly improved in ENFTP group(P<0.05). Conclusion ENFTP seems to be safe and less expensive in treatment of patients with acute pancreatitis.

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Effects of histone deacetylase 1 on proliferation and apoptosis of pancreatic cancer cell line

Daojian GAO ; Min XU ; Yuqi ZHANG ; Yiqi DU ; Jun GAO ; Yanfang GONG ; Hongyu WU ; Guoming XU ; Zhaoshen LI

Chinese Journal of Digestion.2009;29(8):525-528. doi:10.3760/cma.j.issn.0254-1432.2009.08.007

Objective To investigate effects of histone deacetylase 1 (HDAC1) gene silencing on proliferation and apoptosis of pancreatic cancer cell line PaTu8988. Methods The PaTu8988 cells were cultured and divided into control group (untreated), negative control group (treated with 30 nmol/L negative siRNA), low HDAC1 group (treated with 15 nmol/L HDAC1 siRNA) and high HDAC1 group (treated with 30 nmol/L HDAC1 siRNA). The real-time PCR and Western blot were used to detect the efficiency of HDAC1 gene silencing on mRNA and protein levels ,respectively, at 48 hours after transfection of HDAC1 siRNA. Cell proliferation and apoptosis were evaluated using cell counting kit and flow cytometry, respectively. Results Forty-eight hours after transfection of HDAC1 siRNA, the expression of HDAC1 mRNA level in PaTu8988 cells was 46.1%±6.1% in low HDAC1 group and 32.3%±1.4% in high HDACI group, which were lower than that in control group (100.0%±3.4%) and negative control group (87.4%±28.3%,P<0.05). The expression of HDAC1 protein was higher in control and negative control groups than in low and high HDAC1 groups. Cell survival rate was 100.0%±17.1% in control group, 87.1%±5.0% in negative control group, 68.7%±4.7% in low HDAC1 group and 61.6%±2.0% in high HDAC1 group with significant difference (P<0.05). Meanwhile, the cell apoptic rate in control (4.20%±0.95%) and negative control (4.59%±1.26%) groups was lower than that in low (10.09%±1.36%) and high (11.19%±6.07%) HDACI groups (P<0.05). Conclusions HDACI siRNA can effectively and specifically inhibit the expression of HDAC1 and proliferation of PaTu8988 cells and induce cell apoptosis.

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The clinical significance of two fecal occult blood tests in diagnosis of gastrointestinal hemorrhage

Ping GAO ; Shaogang ZHANG ; Meiyan ZHANG ; Zhuobin TANG ; Limei ZHANG ; Biao LU ; Lihong CHEN

Chinese Journal of Digestion.2009;29(8):518-520. doi:10.3760/cma.j.issn.0254-1432.2009.08.004

Objective To assess and compare chemical and immunochemical fecal occult blood tests (FOBTs) in diagnosis of gastrointestinal hemorrhage and their clinical significance. Methods The FOBT was carried out in 4474 in-patients, out-patients or subjects who had annual physical examination using both hemoccult Ⅱ (CFOBT) and colloidal gold chromagraphy (IFOBT) methods.Those who was positive for FOBTs would be re-tested for 2 times and followed by gastroscopy and colonoscopy as well as other examinations in order to find the reason and location of gastrointestinal hemorrhage. Results FOBT was positive in 390 (8.22%) patients, of which 163 (41.8%) were detected by CFOBT, 100(25.6%) by IFOBT, and 127(32.6%) by both CFOBT and IFOBT. The clinical, endoscopic and other examinations revealed that upper and lower gastrointestinal bleeding were found in 235 (60.3%) and 136 (34.9%) patients, respectively. The detective rates of upper and lower gastrointestinal bleeding were 90.2% and 67.6% by CFOBT respectively, and 42.5% and 93.4% by IFOBT, respectively. The obvious gastrointestinal bleeding could be detected by both CFOBT and IFOBT. The diseases related to gastrointestinal bleeding involved acute gastric mucosal lesion, peptic ulcer, gastric cancer and colonic polyp,colorectal cancer and piles, etc. Conclusions It is demonstrated that FOBT is still important in screening and diagnosis of gastrointestinal hemorrhage.The CFOBT is superior to IFOBT in detecting upper gastrointestinal bleeding, whereas the IFOBT is superior to CFOBT in detecting lower gastrointestinal bleeding.

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