Naloxone or Vagotomy Does Not Influence Centrally Octreotide-induced Inhibition of Gastric Acid Secretion in Rats

Summary： To investigate the effect of preceding naloxone injection into the third cerebroventricle or acute subdiaphragmatic vagotomy on the gastric acid secretion inhibited by the somatostatin analogue octreotide given by intracerebroventricular （icv） injection. The third ventricles were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later, acute gastric lumen perfusion was carried out. The gastric perfusion samples were collected every 10 min and were titrated by 0.01 mol/L NaOH to neuter. On the basis of subcutaneous injection of pentagastrin （G-5, 160 g/kg）, icv injection of physiological saline （group A, n=20）, icv injection of octreotide （0.05 μ g） （group B, n=20）, icv injection of naloxone （2.5 μ g）＋octreotide （0.05 μg） （group C, n=20）, acute subdiaphragmatic vagotomy＋ icv injection of physiological saline （group D, n=20）, or acute subdia- phragrnatic vagotomy＋icv injection of octreotide （0.05 μg） （group E, n=20） were conducted. Before and after icv injection, 1-h total acid output （TAO） was determined and compared. The experimental data were expressed in change rate （%） of TAO. The change rates （%） of TAO were 4.60 % in group A, -20.35 % in group B, - 18.06 % in group C, 5.01% in group D and -21.59 % in group E, respectively. Comparison of group B or C versus group A showed that P〈0.01 and comparison between the group E versus group D showed that P〈0.01. Whereas the differences between group C and group B, group E and group B were not statistically significant （P〉0.05 for all）. The results indicate that the central inhibition of gastric acid secretion by octreotide may not be mediated by the endogenous opi- ate substance or its receptor and the peripheral pathway for icv injection of octreotide to suppress gastric acid secretion is via extra-vagus route.

Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions

AIM To investigate the changes of gastric acidproduction and its mechanism in shock period ofsevere burn in rats.METHODS A rat model with 30% TBSA full-thickness burn injury was employed and thegastric acid production,together with gastricmucosal blood flow(GMBF)and energy charge(EC)were measured serially within 48hpostburn.RESULTS The gastric acid production in theacute shock period was markedly inhibited aftersevere burn injury.At the 3rd h postburn,thegastric juice volume,total acidity and acidoutput were already significantly decreased(P【0.01),and reached the lowest point,0.63mL/L±0.20mL/L,10.81mmol/L±2.58mmol/L and 2.23mmol/h±0.73mmol/hrespectively,at the 12th h postburn.Althoughrestored to some degree 24 h after thermalinjury,the variables above were stillstatistically lower,compared with those ofcontrol animals at the 48th h postburn.TheGMBF and EC were also significantly reducedafter severe burns,consistent with the trend ofgastric acid production changes.CONCLUSION Gastric acid production,as wellas GMBF and EC was predominantly decreased in the early postburn stage,suggesting that gastricmucosal ischemia and hypoxia with resultantdisturbance in energy metabolism,but notgastric acid proper,might be the decisive factorin the pathogenesis of AGML after thermalinjury,and that the preventive use of anti-aciddrugs during burn shock period wasunreasonable in some respects.Therefore,taking effective measures to improve gastricmucosal blood perfusion as early as possiblepostburn might be more preferable for the AGMLprevention and treatment.

No relationship between IL-1B gene polymorphism and gastric acid secretion in younger healthy volunteers

AIM: To investigate the influence of IL-1B-511 gene polymorphism on IL-1B mRNA expression and gastric acid output in individual with or without Helicobacter pylori (H pylori) infection.METHODS: IL-1B mRNA expression and gastric acid secretion in 117 health volunteers were assayed using semi-quantitative RT-PCR and gastric juice assay, respectively. Pepsinogen (PG) Ⅰ and Ⅱ of 255 subjects (including 117 health volunteers) were also examined.RESULTS: T/T genotype individuals with H pylori infection had a more decreased PG Ⅰ/Ⅱ ratio. In gastric antrum mucosa, the individuals with H pylori infection had higher IL-1B expression than those without H pylori infection, but there was no obvious difference among each genotype. In gastric corpus, the individuals with H pylori infection had a significantly higher IL-1B expression than those without H pylori infection. IL-1B-511T/T genotype was markedly higher as compared with the other two genotypes. Both maximal acid output and basic acid output were similar among each genotype in IL-1B-511 gene locus, regardless of H pylori infection.CONCLUSION: IL-1B-511 T allele does not decrease gastric acid output, although it has a stimulated influence on IL-1B expression. Consequently, the pathway,through which IL-1B plays a central role in gastric cancer development, might not depend on low acid, but on the other regulation mechanisms.

