Curcumin attenuated paracetamol overdose induced hepatitis.

AIM: To investigate whether curcumin could attenuate hepatitis in mice with paracetamol overdose. METHODS: Male mice were divided into four groups. Group 1 (control, n = 8); was fed with distilled water; Group 2 [N-acetyl-P-aminophenol (APAP), n = 8]; was fed with a single dose of 400 mg/kg APAP dissolved in distilled water; Group 3 [APAP + curcumin (CUR) 200, n = 8], was fed with a single dose of 400 mg/kg APAP and 200 mg/kg CUR; Group 4 (APAP + CUR 600, n = 8), was fed with a single dose of 400 mg/kg APAP and 600 mg/kg CUR. Twenty-four hours later, the liver was removed to examine hepatic glutathione (GSH), hepatic malondialdehyde (MDA), and histopathologically. Then whole blood was withdrawn from heart to determine transaminase (serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase) and inflammatory cytokines [interleukin (IL)-12 and IL-18] levels by enzyme linked immunosorbent assay. RESULTS: Serum transaminase, hepatic MDA, and inflammatory cytokines increased significantly in the APAP compared with the control group. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups significantly decreased these parameters compared with the APAP group. The level of GSH decreased significantly in the APAP compared with the control group. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups significantly increased these parameters compared with the APAP group. The histological appearance of the liver in the control group showed normal. In the APAP-treated group, the liver showed extensive hemorrhagic hepatic necrosis at all zones. Curcumin supplementation in APAP + CUR 200 and APAP + CUR 600 groups, caused the liver histopathology to improve. In the APAP + CUR 200 group, the liver showed focal necrosis and but the normal architecture was well preserved in APAP + CUR 600 group. CONCLUSION: APAP overdose can cause liver injury. Results indicate that curcumin prevents APAP-induced hepatitis through the improvement of liver histopathology by decreased oxidative stress, reduced liver inflammation, and restoration of GSH.

Curcumin attenuates gastric cancer induced by N-methyl-N-nitrosourea and saturated sodium chloride in rats.

To determine effects of curcumin on N-methyl-N-nitrosourea (MNU) and saturated sodium chloride (s-NaCl)-induced gastric cancer in rats. Male Wistar rats were divided into 5 groups: control (CO), control supplemented with 200 mg/kg curcumin (CC), MNU + s-NaCl, MNU + s-NaCl supplemented with 200 mg/kg curcumin daily for the first 3 weeks (MNU + s-NaCl + C3W), and MNU + s-NaCl supplemented with curcumin for 20 weeks (MNU + s-NaCl + C20W). To induce stomach cancer, rats except for CO and CC were orally treated with 100 mg/kg MNU on day 0 and 14, and s-NaCl twice-a-week for the first 3 weeks. The experiment was finished and rats were sacrificed at the end of 20 weeks. Cancers were found in forestomachs of all rats in MNU + s-NaCl. The expressions of phosphorylated inhibitor kappaB alpha (phospho-IκBα), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and cyclin D1 significantly increased in MNU + s-NaCl compared with CO. Curcumin treatments for 3 and 20 weeks reduced the cancer incidence resulting in a decrease of phospho-IκBα expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin treatment for 20 weeks also decreased 8-OHdG expression in benign tumor-bearing rats compared with MNU + s-NaCl. Curcumin can attenuate cancer via a reduction of phospho-IκBα and 8-OHdG expressions, which may play a promising role in gastric carcinogenesis.

Lactobacillus plantarum B7 inhibits Helicobacter pylori growth and attenuates gastric inflammation.

AIM: To determine the anti-Helicobacter property of Lactobacillus plantarum B7 (L. plantarum) B7 supernatants in vitro and the protective effects of L. plantarum B7 on serum tumor necrosis factor-alpha (TNF-α), gastric malondialdehyde (MDA) level, apoptosis, and histopathology in Helicobacter pylori (H. pylori)-induced gastric inflammation in rats. METHODS: In vitro, the inhibition of H. pylori growth was examined using L. plantarum B7 supernatants at pH 4 and pH 7 and at the concentration of 1×, 5× and 10× on plates inoculated with H. pylori. The inhibitory effect of H. pylori was interpreted by the size of the inhibition zone. In vitro, male Sprague-Dawley rats were randomly divided into four groups including group 1 (control group), group 2 (H. pylori infected group), group 3 (H. pylori infected with L. plantarum B7 10(6) CFUs/mL treated group) and group 4 (H. pylori infected with L. plantarum B7 10(10) CFUs/mL treated group). One week after H. pylori inoculation, L. plantarum B7 10(6) CFUs/mL or 10(10) CFUs/mL were fed once daily to group 3 and group 4, respectively, for one week. Blood and gastric samples were collected at the end of the study. RESULTS: In vitro, at intact pH 4, mean inhibitory zone diameters of 8.5 mm and 13 mm were noted at concentrations of 5× and 10× of L. plantarum B7 supernatant disks, respectively. At adjusted pH 7, L. plantarum B7 supernatants at concentrations of 5× and 10× yielded mean inhibitory zone diameters of 6.5 mm and 11 mm, respectively. In the in vitro study, in group 2, stomach histopathology revealed mild to moderate H. pylori colonization and inflammation. The level of gastric MDA and epithelial cell apoptosis were significantly increased compared with group 1. The serum TNF-α level was significant decreased in group 3 compared with group 2 (P < 0.05). In addition, L. plantarum B7 treatments resulted in a significant improvement in stomach pathology, and decreased gastric MDA level and apoptotic epithelial cells. CONCLUSION: L. plantarum B7 supernatant inhibits H. pylori growth. This inhibition was dose-dependent and greater at pH 4. Moreover, L. plantarum B7 attenuated H. pylori-induced gastric inflammation.

Curcumin prevents indomethacin-induced gastropathy in rats.

AIM: To investigate the effects of curcumin on gastric microcirculation and inflammation in rats with indomethacin-induced gastric damage. METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group, n = 5) was fed with olive oil and 5% NaHCO(3) (-) (vehicle). Group 2 [indomethacin (IMN) group, n = 5] was fed with olive oil 30 min prior to indomethacin 150 mg/kg body weight (BW) dissolved in 5% NaHCO(3) (-) at time 0th and 4th h. Group 3 (IMN + Cur group, n = 4) was fed with curcumin 200 mg/kg BW dissolved in olive oil 0.5 mL, 30 min prior to indomethacin at 0th and 4th h. Leukocyte-endothelium interactions at postcapillary venules were recorded after acridine orange injection. Blood samples were determined for intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α levels using enzyme linked immunosorbent assay method. Finally, the stomach was removed for histopathological examination for gastric lesions and grading for neutrophil infiltration. RESULTS: In group 2, the leukocyte adherence in postcapillary venules was significantly increased compared to the control group (6.40 ± 2.30 cells/frame vs 1.20 ± 0.83 cells/frame, P = 0.001). Pretreatment with curcumin caused leukocyte adherence to postcapillary venule to decline (3.00 ± 0.81 cells/frame vs 6.40 ± 2.30 cells/frame, P = 0.027). The levels of ICAM-1 and TNF-α increased significantly in the indomethacin-treated group compared with the control group (1106.50 ± 504.22 pg/mL vs 336.93 ± 224.82 pg/mL, P = 0.011 and 230.92 ± 114.47 pg/mL vs 47.13 ± 65.59 pg/mL, P = 0.009 respectively). Pretreatment with curcumin significantly decreased the elevation of ICAM-1 and TNF-α levels compared to treatment with indomethacin alone (413.66 ± 147.74 pg/mL vs 1106.50 ± 504.22 pg/mL, P = 0.019 and 58.27 ± 67.74 pg/mL vs 230.92 ± 114.47 pg/mL, P = 0.013 respectively). The histological appearance of the stomach in the control group was normal. In the indomethacin-treated group, the stomachs showed a mild to moderate neutrophil infiltration score. Gastric lesions were erosive and ulcerative. In rats treated with indomethacin and curcumin, stomach histopathology improved and showed only a mild neutrophil infiltration score and fewer erosive lesions in the gastric mucosa. CONCLUSION: The results indicate that curcumin prevents indomethacin-induced gastropathy through the improvement of gastric microcirculation by attenuating the level of ICAM-1 and TNF-α.

An evaluation of a new in-house serum and urine ELISA test for detection of Helicobacter pylori infection in Thai population.