Effect of somatostatin analogue octreotide injected into the third cerebral ventricle on pentagastrin-induced gastric acid secretion in rats

AIM： To investigate the effect of long-lasting somatostatin analogue octreotide （Oct） injected into the third cerebral ventricle （TCV） on gastric acid secretion in rats. METHODS： TCVs were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later acute gastric lumen perfusion was carried out and gastric acid was continuously washed with 37℃ saline by a perfusion pump. Gastric perfusion samples were collected every 10 min and titrated by 0.01 moL/L NaOH to neutral. On the basis of subcutaneous （sc） injection of pentagastrin （G-5, 160 μg/kg）, Oct （0.025 μg, 0.05 μg, 0.1 μg, n=12 in each group） or vehicle （pyrogen-free physiological saline, n = 10） was injected into the TCV, Before and after the TCV injection, 1 h total acid output （TAO） was determined and experimental data were expressed in change rate （%） of TAO. RESULTS： Oct （0.025, 0.05 and 0.1 μg） injected into the TCV resulted in change rate of 1.56% （P〉0.05）, 20.21% （P〈 0.01） and 37.82% of TAO （P〈 0.001）, respectively. Moreover, comparison in change rate of TAO among these 3 doses showed P〈 0.05 between 0.025μg and 0.05 μg, P〈 0.01 between 0.025 μg and 0.ling, and P〈 0.05 between 0.05μg and 0.1 μg. However, sc injection of 0.05 μg Oct had no effect on G-5 stimulated gastric acid secretion. CONCLUSION： Octreotide injected into the third cerebral ventricle inhibits gastrin-induced gastric acid secretion in a dose-dependent manner.

Gastric acid level of humans must decrease in the future

Proton pump inhibitors strongly inhibit gastric acid production,but digestion problems do not generally arise.We can intake almost ordinary food even after total gastrectomy.Small intestine itself can digest and absorb food using various digestive enzymes without digestion in the stomach.The pH level of gastric acid in humans is much lower than that of most animals,and very close to that of carrion-eating animals called scavengers.It is assumed that ancient humans became bipedal approximately 4 million years ago.It was difficult for humans,who just started unstable bipedal locomotion,to catch quadrupedal-walking animals that can move faster,without special hunting tools.They may have eaten remaining carcasses,which is mainly the leftovers of carnivora species,as animalderived food.The benefit to produce a volume of gastric acid for humans is carrion eating,in which disinfection by gastric acid is important.Humans produce a high concentration of gastric acid to enable consumption of a diet containing some bacteria and support this lifestyle by consuming significant energy to protect themselves from gastric acid.Now,the opportunity for strong deleterious bacteria to enter the gastrointestinal tract has decreased because of the organized clean environment.If this hygienic environment is maintained for a long time,our gastric acid level must be decreased gradually.

Bravo capsule system optimizes intragastric pH monitoring over prolonged time:Effects of ghrelin on gastric acid and hormone secretion in the rat

AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days.For comparison,a gastric fistula model was used.Effects of ghrelin and esomeprazole,with or without pentagastrin,on gastric pH were studied.In addition,effects of esomeprazole on plasma ghrelin,gastrin and somatostatin were analyzed.RESULTS: All rats recovered after surgery.The average 24-h pH during free feeding was 2.3 ± 0.1 (n = 20) with a variation of 18% ± 6% over 5 d.Ghrelin,2400 pmol/kg,t.i.d.increased pH from 1.7 ± 0.1 to 3.1 ± 0.3 (P < 0.01) as recorded with the Bravo system.After esomeprazole (1 mg/kg,3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 ± 0.1,with day-to-day variation over the entire period of 8% ± 3%.The fistula and pH studies generated similar results.Acid inhibition with esomeprazole increased plasma ghrelin from 10 ± 2 pmol/L to 65 ± 26 pmol/L (P < 0.001),and somatostatin from 10 ± 2 pmol/L to 67 ± 18 pmol/L (P < 0.001).CONCLUSION: pH measurements with the Bravo capsule are reliable,and comparable to those of the gastric fistula model.The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short-and long-term evaluation of effects of drugs and hormones.

Influence of gastric inhibitory polypeptide on pentagastrinstimulated gastric acid secretion in patients with type 2 diabetes and healthy controls