OBJECTIVE: Non-invasive tests play significant roles in the test-and-treat approach of Helicobacter pylori management. The detection of Helicobacter pylori antibodies in urine and serum is an easy and inexpensive way to diagnose this infection. In the present study, the authors developed an in-house serum and urine ELISA tests for H. pylori antibodies and evaluated their performance in a Thai population. MATERIAL AND METHOD: One hundred thirty eight dyspeptic patients were recruited. All subjects underwent upper endoscopy and one antral biopsy was obtained for rapid urease test, which was used as a standard reference. Urine and serum samples were collected before the procedure to run in-house ELISA test. RESULTS: Thirty (22%) subjects were positive for the rapid urease test and 108 (78%) were negative. Urine and serum optical density were significantly lower in the urease negative group (p = 0.011 and p < 0.001 respectively), while there were no differences in age, gender, or endoscopic findings between the two groups. Sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of urine and serum ELISA tests were 72% vs. 96.3%, 63.5% vs. 627%, 89.6% vs. 98.5%, 33.3% vs. 40.6%, and 64.5% vs. 69.8% respectively. CONCLUSION: In-house serum ELISA test for H. pylori antibodies yielded a very good sensitivity with acceptable specificity, whereas urine ELISA was unable to produce satisfactory sensitivity or specificity

Sequential therapy in clarithromycin-sensitive and -resistant Helicobacter pylori based on polymerase chain reaction molecular test.

BACKGROUND AND AIM: The present study was designed to determine the eradication rate of 10 day sequential therapy in genotypic clarithromycin-resistant Helicobacter pylori group identified by molecular polymerase chain reaction (PCR) detection in Thai patients. METHODS: Between May 2007 and June 2010, patients who had undergone gastroscopic examination at the King Chulalongkorn Memorial Hospital, for dyspeptic symptoms were recruited. Two biopsy samples from gastric antrum were obtained, one for rapid urease test and another for PCR. PCR-sequencing was performed to determine point mutations in 23S rRNA gene. Patients received 10 day sequential therapy consisting of lanzoprazole 30 mg and amoxicillin 1 g twice daily for 5 days followed by lanzoprazole 30 mg, clarithromycin 500 mg and nitroimidazole 500 mg twice daily for the remaining 5 days. Urea breath test (UBT) was performed to assess eradication therapy. RESULTS: A total of 151 patients (mean age 52.7 years, 75 males and 76 females) were recruited in this study. All patients completed sequential therapy without significant side effects. Point mutations at A2143G and A2142G were detected in 17 patients (11.3%). Overall eradication rate was 94%. The eradication rate in the group with point mutation was significantly lower than the eradication rate in the group without point mutation (64.7% vs 97.8%; odds ratio = 19.6 and 95% confidence interval = 4.3-88.8; P < 0.0001). CONCLUSION: Genotypic clarithromycin resistance was detected in only 11.3% of H. pylori infections in Thailand. Sequential therapy is highly effective in clarithromycin-sensitive but is less effective in clarithromycin-resistant H. pylori. PCR-molecular test could be a useful tool to identify antimicrobial resistance for optimizing an eradication regimen.

Curcumin suppresses gastric NF-kappaB activation and macromolecular leakage in Helicobacter pylori-infected rats.

AIM: To investigate whether curcumin could attenuate nuclear factor (NF)-kappaB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori (H. pylori)-infected rats. METHODS: Twenty-five male Sprague-Dawley rats were equally divided into five groups: control rats (Control), control rats supplemented with 600 mg/kg curcumin, H. pylori-infected rats (Hp), H. pylori-infected rats supplemented with 200 mg/kg curcumin (Hp + curI), and H. pylori-infected rats supplemented with 600 mg/kg curcumin (Hp + curII). In H. pylori-infected groups, rats were inoculated with H. pylori suspension twice a day at an interval of 4 h for 3 d. Two weeks later, 200 or 600 mg/kg curcumin was given once daily to curcumin-supplemented groups for 7 d. On the day of the experiment, macromolecular leakage in gastric mucosa was examined by intravital fluorescence microscopy. The stomach tissue was removed to examine NF-kappaB p65 expression in gastric epithelial cells by immunohistochemistry. RESULTS: The expression of NF-kappaB p65 in gastric epithelial cells and the macromolecular leakage from gastric mucosal microcirculation significantly increased in the Hp group compared with the Control group. The percentages of NF-kappaB p65 immunoreactive cells in Control and Hp groups were 10.72% +/- 2.10% vs 16.02% +/- 2.98%, P = 0.004, respectively. The percentages of macromolecular leakage in Control and Hp groups were 10.69% +/- 1.43% vs 15.41% +/- 2.83%, P = 0.001, respectively. Curcumin supplementation in Hp + curI and Hp + curII groups significantly decreased NF-kappaB p65 immunoreactive cells and macromolecular leakage compared with results in the Hp group. The percentages of NF-kappaB p65 immunoreactive cells in Hp + curI and Hp + curII groups were 11.79% +/- 2.13% (P = 0.017) and 11.42% +/- 1.68% (P = 0.010), respectively. The percentages of macromolecular leakage in Hp + curI and Hp + curII groups were 12.32% +/- 2.13% (P = 0.025) and 12.14% +/- 1.86% (P = 0.018), respectively. CONCLUSION: H. pylori-induced gastric inflammation in rats is associated with increased NF-kappaB activation and macromolecular leakage which can be reduced by curcumin supplementation.

Ten-day sequential therapy of Helicobacter pylori infection in Thailand.

OBJECTIVES: Antimicrobial resistance has decreased eradication rates of Helicobacter pylori worldwide. The objective of this study was to determine whether a sequential therapy regimen is effective in eradicating H. pylori in adults with nonulcer dyspepsia or peptic ulcer disease in Thailand. METHODS: A total of 115 patients with dyspepsia or peptic ulcer were enrolled in the study. (14)C-urea breath test, upper endoscopy, rapid urease test, bacterial culture, and antibiotic resistance assessment were conducted during the course of the treatment. In all, 115 patients underwent a 10-day sequential regimen, which consisted of lansoprazole (30 mg) plus amoxicillin (1 g) twice a day for 5 days, then lansoprazole (30 mg) with metronidazole (500 mg) twice a day, and clarithromycin (1,000 mg) once a day for another 5 consecutive days. Successful eradication was evaluated by negative urea breath test at least 4 weeks after stopping treatment. RESULTS: Successful eradication was achieved in 106 of 115 patients (95%). All patients completed the treatment, without any dropouts. Mild adverse effects included headache and palpitations. The prevalence rate of clarithromycin-resistant H. pylori was found to be 6.1%. CONCLUSIONS: The 10-day sequential treatment for H. pylori is well tolerated and provides a high eradication rate. This regimen can overcome the emergence of antibiotic resistance and may have a role as a first-line treatment for H. pylori infection in Thailand.

Effect of rebamipide on gastric ulcer healing caused by Helicobacter pylori and/or NSAIDs or non NSAIDs-non H. pylori.

BACKGROUND: Rebamipide, a gastro-protective drug, acts on stimulation of prostaglandin and mucus glycoprotein synthesis, inhibition of reactive oxygen species, inflammatory cytokines, and neutrophils activation. OBJECTIVE: To investigate the effect of rebamipide (mucosta) on healing of gastric ulcer caused by various etiologies. MATERIAL AND METHOD: Thirty patients with gastric ulcer underwent gastric antral and body biopsies for histopathology. Group classifications depended on H. pylori status using CLO test, histology or urea breath test and history ofNSAIDs taking. All patients received rebamipide 100 mg, three times a day, for 8 weeks. The symptoms and adverse effects were assessed in 4 weeks and 8 weeks after prescription. At the end of the present study, an endoscopy was repeated to evaluate ulcer healing and biopsy for gastric inflammation grading. RESULTS: According to the ulcer cause, there were seven patients with H. pylori+ NSAIDs+, nine patients with H. pylori + NSAIDs-, three patients with H. pylori - NSAIDs +, and 11 patients with H. pylori - NSAIDs-. The ulcers were completely healed in most patients with a history of NSAIDs use. There was a significant improvement of symptom scores from baseline in all groups (5.9 vs. 0.6, p < 0.001). The improvement of gastric inflammation scores were favorable in NSAIDs users (2.38 vs. 1.75, p = 0.011). All patients were satisfied as there were few adverse effects. CONCLUSION: Rebamipide is effective and well tolerated for treatment of gastric ulcers especially those caused by NSAIDs, as it promotes the improvement of gastric inflammation scores, clinical symptoms, and ulcer healing.

Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats.

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-kappaB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-kappaB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARgamma protein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-kappaB activation.

N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis.

AIM: To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH). METHODS: Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n=8) was free accessed to regular dry rat chow (RC) for 6 wk. Group 2 (NASH, n=8) was fed with 100% fat diet for 6 wk. Group 3 (NASH+NAC(20), n=9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study. RESULTS: The levels of total glutathione (GSH) and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7+/-93.2 vs 1337.5+/-31.5 micromol/L and MDA; 209.9+/-43.9 vs 3.8+/-1.7 micromol/g protein, respectively, P<0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. NAC treatment improved the level of GSH (1394.8+/-81.2 micromol/L, P<0.05), it did not affect MDA (150.1+/-27.0 micromol/g protein), but led to a decrease in fat deposition and necroinflammation. CONCLUSION: NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.

Incidence of Helicobacter pylori recurrent infection and associated factors in Thailand.

OBJECTIVE: To determine the incidence of H. pylori recurrent infection after successful eradication in 4-year follow-up study, and to evaluate the influencing factors for re-infection. MATERIAL AND METHOD: Thirty-seven patients (age range 20-74 years; average 49.06 +/- 14.03 years) were recruited of which 64.9% were females. The H. pylori infection was proved to be successfully eradicated in all patients. Annually, urea breath test (UBT) was assessed to determine H. pylori status after eradication. Age, sex, eating habit, water drinking, number of children, and treatment regimens against H. pylori were recorded A breath test was also performed on the patient's spouse. RESULTS: The H. pylori recurrence occurred in 5/37 (13.51%) of patients observed There were two patients in the first year, one patient each in the second, third, and fourth year The cumulative re-infection rate was 5.41% at 1-year 8.11% at 2-year 10.81% at 3-year and 13.51% at 4-year H. pylori infection of spouse was also frequent (80%). Even if the spouse was infected, 88.89% of patients will remain uninfected after 4-years of H. pylori eradication. No influencing factor for infection recurrence was detected. CONCLUSIONS: The risk of re-infection after H. pylori eradication was low in Thai patients after 4-year follow up. Annual re-infection rate was 3.38%. No dependent factors were associated with a recurrence.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma.

AIM: To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS: Serum IL-18, IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS: Serum IL-18, IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (>= 10(5) pg/mL) had a poorer survival than those with low serum IL-18 levels (< 10(5) pg/mL) (4 and 11 mo, respectively, P = 0.015). Multivariate analyses showed that serum IL-18 level, but not IL-6 and IL-12 levels, was a significant and independent prognostic factor of survival. CONCLUSION: These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus, the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Effects of N-acetylcysteine on oxidative stress in rats with non-alcoholic steatohepatitis.

OBJECTIVE: Prove the attenuated effects of N-acetylcysteine (NAC) on oxidative stress in rats with nonalcoholic steatohepatitis (NASH). MATERIAL AND METHOD: Male Sprague-Dawley rats were randomly divided into five groups. Group I (normal control) was fed regular dry rat chow (RC) for 6 weeks. Group 2 (NASH) was fed 100% fat diet for 6 weeks. Group 3-5 were fed 100% fat diet for 6 weeks, and then switched to RC alone (NASH + diet ; group 3), to RC + 20 mg/kg/day of NAC orally (NASH + diet + NAC20; group 4) or to RC + 500 mg/kg/day of NAC orally (NASH + diet + NAC500; group 5) for 4 weeks, respectively. They were sacrificed to collect blood and liver samples at the end of the present study. RESULTS: Levels of total glutathione (GSH), serum cholesterol, and hepatic malondialdehyde (MDA) were increased significantly in the NASH group compared with normal control. Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. Treatment with diet or diet plus NAC reduced the levels of GSH, cholesterol, and hepatic MDA back to normal. Liver sections from group 3-5 showed a decrease in fat deposition and necroinflammation in hepatocytes. However, no differences on all variables existed between diet alone and diet plus NAC groups. CONCLUSION: Our data indicate that diet or diet plus NAC treatment could attenuate oxidative stress and improve liver histopathology of NASH. However the addition of NAC is not better than diet treatment alone.

Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats.

This research was aimed to investigate anti-inflammatory effects of Aloe vera on leukocyte-endothelium in the gastric microcirculation of Helicobacter pylori (H. pylori)-infected rats. Thirty-six male Sprague-Dawley rats were divided into 3 groups: control, H. pylori-infected, and A. vera-treated group (200 mg/kg b.w., twice daily). H. pylori-inoculation was induced in the rats by the administration of H. pylori solution. Intravital fluorescence videomicroscopy was used to examine leukocyte adhesion in postcapillary venules on the posterior surface of stomach area on different periods after administration of A. vera. Serum tumor necrosis factor-alpha (TNF-alpha) level was measured in blood collected at the end of experiment by using ELISA technique. The results showed that in H. pylori-infected group on day 8, the leukocyte adhesion was 13.40+/-1.00 cells/100 microm vessel length and the TNF-alpha was 76.76+/-23.18 pg/ml, which increased significantly (p < 0.05), compared with the control group (leukocyte adhesion(control) = 2.54+/-0.6 cells/100 microm vessel length and TNF-alpha(control) = 9.92+/-2.62 pg/ml). Treatment with A. vera reduced the leukocyte adhesion (5.5+/-0.5 cells/100 microm vessel length), and TNF-alpha (26.31+/-6.38 pg/ml) significantly (p < 0.05). In conclusion, H. pylori enhanced leukocyte-endothelium interaction in the posterior stomach area markedly. This enhancement in leukocyte-endothelium interaction could be improved by the treatment of A. vera, associated with reduction in TNF-alpha level.

Diagnostic role of serum interleukin-18 in gastric cancer patients.

AIM: To determine the current status in various aspects of gastric cancer patients and to find out the clinical correlation with prognostic role of serum interleukins in Thai patients. METHODS: Sixty-eight patients were enrolled in this study at King Chulalongkorn Memorial Hospital during April 2003 to May 2005. Gastric cancer was histologically proven in 51 patients and gastric ulcer in 17 patients. Serum IL-6, IL-10, IL-12, and IL-18 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were 26 males (55.32%) and 21 females (44.68%) with their age ranging from 33 to 85 years (mean age 64.49 +/- 13.83 years). The common presentations were weight loss (41.2%), dyspepsia (39.2%), and upper gastrointestinal bleeding (15.7%). A total of 35.3% gastric cancer patients and 6.3% of gastric ulcer patients were smokers (P = 0.029). Moreover, 32.4% of gastric cancer patients and 6.3% of gastric ulcer patients were alcoholic drinkers (P = 0.044). Lesion location was pyloric-antrum in 39.4%, gastric body in 39.4%, upper stomach in 12.2% and entire stomach in 6.1% of the patients. H pylori infection was detected in 44.4%. The poorly-differentiated adenocarcinoma was the most common pathologic finding (60.7%). Surgical treatment was performed in 44.1% patients (total gastrectomy in 5.9%, subtotal gastrectomy in 32.4% and palliative bypass surgery in 5.9%). Systemic chemotherapy was given as an adjuvant therapy in 8.8% patients. Carcinomatosis peritoneii were found in 18.8% patients. The mean survival time was 13.03 +/- 9.75 mo. The IL-18 level in gastric cancer patient group (58.54 +/- 43.96 pg/mL) was significantly higher than that in gastric ulcer patient group (30.84 +/- 11.18 pg/mL) (P = 0.0001) (95% CI was 42.20, 13.19). The cut point of IL-18 for diagnosis of gastric cancer was 40 pg/mL, the positive predictive value was 92.31%. The IL-6 level in gastric cancer patients with distant metastasis (20.21 +/- 9.37 pg/mL) was significantly higher than that in those with no metastasis (10.13 +/- 7.83 pg/mL) (P = 0.037) (95% CI was 19.51, 0.65). The role of IL-10 and IL-12 levels in gastric cancer patients was to provide data with no significant difference. CONCLUSION: These findings demonstrate that serum IL-6 and IL-18, but not IL-10 and IL-12 levels may be the useful biological markers of clinical correlation and prognostic factor in patients with gastric cancer. Moreover, IL-18 could serve as a diagnostic marker for gastric cancer with a high positive predictive value.

Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats.

AIM: To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS: Male Spraque-Dawley rats (n=48) were divided into four groups. Group1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-alpha and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS: On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05) increased in the ulcer groups when compared to the control group. The level of TNF-alpha was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-alpha had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-alpha were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-alpha level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION: Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-alpha level and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-alpha level, elevate IL-10 level and promote gastric ulcer healing.

Efficacy of clarithromycin-based triple therapy for treating Helicobacter pylori in Thai non-ulcer dyspeptic patients with clarithromycin-resistant strains.

BACKGROUND: Antibiotic resistance of H. pylori is problematic because it reduces the efficacy of eradication therapy. The objective of the present study was to assess the eradication rates of triple therapy against clarithromycin-sensitive and clarithromycin-resistant strains of H. pylori in Thai non-ulcer dyspeptic patients. MATERIAL AND METHOD: Patients who underwent upper gastrointestinal endoscopy at King Chulalongkorn Memorial Hospital between September 2002 and December 2003 were included. The patients who had positive urease test and culture were enrolled for antimicrobial resistance. Isolates were considered resistant when the MIC was more than 1 mcg/ml for clarithromycin. The patients received a combination of pantoprazole 40 mg BID, clarithromycin MR 1 gm OD, and amoxicillin 1 gm BID, for 7 days. Urea [14C] breath test was performed for evaluation of H. pylori eradication at least 1 month after treatment. RESULTS: Of the 470 patients, H. pylori were identified by positive rapid urease test in 282 patients (69.0%). Of these, cultures for H. pylori were achieved in 113 patients (54.6%) and E-tests for clarithromycin were successfully placed in 69 isolations. There were 29 males and 40 females, mean age was 38.7 +/- 13.3 years. Primary H. pylori resistance to clarithromycin was observed in 16 of 69 patients (23.2%). The eradication rates were 90.6% (48/53) and 56.3% (9/16) in patients with clarithromycin sensitive and clarithromycin resistant H. pylori strains, respectively (p = 0.002). CONCLUSION: The authors reported a high rate of clarithromycin resistant H.pylori isolates in Thailand. Pretreatment resistance to clarithromycin has a significant impact on treatment failure with clarithromycin-based regimen.

14-day quadruple therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure in Thailand.

BACKGROUND: A quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as a second line therapy after Helicobacter pylori treatment failure. OBJECTIVE: To evaluate the efficacy of 14-day ranitidine bismuth citrate (RBC) base quadruple therapy after H. pylori treatment failure in Thai patients. METHOD AND MATERIAL: Between June 2003-May 2005, thirty-four patients who were H. pylori positive after first line (Omeprazole, Amoxicillin, Clarithromycin or Metronidazole) treatment failure received 14-day quadruple therapy with RBC (400 mg bid), Rabeprazole (20 mg bid), Metronidazole (500 mg tid) and Tetracycline (500 mg qid). Four weeks after completion of treatment, eradication was confirmed with 14C-urea breath test. RESULTS: There were 18 males (52.9%) and 16 females (47.1%) with a mean age of 47.3 +/- 14.6 years. Four patients dropped out due to side effects. Per-protocol eradication rate was 86.7% and the intention-to-treat eradication rate was 76.5%. Adverse effects were found in 38.2% with a bitter taste, nausea, and dizziness. The mean age in the treatment failure group was younger than that in the successful group (35.3 +/- 13.9 vs 51.1 +/- 13.9 years, p = 0.046, 95%CI, 0.3-31.5%). The abdominal symptoms were improved after eradication (82.4%). CONCLUSION: The 14-day quadruple therapy with ranitidine bismuth citrate is effective and well tolerated for the patients who failed with the Helicobacterpylori treatment. The patients with older age may receive a more favorable outcome of the treatment.

Evaluation of Helicobacter pylori stool antigen test in Thai patients with upper gastrointestinal bleeding.

OBJECTIVE: Stool antigen test was evaluated in comparison with other diagnostic tests for the diagnosis of H. pylori infection in Thai patients presented with upper gastrointestinal bleeding. MATERIAL AND METHOD: Fifty-six patients were enrolled and fecal specimen was obtained from 34 patients. The presence of H. pylori was considered if the culture was positive or at lease two of the other diagnostic tests (urea breath test, serology, rapid urease test or histology) were positive. Stool antigen test was performed by using commercially available monoclonal enzyme immunoassay (Amplified IDEIA HpStAR, Dako, Denmark). RESULTS: Of the 56patients, 35 (62.5%0) were considered H. pylori infected, while in 34patients tested by stool antigen test, 22 (64.71%) were infected. The prevalence of H. pylori infection as determined by each test is considered low (47.06% from stool antigen test; 42.50%from UBT, 65.85%from serology; 51.78%0from RUT- and 46.34% from histology). The sensitivity/specificity/accuracy (%) of stool antigen test was 69.56/100/ 79.41 compared to 73.91/100/85 of UBT 79.17/52.94/68.29 of serology, 80/95.23/85.71 of RUT and 82.61/ 100/90.24 of histology, respectively. CONCLUSION: In summary, the results of this study reveal that the prevalence of H. pylori was relatively low in upper gastrointestinal bleeding patients. Yielding a low sensitivity and accuracy, the stool antigen test is therefore not reliable for the diagnosis of H. pylori infection in patients with upper gastrointestinal bleeding.