AIM： Gastric inhibitory polypeptide is secreted from intestinal K-cells in response to nutrient ingestion and acts as an incretin hormone in human physiology. While animal experiments suggested a role for GIP as an inhibitor of gastric secretion, the GIP effects on gastric acid output in humans are still controversial. METHODS： Pentagastrin was administered at an infusion rate of 1 μg . kg^-1 . h^-1 over 300 min in 8 patients with type 2 diabetes （2 female, 6 male, 54± 10 years, BMI 30.5 ± 2.2 kg/m^2; no history of autonomic neuropathy） and 8 healthy subjects （2/6, 46 ± 6 years., 28.9 ± 5.3 kg/ m^2）. A hyperglycaemic clamp （140 mg/dl） was performed over 240 min. Placebo, GIP at a physiological dose （1 pmol . kg^-1 . min^-1）, and GIP at a pharmacological dose （4 mol . kg^-1 . min^-1） were administered over 60 min each. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at the beginning of each infusion period, respectively. Gastric volume, acid and chloride output were analysed in 15-min intervals. Capillary and venous blood samples were drawn for the determination of glucose and total GIP. Statistics were carried out by repeated-measures ANOVA and one-way ANOVA. RESULTS： Plasma glucose concentrations during the hyperglycaemic clamp experiments were not different between patients with type 2 diabetes and controls. Steady-state GIP plasma levels were 61 ±8 and 79 ± 12 pmol/I during the low-dose and 327±35 and 327± 17 pmol/I during the high-dose infusion of GIP, in healthy control subjects and in patients with type 2 diabetes, respectively （P= 0.23 and p 0.99）. Pentagastrin markedly increased gastric acid and chloride secretion （P〈 0.001）. There were no significant differences in the rates of gastric acid or chloride output between the experimental periods with placebo or any dose of GIP. The temporal patterns of gastric acid and chloride secretion were similar in patients with type 2 diabetes and healthy controls （P= 0.86 and P= 0.61, respectively）. CONCLUSION： Pentagastrin-stimulated gastric acid secretion is similar in patients with type 2 diabetes and healthy controls. GIP administration does not influence gastric acid secretion at physiological or pharmacological plasma levels. Therefore, GIP appears to act as an incretin rather than as an enterogastrone in human physiology.

Effects of Supplemental Histamine on Gastric Acid Secretion, Digestive Enzyme Activities, Intestinal Microfloral of Early Weaned Piglets

Two experiments were conducted to study the effect of supplemental histamine in the diet of early-weaned piglets. In experiment A, 24 cross bred piglets with an average body weight of 6.10±0. 40 kg, weaned at the age of 28 days, were divided into four groups, fed with basal diet of low dietary copper without (control) or with supplemental histamine at 60, 120, 180μg kg-1 BW. During the two weeks and the third week after weaning, ADG(average daily gain) of piglets were increased by 15.8%(P<0. 05), 9.5%(P< 0.10) by addition of 60μg kg-1 BW histamine, but decreased by addition of 180μg kg-1BW histamine, which also increased the amount of E. coli in colon and the scour incidence. The secretion of gastric acid and pepsin were improved by both dose of supplemental histamine (60, 180μg kg-1BW) and gastric digesta pH were decreased by both. Addition of 60 μg kg-1 BW histamine improved the activities of trypsin, amylase in duodelum digesta. In experiment B, 12 cross bred piglets with an average body weight of 6. 85±0.35 kg, weaned at the age of 28 days, were divided into two groups, fed with basal diet of high dietary copper without (control) or with supplemental 60 μg kg-1 BW histamine. During the two weeks and the third week after weaning, ADG of piglets were increased by 9. 8% (P<0.05), 7. 0% (P<0. 10). The secretion of gastric acid, activities of trypsin and amylase in duodelum digesta, were also improved by addition of 60 μg kg-1BW histamine. The results showed that addition of histamine (60μg kg-1BW) in early weaned piglets could increase the secretion of gastric acid and pepsin, reduce gastric digesta pH and scour incidence, improve activities of trypsin, amylase in duodelum digesta, and the growing performance of early weaned piglets.

Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

Gastric acid plays an important role in digesting food （especially protein）, iron absorption, and destroying swallowed micro-organisms. H＋ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like （ECL） cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, longterm hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastdn levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concem, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and dinically in the regulation of gastric acid secretion.

Construction and Expression of Recombinant Ghrelin Plasmid and Effects on Growth Performance and Gastric Acid Secretion of Rats

The paper was to study construction and expression of rGhrelin （pcDNA3 -Ghrelin） and its effect on growth performance and gastric acid secretion of rats. Ghrelin amplified from gastric mucosa of weaned piglets was cloned into the expression vector pcDNA3 to get recombinant plasmid pcDNA3 - Ghrelin. Twelve weaning rats were randomly divided into two groups, six rats each group. The rats in each treatment group were individually injected with 100pg of naked plasmid pcDNA3 -Ghrelin, and the rats in control group were injected with empty plasmid. The weights and feed consumption of rats were measured after injection for 7, 14 and 29 d, respectively. The rats were sacrificed at the end of the experiment, and their stomach was separated and weighed, the pH value of gastric juice was measured as well. The results showed that the average daily gain of rats at 7 and 29 d were significantly higher than that in control group, respectively （P〈0.05）, and feed consumption did not have significant chan- ges; the feed meat ratio of rats in the treatment groups was significantly lower than that in control group （ P 〈0.05） ; the gastric relative weight and gastric weight did not change significantly, while the pH value of gastric juice of rats in treatment groups was significantly lower than that in control group （P 〈 0.05）. This indicated that after transfected expression of muscle tissue, ghrelin played an important regulatory role in growth and gastric acid secretion of rats.

Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?

AIM: To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients.

Gastric acid inhibitory and gastric protective effects of cannabis and cannabinoids

Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in ?9-tetrahydrocannabinol inhibit gastric acid secretion in humans and in experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2 deoxy-D-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.

Concomitant administration of gastric acid suppression might attenuates the clinical efficacy of gefitinib:a single cancer center retrospective study

Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.

Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett’s esophagus

Objective:To determine the characteristics of postprandial proximal gastric acid pockets(PPGAPs)and their association with gastroesophageal acid reflux in patients with Barrett’s esophagus(BE).Methods:Fifteen patients with BE(defined by columnar lined esophagus of≥1 cm)and 15 healthy individuals that were matched for age,gender,and body mass index,were recruited.The fasting intragastric p H and the appearance time,length,lowest p H,and mean p H of the PPGAP were determined using a single p H electrode pull-through experiment.For BE patients,a gastroesophageal reflux disease questionnaire(Gerd Q)was completed and esophageal 24-h p H monitoring was carried out.Results:The PPGAP was significantly longer(5(3,5)cm vs.2(1,2)cm)and the lowest p H(1.1(0.8,1.5)vs.1.6(1.4,1.9))was significantly lower in patients with short-segment BE than in healthy individuals.The PPGAP started to appear proximally from the gastroesophageal p H step-up point to the esophageal lumen.The acidity of the PPGAP was higher in the distal segment than in the proximal segment.In short-segment BE patients,there were significant correlations between the acidity and the appearance time and length of the PPGAP.The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes.The acidity of the PPGAP was associated with the De Meester scores,the Gerd Q scores,and the fasting intragastric p H.Conclusions:In patients with short-segment BE,a PPGAP is commonly seen.Its length and acidity of PPGAP are associated with gastroesophageal acid reflux,the De Meester score,and the Gerd Q score in patients with short-segment BE.

Gastric Mucosal Blood Flow and Acid Secretion in Rats

The relationship between gastric mucosal blood flow (GMBF) and gastric acid secretionwere studied in rats by using secretory stimulant (pentagastrin)and inhibitor(cimetidine). GMBFwas measured by Laser Doppler flowmetry (LDF) and gastric mucosal pH determined by microglasspH electrode. GMBF increased and gastric mucosal pH decreased significantly after intravenous injec-tion of 6μg/kg of pentagastrin; nevertheless GMBF decreased and gastric mucosal pH increasedmarkedly after intravenous administration of 100mg/kg of cimetidine. This indicates that pentagastrincan increase GMBF and gastric acid secretion, and cimetidine can decrease GMBF and gastric acidsecretion in rats, proving the close relationship between GMBF and gastric acid secretion in rats.

CHANGES OF GASTRIC ACID SECRETION AND SOMATOSTATIN AFTER ROUX-EN-Y CHOLANGIOJEJUNOSTOMY

The authors studied the changes of gastric acid secretion and determined the levels of somatostatin(SS) and gastrin (Gn)in blood, gastric jujce and

Peripheral mechanism of inhibitory effect of centrally administrated histamine on gastric acid secretion

AIM To study the peripheral mechanism of the inhibitory effect of intra third ventricular administration (icv) of histamine (HA) on gastric acid secretion in rats. METHODS Gastric acid was continuously washed with 37℃ saline by a perfusion pump in male adrenalectomized SD rats. Drugs were injected intravenously (iv) by a syringe pump and their effect on pentagastrin induced (10μg·kg·h, iv) gastric acid secretion was observed. RESULTS The inhibitory effect of HA (1μg, icv) on gastric acid secretion was blocked by subdiaphragmatic vagotomy, and pretreatment with atropine (0 005mg·kg·h, iv). Pretreatment with somatostatin antagonist, cyclo [7 aminoheptanoyl Phe D Trp Lys Thr(Bzl)], ( 2μg - 4μg ·kg· 100min , iv) could also block the inhibitory effect of HA on gastric acid secretion in a dose dependent manner. CONCLUSION The inhibitory effect of centrally administrated HA on gastric acid secretion may be mediated by vagi, acetylcholine M receptor and somatostatin.

Quality of healing of gastric ulcers: Natural products beyond acid suppression

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors(PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suf-fered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing(QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.

Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes(METCs)?Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU(G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase(G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells.CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.

Gastric juice acidity in upper gastrointestinal diseases

AIM: To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases. METHODS: Fasting gastric juice acidity of 165 healthysubjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination. RESULTS: Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively. CONCLUSION: Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice.