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1

Gastric antisecretory and antiulcer activity of bovine hemoglobin  

PubMed Central

AIM: To investigate gastric antisecretory and gastroprotective activity of bovine hemoglobin (B-Hb) in rats. METHODS: Adult Albino-Wistar rats were divided into groups of 6 animals each. B-Hb in doses of 100, 300 and 900 mg/kg body weight was tested for gastric acid secretion and antiulcer activity. Gastric secretions were measured 6 h after pylorus ligation in rats pretreated with B-Hb. The acidity was measured by titrating gastric contents against 0.01 mol/L NaOH to pH 7. Indomethacin ulcers were produced by oral administration of 30 mg/kg bw in the rats pretreated with B-Hb one hour before indomethacin. Six hours after indomethacin stomach removed and ulcer index was recorded. Ethanol ulcer were produced by 1 mL of ethanol in the rats pretreated with B-Hb 30 min before the ethanol. One hour after ethanol stomach were cut open to score ulcers. Histological examination and analysis of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), and myeloperoxidase (MPO) were carried in gastric tissue following ethanol administration. RESULTS: In control rats pylorus ligation for 6 h resulted in the accumulation of 8.1 ± 0.61 mL of gastric secretion. The treatment of the rats with 100, 300 and 900 mg/kg of B-Hb produced a significant decrease in the volume of gastric secretion 5.6 ± 0.63, 5.5 ± 0.75 and 4.7 ± 0.58 mL respectively as compared to the control group [analysis of variance (ANOVA) F = 4.77, P < 0.05]. The lesion area in the control group was found to be 22.4 ± 3.2 mm2 six hours after the administration of indomethacin. Treatment of rats with B-Hb at doses of 100 mg/kg (24.3 ± 3.29 mm2), 300 mg/kg (16.2 ± 1.45 mm2) and 900 mg/kg (12.6 ± 1.85 mm2) produced a dose dependent decreased the lesion scores (ANOVA F = 4.50, P < 0.05). The ulcer index following one hour after 1 mL ethanol was 7.1 ± 0.31. Pretreatment of rats with B-Hb at the doses of 100 mg/kg (2.5 ± 0.42), 300 mg/kg (2.1 ± 0.4) and 900 mg/kg (0.7 ± 0.21) significantly inhibited the formation of gastric lesions (ANOVA F = 63.26, P < 0.0001). Histological examination of gastric mucosa following ethanol showed significant lesions in the form of gastric pits with detachment of the surface epithelium; vacuolation of epithelial cells and elongation of microvessels. The changes were dose-dependently attenuated by B-Hb. The treatment of rats with ethanol significantly decreased the Alcian blue binding capacity of gastric wall mucus (480 ± 25.6 ?g Alcian blue/g of tissue) as compared to control rats (667 ± 25.8 ?g). Pretreatment of rats with B-Hb at the doses of 100 mg/kg (516 ± 31.6 ?g/g), 300 mg/kg (558 ± 28.8 ?g/g) and 900 mg/kg (654 ± 33.8 ?g/g) significantly attenuated ethanol induced depletion of gastric wall mucus (ANOVA F = 8.05, P < 0.005). A significant and dose dependent increase of gastric mucosal NP-SH (ANOVA F = 19.62, P < 0.001) and decrease in MPO activity (ANOVA F = 3.1, P < 0.05) was observed in B-Hb treated rats. CONCLUSION: B-Hb possesses significant gastric antisecretory and gastroprotective activity against experimentally induced gastric lesion. The gastroprotective effects of B-Hb are accompanied by inhibition of neutrophils activity, reduction of oxidative stress and maintenance of mucosal integrity.

Al Asmari, Abdulrahman K; Al Omani, Saud; Elfaki, Ibrahim; Tariq, Mohammad; Al Malki, Ahmed; Al Asmary, Saeed

2013-01-01

2

Structural modification of H/sub 2/-receptor antagonists provide post-H/sub 2/-receptor gastric antisecretory activity  

SciTech Connect

In the course of investigations into the gastric antisecretory activity of potential H/sub 2/-receptor antagonists, examples were discovered in which structural modification of the molecule altered a) antisecretory activity in the pylorus-ligated rat and b) the response to various stimulants of (/sup 14/C)aminopyrine (AP) uptake in isolated rat gastric mucosal cell preparations. Wy-45,662 (N-(3-(3-(1-piperidinylmethyl)phenoxy)propyl)thieno(3,4-d) isothiazol-3-amine 1, 1-dioxide)), a very potent histamine H/sub 2/-antagonist and antisecretory agent in the rat (ED/sub 50/ (approx.) 0.3 mg/kg), had no effect in vitro at 1 ..mu..M on forskolin-induced (/sup 14/C)AP uptake while 10 nM Wy-45,662 completely suppressed histamine-stimulated (/sup 14/C)AP uptake. In contrast, the N-benzylated form of Wy-45,662, Wy-46,499 dose-dependently (10/sup -7/-10/sup -6/M) suppressed forskolin-stimulated (/sup 14/C)AP uptake while retaining modest antisecretory activity (ED/sub 50/approx.8 mg/kg) in vivo. Wy-46,499's modest antisecretory activity was thus attributable to inhibition via a post-histamine H/sub 2/-receptor mechanism.

Nielsen, S.T.; Dove, P.A.; Strike, D.P.; Schiehser, G.A.

1986-03-01

3

Chemical and physical properties of the human urinary glycoprotein with gastric antisecretory activity.  

PubMed Central

The chemical and physical properties of the high-molecular-weight glycoprotein (SO20, w = 8S; Ve=Vo on Sephadex G-200) with gastric antisecretory activity extracted from the urine of pregnant women were studied. Gel filtration in the presence of sodium dodecyl sulphate and sodium dodecyl sulphate/polyacrylamide-disc-gel electrophoresis indicated subunit mol.wts. of 16 000 +/- 1500 and 13 000 +/- 1000 respectively. Reaggregation of the subunits and partial recovery of the biological activity were observed on removal of the detergent. The partial C-terminal sequence was found to be Phe-Tyr-Leu-Val-OH, whereas glycine appears to be the N-terminal amino acid. The carbohydrate composition was examined; all galactosamine was found to be O-glycosidically linked to the polypeptide chain.

Lugaro, G; Pasta, P; Casellato, M M; Mazzola, G; Carrea, G

1976-01-01

4

Gastric antisecretory and antiulcer activities of an ethanolic extract of Bidens pilosa L. var. radiata Schult. Bip  

Microsoft Academic Search

Bidens pilosa var. radiata Schult. Bip. is used in folk medicine to treat stomach disorders including peptic ulcers. The ethanolic extract (0.5–2 g\\/kg) decreased the gastric juice volume, acid secretion, as well as pepsin secretion in pylorus ligated rats. B. pilosa extract showed antiulcer activity against indomethacin-induced gastric lesions. The extract effectively inhibited gastric haemorragic lesions induced by ethanol, and

A. Alvarez; F. Pomar; M. A. Sevilla; M. J. Montero

1999-01-01

5

Mechanism for gastric antisecretory effects of desmethylimipramine in rats.  

PubMed

The mechanism for the gastric antisecretory action of desmethylimipramine (DMI) was studied using the pylorus-ligated rat preparation. DMI was approximately 40 times more potent in decreasing gastric acid secretion when given into the lateral ventricles of the brain than when administered intravenously. The antisecretory effects of DMI could be blocked by the alpha 2-adrenoceptor antagonists yohimbine and SK&F 72223 and mimicked by central administration of an alpha 2-agonist. It could not be blocked by the alpha 1-antagonist prazosin or mimicked by alpha 1-adrenoceptor agonists. SK&F 72223 and yohimbine themselves produced small increases in gastric acid, but the increase output by SK&F 72223 failed to reduce the antisecretory response to atropine. Since DMI is not an alpha 2-adrenoceptor agonist, but is a potent inhibitor of norepinephrine uptake, these data suggest that the effects of DMI on gastric acid secretion are mediated indirectly via inhibition of catecholamine uptake at central synapses containing alpha 2-adrenoceptors. PMID:7318905

Pendleton, R G; McCafferty, J P; Roesler, J M; Hieble, J P

1981-11-01

6

Role of antisecretory agents for gastric endoscopic submucosal dissection.  

PubMed

Gastric endoscopic submucosal dissection (ESD) causes artificial gastric ulcers and there is no consensus regarding the optimal perioperative management in terms of prevention of intra- or postoperative bleeding and promotion of healing. Traditionally, 8-week administration of proton pump inhibitors (PPI) and mucosal protective agents were used in the same way as for peptic ulcer management. However, recent studies have revealed that prior use of PPI might reduce intraoperative bleeding or early-phase postoperative bleeding, and combination of histamine-2 receptor antagonist (H2RA), and second-look endoscopy might have a similar effect on postoperative bleeding to PPI. Additionally, the advantage of PPI over H2RA is not proven and the optimal duration of PPI may be shortened until 2 weeks when the deteriorating factors for ESD ulcer are excluded. Furthermore, mucosal protective agents may facilitate ulcer healing. Further studies are needed to determine the optimal treatment protocol before and after ESD for both prevention of bleeding complication and promotion of ulcer healing, by using available antisecretory agents and mucosal protective agents. PMID:23368844

Fujishiro, Mitsuhiro; Chiu, Philip W Y; Wang, Hsui-Po

2013-03-01

7

Evaluation of Anti-Secretory and Anti-Ulcerogenic Activities of Avipattikar Churna on The Peptic Ulcers in Experimental Rats  

PubMed Central

Background: Avipattikar churna, a poly-herbal formulation, is one of the popular ayurvedic formulations which is used for peptic ulcer diseases but the scientific documentation with regards to its effect for the indication is lacking. Aims: This study was carried out to evaluate the anti-secretory and the anti-ulcerogenic activities of the churna and to compare its activity with that of ranitidine in a pyloric ligated model of rats. Material and methods: Four groups of rats with 6 animals in each served as the ulcer controls, churna low dose (500 mg/kg), churna high dose (750mg/kg) and ranitidine (25mg/kg). The control group rats received only vehicle (2% (v/v) gum acacia), while the rats of the other groups received the respective dose of the churna or ranitidine which was suspended in the vehicle. The treatments were given twice a day, orally, for two days. After 1 hour of the last dose, pyloric ligations were performed and the rats were sacrificed for evaluation after four hours of the ligations. The gastric contents were collected and its volume, pH and acidity were measured. The numbers of ulcers and their lengths were measured which were used to calculate the gastric irritancy index and the curative ratio. The histological examinations of the gastric tissues were also performed. Results: The churna, in both doses, significantly decreased the volumes of the gastric contents, the ulcer score, the length of the ulcer, the gastric irritancy index and pH increased as compared to those in the control group. The effects of the churna were comparable to that of ranitidine. The histopathological evaluation of the gastric tissue also supported the results. Conclusion: Avipattikar churna has anti-secretory and anti-ulcerogenic effects which are comparable to those of ranitidine in peptic ulcer diseases.

Gyawali, Sudesh; Khan, Gulam Muhammad; Lamichane, Shreekrishna; Gautam, Jaya; Ghimire, Saurav; Adhikari, Rashmi; Lamsal, Reshma

2013-01-01

8

Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats.  

PubMed

In the present study, the gastroprotective mechanism of Xylocarpus granatum fruit and its active constituents gedunin and photogedunin was investigated. Chloroform fraction (Fr-CHCl(3)) of X. granatum fruit was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats and histamine (HA) induced duodenal ulcer model in guinea pigs. Potential anti-ulcer activity of Fr-CHCl(3) was observed against CRU (58.28%), AS (67.81%), AL (84.38%), PL (65.66%) and HA (61.93%) induced ulcer models. The standard drug omeprazole (10mg/kg, p.o.) showed 68.25% protection against CRU, 57.08% against AS and 69.42% against PL model and 70.79% against HA induced duodenal ulcer. Sucralfate, another standard drug (500 mg/kg, p.o.) showed 62.72% protection in AL induced ulcer model. Fr-CHCl(3) significantly reduced free acidity (51.42%), total acidity (30.76%) and upregulated mucin secretion by 58.37% respectively. Phytochemical investigations of Fr-CHCl(3) yielded gedunin (36%), photogedunin (2%). Further, Fr-CHCl(3) and its compounds gedunin and photogedunin significantly inhibited H(+) K(+)-ATPase activity in vitro with IC(50) of 89.37, 56.86 and 66.54 microg/ml respectively as compared to the IC(50) value of omeprazole (30.24 microg/ml) confirming their anti-secretory activity. Conclusively, Fr-CHCl(3) of Xylocarpus granatum was found to possess anti-ulcerogenic activity which might be due to its anti-secretory activity and subsequent strengthening of the defensive mechanism. This study is the first of its kind to show significant anti-secretory effect of gedunin and photogedunin. Therefore it could act as a potent therapeutic agent against peptic ulcer disease. PMID:19962286

Lakshmi, V; Singh, N; Shrivastva, S; Mishra, S K; Dharmani, P; Mishra, V; Palit, G

2010-07-01

9

Mechanism of gastric antisecretory effect of thiocyanate: further evidence for the thiocyanate-induced impediment in gastric H+,K+-ATPase function  

SciTech Connect

Two hypotheses have recently been proposed for the thiocyanate inhibition of gastric acid secretion--a protonophore mechanism and an uncoupling model. The mechanistic aspects for the latter scheme have been examined on the following basis: capability of generating verifiable predictions, supporting evidence that is unambiguous, and compatibility with experimental realities. Gastric microsomes bind 5 nmol of SCN-/mg, and a ''pure'' and highly active fraction of H+,K+-ATPase prepared from gastric microsomes binds about 15 nmol of SCN-/mg. The affinity of SCN- binding to gastric microsomes changes from 10 to 25 mM in the presence of 20 mM K+ suggesting competition between K+ and SCN-. Potassium also displaces the bound SCN- from ''pure'' H+,K+-ATPase with a Ki of about 25 mM. Of the cations tested--Tl+, K+, Rb+, Cs+, NH4+, Na+, and Li+--Tl+ was the most effective in displacing bound SCN- while Na+ and Li+ were without effect. The effects of anions such as Cl-, NO3-, and gluconate were found to be nonspecific and absolutely dependent on K+ as cocation. Sulfate and OCN- showed an ability to displace SCN- as both K+ and Na+ salts. For SO4(-2) the K+ form was much more effective than the Na+ salt. Besides these antagonistic effects of K+ and congeners with the H+,K+-ATPase-bound SCN-, a competition between K+ and SCN- was also observed at the level of gastric K+-stimulated pNPPase reaction. The effects of SCN- and two other unrelated anions, F- and NO2-, on artificial delta pH across the microsomal vesicles exhibited a lack of appreciable change up to 5 mM and a small (about 13%) reduction between 10 and 20 mM. A combination of CCCP and nigericin or valinomycin completely abolished the delta pH under identical conditions. The present data in conjunction with other reports suggest that the proton impediment model best explains the gastric antisecretory effects of SCN-.

Nandi, J.; Ray, T.K.

1986-02-01

10

Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea  

PubMed Central

Aim: The roots of the plant Aconitum heterophyllum (EAH) are traditionally used for curing hysteria, throat infection, dyspepsia, abdominal pain, diabetes, and diarrhea. Therefore, the present study was undertaken to determine the mechanism involved in the anti-diarrheal activity of roots of A. heterophyllum. Materials and Methods: Ant-diarrheal activity of ethanol extract at 50, 100, and 200 mg/kg p.o. was evaluated using fecal excretion and castor oil-induced diarrhea models, while optimized dose, that is, 100 mg/kg p.o. was further subjected to small intestinal transit, intestinal fluids accumulation, PGE2-induced enteropooling and gastric emptying test. To elucidate the probable mechanism, various biochemical parameters and Na+, K+ concentration in intestinal fluids were also determined. Further, antibacterial activity of extract along with its standardization using aconitine as a marker with the help of HPLC was carried out. Results: The results depicted a significant (P < 0.05) reduction in normal fecal output at 100 and 200 mg/kg p.o. of extract after 5th and 7th h of treatment. Castor oil-induced diarrhea model demonstrated a ceiling effect at 100 mg/kg p.o. with a protection of 60.185% from diarrhea. EAH at 100 mg/kg p.o. also showed significant activity in small intestinal transit, fluid accumulation, and PGE2-induced enteropooling models, which also restored the altered biochemical parameters and prevented Na+ and K+ loss. The extract with 0.0833% w/w of aconitine depicted a potential antibacterial activity of extract against microbes implicated in diarrhea. Conclusion: The study concluded antisecretory and antimotility effect of A. heterophyllum, which mediates through nitric oxide path way.

Prasad, Satyendra K.; Jain, Divya; Patel, Dinesh K.; Sahu, Alakh N.; Hemalatha, Siva

2014-01-01

11

Anti-secretory and cyto-protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers.  

PubMed

In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated. Chebulinic acid was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of chebulinic acid was observed against CRU (62.9%), AS (55.3%), AL (80.67%) and PL (66.63%) induced ulcer models. The reference drug omeprazole (10 mg/kg, p.o.) showed 77.73% protection against CRU, 58.30% against AS and 70.80% against PL model. Sucralfate, another reference drug (500 mg/kg, p.o.) showed 65.67% protection in AL induced ulcer model. Chebulinic acid significantly reduced free acidity (48.82%), total acidity (38.29%) and upregulated mucin secretion by 59.75% respectively. Further, chebulinic acid significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 65.01 ?g/ml as compared to the IC50 value of omeprazole (30.24 ?g/ml) confirming its anti-secretory activity. PMID:23462212

Mishra, Vaibhav; Agrawal, Manali; Onasanwo, Samuel Adetunji; Madhur, Gaurav; Rastogi, Preeti; Pandey, Haushila Prasad; Palit, Gautam; Narender, Tadigoppula

2013-04-15

12

Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers.  

PubMed

Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47?g/ml as compared to the IC50 value of omeprazole (30.24?g/ml) confirming its anti-secretory activity. PMID:23880327

Singh, Vinay Kumar; Mishra, Vaibhav; Tiwari, Sriniwas; Khaliq, Tanvir; Barthwal, Manoj Kumar; Pandey, Haushila Prasad; Palit, Gautam; Narender, Tadigoppula

2013-10-15

13

Antisecretory activity of plants used to treat gastrointestinal disorders in Mexico.  

PubMed

Aqueous and methanolic extracts from 26 medicinal plants used in Mexico to treat gastrointestinal disorders were screened to evaluate their antisecretory activity on cholera toxin-induced intestinal secretion in rat jejunal loops model. Extracts were tested at a dose of 300 mg/kg. From 56 samples tested, both extracts from Chiranthodendron pentadactylon, Hippocratea excelsa and Ocimum basilicum were the most potent with inhibition values ranging from 68.0 to 87.6%. On the other hand, the methanolic extract of Geranium mexicanum (aerial parts) and the aqueous extract of Bocconia frutescens showed the highest activity with inhibition values of 93.4 and 86.0%, respectively. The results obtained in this study give some scientific support to the use of the Mexican medicinal plants employed for the treatment of gastrointestinal disorders such as diarrhea. PMID:16174555

Velázquez, Claudia; Calzada, Fernando; Torres, Javier; González, Felipe; Ceballos, Guillermo

2006-01-01

14

Rocket "Eruca sativa": A salad herb with potential gastric anti-ulcer activity  

PubMed Central

AIM: To validate gastric anti-ulcer properties of Rocket “Eruca sativa” on experimentally-induced gastric secretion and ulceration in albino rats. METHODS: Gastric acid secretion studies were undertaken using pylorus-ligated rats. Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong alkalis, indomethacin and hypothermic restraint stress. The levels of gastric wall mucus (GWM), nonprotein sulfhydryls (NP-SH) and malondialdehyde (MDA) were also measured in the glandular stomach of rats following ethanol administration. The gastric tissue was also examined histologically. The extract was used in two doses (250 and 500 mg/kg body weight) in all experiments. RESULTS: In pylorus-ligated Shay rats, the ethanolic extract of Rocket “Eruca sativa L.” (EER) significantly and dose-dependently reduced the basal gastric acid secretion, titratable acidity and ruminal ulceration. Rocket extract significantly attenuated gastric ulceration induced by necrotizing agents (80% ethanol, 0.2 mol/L NaOH, 25% NaCl), indomethacin and hypothermic restraint stress. The anti-ulcer effect was further confirmed histologically. On the other hand, the extract significantly replenished GWM and NP-SH levels, as well as the MDA level significantly reduced by extract pretreatment. CONCLUSION: Rocket extract possesses anti-secretory, cytoprotective, and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect is possibly through prostaglandin-mediated activity and/or through its anti-secretory and antioxidant properties.

Alqasoumi, Saleh; Al-Sohaibani, Mohammed; Al-Howiriny, Tawfeq; Al-Yahya, Mohammed; Rafatullah, Syed

2009-01-01

15

Antisecretory drugs for diarrheal disease.  

PubMed

Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2-3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce faecal losses in patients with high-volume watery diarrhea has continued for more than 20 years. A variety of potential targets for antisecretory agents have been explored which include loci within the enterocyte (the chloride channel, calcium-calmodulin) and other sites such as enteric nerves and endogenous mediators (such as 5-HT, prostaglandins). Although the potential of calcium-calmodulin inhibition has as yet not been realised, preliminary studies suggest that there are chloride channel blockers under development that will find a place in the management of secretory diarrheas. Recent work has highlighted the importance of neurohumoral mechanisms in the pathogenesis of acute diarrhea. Potentiation of the effects of endogenous enkephalin activity by enkephalinase inhibition has already produced a safe, effective anti-secretory drug, racecadotril. Speculative early work indicates that there may be a role for antagonists of 5-HT, substance P, and VIP receptors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future. PMID:16699263

Farthing, Michael J G

2006-01-01

16

Gastric Antiulcerogenic and Hypokinetic Activities of Terminalia fagifolia Mart. & Zucc. (Combretaceae).  

PubMed

The acute toxicity, the antioxidant activity, and the pharmacological activity on the gastrointestinal tract of rodents of the ethanolic extract (TFEE) from the bark of Terminalia fagifolia Mart. & Zucc. (Combretaceae) and of its aqueous (TFAqF), hydroalcoholic (TFHAF), and hexanic (TFHEXF) partition fractions have been evaluated. TFEE presented low acute toxicity, antioxidant, and antiulcerogenic activity against ethanol-induced ulcers, which was partially blocked by pretreatment with L-NAME and indomethacin. It reduced the total acidity and raised the pH of gastric secretion. Additionally, TFEE delayed gastric emptying and slightly inhibited the small intestinal transit and also presented a weakly antidiarrheal activity. The antiulcerogenic and antioxidant activity were also detected in TFAqF and TFHAF but not in TFHEXF. The antisecretory and gastroprotective activity of TFEE partially involve the nitric oxide and prostaglandin participation. Nevertheless, TFEE, TFAqF, and TFHAF drastically reduced the mucus layer adhered to the gastric wall of rats treated with ethanol or indomethacin. Complementary studies are required in order to clarify the paradox of the presence of a gastroprotector activity in this plant that, at the same time, reduces the mucus layer adhered to the gastric wall. PMID:24900960

Nunes, Paulo Humberto M; Martins, Maria do Carmo C; Oliveira, Rita de Cássia M; Chaves, Mariana H; Sousa, Elcilene A; Leite, José Roberto S A; Véras, Leiz Maria; Almeida, Fernanda Regina C

2014-01-01

17

Gastric Antiulcerogenic and Hypokinetic Activities of Terminalia fagifolia Mart. & Zucc. (Combretaceae)  

PubMed Central

The acute toxicity, the antioxidant activity, and the pharmacological activity on the gastrointestinal tract of rodents of the ethanolic extract (TFEE) from the bark of Terminalia fagifolia Mart. & Zucc. (Combretaceae) and of its aqueous (TFAqF), hydroalcoholic (TFHAF), and hexanic (TFHEXF) partition fractions have been evaluated. TFEE presented low acute toxicity, antioxidant, and antiulcerogenic activity against ethanol-induced ulcers, which was partially blocked by pretreatment with L-NAME and indomethacin. It reduced the total acidity and raised the pH of gastric secretion. Additionally, TFEE delayed gastric emptying and slightly inhibited the small intestinal transit and also presented a weakly antidiarrheal activity. The antiulcerogenic and antioxidant activity were also detected in TFAqF and TFHAF but not in TFHEXF. The antisecretory and gastroprotective activity of TFEE partially involve the nitric oxide and prostaglandin participation. Nevertheless, TFEE, TFAqF, and TFHAF drastically reduced the mucus layer adhered to the gastric wall of rats treated with ethanol or indomethacin. Complementary studies are required in order to clarify the paradox of the presence of a gastroprotector activity in this plant that, at the same time, reduces the mucus layer adhered to the gastric wall.

Nunes, Paulo Humberto M.; Martins, Maria do Carmo C.; Oliveira, Rita de Cassia M.; Chaves, Mariana H.; Sousa, Elcilene A.; Leite, Jose Roberto S. A.; Veras, Leiz Maria; Almeida, Fernanda Regina C.

2014-01-01

18

Telomerase Activity in Gastric Cancer1  

Microsoft Academic Search

Although many genetic alterations have been reported in gastric can cer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immor tality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important

Eiso IIh am; Takashi Yokoyama; Naokuni Tatsumoto; Yuji Imamura; Yoshiaki Murakami; Takashi Kodama; Mieczyslaw A. Piatyszek; Jerry W. Shay; Yuichiro Matsuura

19

Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats.  

PubMed

Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague-Dawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50 mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12 mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages. PMID:22581435

Alirezaei, Masoud; Dezfoulian, Omid; Neamati, Shima; Rashidipour, Marzyeh; Tanideh, Nader; Kheradmand, Arash

2012-12-01

20

Antidiarrhoeal evaluation of rhizomes of Cryptocoryne spiralis Fisch. ex Wydler: antimotility and antisecretory effects.  

PubMed

The antidiarrhoeal activity of Cryptocoryne spiralis rhizomes extract (250, 500, 750 mg/kg, po) was evaluated using faecal excretion, castor oil-induced diarrhoea, small intestinal transit, intestinal fluid accumulation, gastric emptying and PGE2 induced enteropooling models in rats. In addition, various biochemical estimations, histopathological studies and antibacterial evaluations on strains responsible for diarrhoea were also performed. The results illustrated a significant reduction in normal faecal output rate after 5th and 7th h of treatment, while castor oil-induced diarrhoea model depicted a protection of 55.44% at same dose level from diarrhoea. The other models except, gastric emptying test demonstrated more pronounced effect at same dose level. A significant inhibition in nitric oxide, increase in carbohydrates, protein, DNA, Na(+) and K(+) level with minimum degeneration of colonic fibrous tissues and potent antibacterial activity were also observed. The antidiarrhoeal potential of C. spiralis may be as a result of antimotility and antisecretory type effect mediated through nitric oxide pathway. PMID:24597146

Prasad, Satyendra K; Laloo, Damiki; Kumar, Rajesh; Sahu, Alakh N; Hemalatha, S

2014-02-01

21

Antisecretory and antiulcer effect of the H2-receptor antagonist famotidine in the rat: comparison with ranitidine.  

PubMed Central

1 The effects of the new H2-receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally-induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound. 2 Both compounds inhibited acid secretion in a dose-dependent manner. Calculated ED50 values were 0.80 and 6.84 mg kg-1 for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs. 3 The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect. 4 Famotidine reduced, in a dose-dependent manner, ulcer incidence in stomachs of dimaprit-treated rats and in duodena of cysteamine-treated animals with a potency respectively 2 and 7 times higher than that of ranitidine. 5 Famotidine is therefore an effective antisecretory and untiulcer compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs.

Scarpignato, C.; Tramacere, R.; Zappia, L.

1987-01-01

22

Anti-secretory effects and pharmacokinetics of low dose ranitidine.  

PubMed

The purpose of this study was to examine the anti-secretory effect of low doses of orally administered ranitidine on meal-stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double-blind) in 15 healthy males (mean age 35 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4-h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (P < 0.01) decreased the peak and cumulative 4-h acid secretory responses to the first meal (range 58-93%), and the 60 and 80 mg doses significantly inhibited the response to the second meal by 31 and 43%, respectively. Total 8-h meal-stimulated acid outputs were decreased significantly in a dose-related manner (range 38-73%). Peak plasma ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t1/2 and clearances were independent of dose; however, AUC and Cmax were dose-related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (+/- 6.4) ng/ml. We conclude that modest doses (equivalent to 7-27% of the daily therapeutic dose) of ranitidine effectively suppress meal-stimulated gastric acid secretion in a dose-related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur. PMID:8218756

Koss, M A; Hogan, D L; Lane, J; Steinbach, J H; Isenberg, J I

1993-08-01

23

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats  

SciTech Connect

Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

Tariq, M.; Parmar, N.S.; Ageel, A.M.

1987-05-01

24

Magnetogastrographic detection of gastric electrical response activity in humans  

Microsoft Academic Search

The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is

Andrei Irimia; William O Richards; L Alan Bradshaw

2006-01-01

25

Gastric activity studies using a magnetic tracer.  

PubMed

A magnetic pulse generator has been set up in order to study gastric activity. Two coils 1.05 m in diameter, arranged in a Helmholtz configuration, were used. The system generated magnetic field pulses higher than 15 mT, of duration 17.3+/-1.2 ms. Measurements were performed in 11 male volunteers, with average age 29.3+/-6.4 years and body mass index 26.0+/-4.8 kg m(-2). Magnetite (Fe3O4) particles with diameters from 75 to 125 microm were used as magnetic tracers, which were mixed in 250 ml of yogurt in concentrations from 2 to 5 g. Signals were registered by using a high speed 3 axis fluxgate digital magnetometer and processed to determine the relaxation of the magnetic tracers by fitting a first-order exponential function to the data, a mean relaxation constant K = 116+/-40 s(-1) was obtained. Also, an average gastric peristaltic frequency was measured; a value of 3.2+/-0.3 cpm was determined. PMID:15535190

Cordova-Fraga, T; Bernal-Alvarado, J J; Gutierrez-Juarez, G; Sosa, M; Vargas-Luna, M

2004-10-01

26

Reserpine, vagal adrenergic activity and stress-induced acute gastric mucosal injury in the rat.  

PubMed Central

1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress-induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress-induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 +/- 2.7 mm2, mean +/- S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre-treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2-receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 +/- 3 mm2 and 27.5 +/- 2.3 mm2, respectively, mean +/- S.E., n = 10). Protection against the reserpine lesions by the alpha-adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P less than 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 +/- 3.4 mm2, mean +/- S.E., n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 +/- 4.5 mumol, mean +/- S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/- 2 mumol) or with atropine (19 +/- 1.8 mumol) or cimetidine (21 +/- 2 mumol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose-dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 +/- 4.1 mumol and 60.3 +/- 2.8 mumol vs. 61 +/- 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/- 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6

Salim, A S

1987-01-01

27

Antisecretory Action of the Extract of the Aerial Parts of Eremomastax speciosa (Acanthaceae) Occurs through Antihistaminic and Anticholinergic Pathways.  

PubMed

Objective. The objective of this study was to find out the possible antiulcer mechanism of action of Eremomastax speciosa. Method. Carbachol- and histamine-induced hypersecretion, associated with the pylorus ligation technique, were used in rats. Gastric mucosal ulceration, mucus production, pH, gastric volume, and acidity were measured. Results. Histamine and carbachol raised gastric acidity to 86.50 and 84.80?mEq/L, respectively, in the control rats, and the extracts (200?mg/kg) reduced gastric acidity to 34.60 and 39.00?mEq/L, respectively. Intraduodenal aqueous extract (400?mg/kg) in histamine- and carbachol-treated rats produced significant (P < 0.001) decreases in acid secretion to 28.50 and 28.80?mEq/L, respectively, and 100 percent inhibition of gastric ulceration. Augmented histamine-induced gastric acid secretion (90.20?mEq/L) was significantly reduced to 52.60 and 27.50?mEq/L by the 200 and 400?mg/kg doses of the aqueous extract, respectively. The extract significantly reduced (P < 0.001) the volume of gastric secretion and significantly increased mucus production. The ulcer inhibition potential of the extract significantly dropped to 25-44% (oral extract) and to 29-37% (duodenal extract) in carbachol/indomethacin-treated rats. Conclusion. The aqueous extract of E. speciosa has both cytoprotective and antisecretory effects. The antisecretory effect may involve a mechanism common to both cholinergic and histaminergic pathways. PMID:24695819

André Perfusion, Amang; Tan, Paul V; Ernestine, Nkwengoua; Barthélemy, Nyasse

2014-01-01

28

Changes in gastric myoelectric activity during space flight  

NASA Technical Reports Server (NTRS)

The purpose of the present study was to examine postprandial myoelectric activity of the stomach and gastric activity associated with space motion sickness using electrogastrography. Three crewmembers participated in this investigation. Preflight, subjects exhibited normal postprandial responses to the ingestion of a meal. Inflight, crewmembers exhibited an abnormal decrease in the power of the normal gastric slow wave after eating on flight day 1, but had a normal postprandial response by flight day 3. Prior to and during episodes of nausea and vomiting, the electrical activity of the stomach became dysrhythmic with 60-80% of the spectral power in the bradygastric and tachygastric frequency ranges. These findings indicate that gastric motility may be decreased during the first few days of space flight. In addition, changes in the frequency of the gastric slow wave associated with space motion sickness symptoms are consistent with those reported for laboratory-induced motion sickness.

Harm, Deborah L.; Sandoz, Gwenn R.; Stern, Robert M.

2002-01-01

29

Theoretical ellipsoidal model of gastric electrical control activity propagation.  

PubMed

A theoretical model of electric current propagation in the human stomach is developed using an approach in which the shape of the organ is assumed to be a truncated ellipsoid whose dimensions can be determined from anatomic measurements. The gastric electrical activity is simulated using a ring of isopotential electric current dipoles that are generated by a pacemaker situated in the gastric corpus. The dipoles propagate in the direction of the pylorus at a frequency of three cycles per minute. The advantages of employing ellipsoids in the analytical formulation of this gastric model are discussed in addition to the realism and usefulness of the approach. PMID:14682818

Irimia, Andrei; Bradshaw, L Alan

2003-11-01

30

Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats  

PubMed Central

Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action.

Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

2014-01-01

31

Biglycan enhances gastric cancer invasion by activating FAK signaling pathway  

PubMed Central

Biglycan (BGN) is an important member of small leucine-rich proteoglycans family, and has been implicated in oncogenesis and development of various human cancer types. Here we report that BGN promotes tumor invasion and metastasis of gastric cancer both in vitro and in vivo. BGN expression is significantly higher in gastric cancer tissues and associated with lymph node metastasis, depth of tumor invasion and TNM stage. BGN enhances gastric cancer cell wound healing, migration and invasion ability as well as the tube formation ability of endothelial cells in vitro. Animal experiments results in vivo are consistent with outcomes in vitro. BGN induces increased phosphorylation of FAK (Tyr576/577, Tyr925 and Tyr397) and Paxillin. These results indicate that BGN is upregulated, and plays an oncogenic role, in gastric cancer metastasis by activating the FAK signaling pathway.

Li, Jian-fang; Su, Li-ping; Yan, Min; Zhu, Zheng-gang; Liu, Bing-ya; Yang, Qiu-meng

2014-01-01

32

Gastric distention activates satiety circuitry in the human brain.  

PubMed

Gastric distention during meal ingestion activates vagal afferents, which send signals from the stomach to the brain and result in the perception of fullness and satiety. Distention is one of the mechanisms that modulates food intake. We measured regional brain activation during dynamic gastric balloon distention in 18 health subjects using functional magnetic resonance imaging and the blood oxygenation level-dependent (BOLD) responses. The BOLD signal was significantly changed by both inflow and outflow changes in the balloon's volume. For lower balloon volumes, water inflow was associated with activation of sensorimotor cortices and right insula. The larger volume condition additionally activated left posterior amygdala, left posterior insula and the left precuneus. The response in the left amygdala and insula was negatively associated with changes in self-reports of fullness and positively with changes in plasma ghrelin concentration, whereas those in the right amygdala and insula were negatively associated with the subject's body mass index. The widespread activation induced by gastric distention corroborates the influence of vagal afferents on cortical and subcortical brain activity. These findings provide evidence that the left amygdala and insula process interoceptive signals of fullness produced by gastric distention involved in the controls of food intake. PMID:18155924

Wang, Gene-Jack; Tomasi, Dardo; Backus, Walter; Wang, Ruiliang; Telang, Frank; Geliebter, Allan; Korner, Judith; Bauman, Angela; Fowler, Joanna S; Thanos, Panayotis K; Volkow, Nora D

2008-02-15

33

Seasonal variation in gastric myoelectrical activity in young Japanese females  

Microsoft Academic Search

In order to test our hypothesis that there is seasonal variation in digestion and absorption of dietary carbohydrate from the intestine, we previously determined the amount of unabsorbed carbohydrate after breakfast by the breath hydrogen test in the four seasons. In pursuing our hypothesis further, we also recorded gastric myoelectrical activity before and after the breakfasts. In the current report,

Yuki Tsumura; Naoko Hirota; Hiromi Tokura; Yoshiaki Sone

2007-01-01

34

Effect of Gastric Myoelectric Activity on Photoplethysmographic Signals  

Microsoft Academic Search

Understanding the hemodynamic interactions of a non-cardiac system with the main circulatory system is a challenging task in modern medicine. In this study the effect of gastric myoelectric activity (GMA) on peripheral blood volume pulse, acquired by photoplethysmographic (PPG) technique during fasting and postprandial states are analyzed using wavelets. PPG and Electrogastrogram (EGG) signals were acquired simultaneously from 8 healthy

S. Mohamed Yacin; M. Manivannan; V. Srinivasa Chakravarthy

35

The assay of pyruvate kinase activity in gastric mucosa.  

PubMed

Pyruvate kinase activity in gastric mucosal supernatant preparations shows large responses to exogenous effectors. At pH 7.5, fructose 1,6-diphosphate can cause large stimulations in activity. Alanine inhibits the reaction but this effect is partially reversed by fructose 1,6-diphosphate. In the absence of these compounds, 4.0-5.0 mM phosphoenolpyruvate (PEP) is required to generate maximal activity in the assay system used. Electrophoresis reveals an isoenzyme pattern containing only one form of pyruvate kinase, an M isoenzyme, in both fundic and antral mucosa. The pyruvate kinase of gastric mucosa thus resembles the M-type enzymes of leucocytes and liver. Measurements of activity at both 1.0 mM PEP and 4.0--5.0 mM PEP, with and without additions of fructose 1,6-diphosphate, are recommended for the reliable estimation of pyruvate kinase activity in this tissue. PMID:237638

Orwell, R L; Thornton, H C; Piper, D W

1975-05-01

36

Biomagnetic Techniques for Assessing Gastric and Small Bowel Electrical Activity  

NASA Astrophysics Data System (ADS)

Recent advances in electrophysiology of the gastrointestinal tract have emphasized the need for methods of noninvasive assessment of gastric and small intestinal electrical activity (GEA and IEA). While the cutaneous electrogastrogram (EGG) may reveal the frequency dynamics of gastric electrical activity, other parameters important for characterizing the propagating electrical activity are not available from EGG recordings. Recent studies on the electroenterogram (EENG) are promising, but low-conductivity abdominal layers have complicated the identification of small intestinal electrical rhythms in cutaneous recordings. The magnetogastrogram (MGG) and magnetoenterogram (MENG) are able to characterize gastric and intestinal electrical activity noninvasively in terms of its frequency, power and characteristics of its propagation. Superconducting QUantum Interference Device (SQUID) magnetometers are used to detect the minute magnetic fields associated with electrical activity of the gastrointestinal syncytium formed by interstitial cells of Cajal and smooth muscle networks. Changes in GEA and IEA that occur in response to disease or abnormal conditions are reflected in MGG and MENG signals. Magnetic methods for assessing the electrical activity of the stomach and small bowel thus show great clinical promise.

Bradshaw, L. Alan

2004-09-01

37

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans  

Microsoft Academic Search

The relationship of gastric motor activity and gastric emptying of 0.7mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (kg) with large inter-individual differences and large variability in

Kazutaka Higaki; Sally Y. Choe; Raimar Löbenberg; Lynda S. Welage; Gordon L. Amidon

2008-01-01

38

Antisecretory effect of prescribed appetite stimulator drug cyproheptadine in rat intestine.  

PubMed

Cyproheptadine (Cph) is an antiserotoninergic and antihistaminergic agent with alpha-blocking activity and central sedative effect. Cph has been found to be effective in stimulating appetite, but to our knowledge, its direct effects on the intestine have not been documented. We aimed to assess the antisecretory effects of Cph in rat proximal colon using Ussing chambers' technique. In basal and serotonin (5-HT)-stimulated conditions, Cph induced a dose-dependent reduction in short-circuit current (Isc). This effect was different in fed vs. fasted rats (EC50  = 1.9 × 10(-5 ) m and 4.9 × 10(-5 ) m, respectively). As expected, Cph induced a marked dose-dependent rightward shift of the concentration-response curve to 5-HT (pA2  = 5.4). The effect of Cph was found to be close to that of antisecretory agents in the following sequence: peptide YY > somatostatin > clonidine > Cph > C7-sorbin. To our knowledge, this is the first demonstration that Cph has a direct effect on the inhibition of electrogenic ionic secretion in intestinal epithelium in vitro. Our results indicate that Cph can modulate the intestinal transport of electrolytes and provide a new insight into the peripheral effects of this drug, which is frequently prescribed as appetite stimulator in developing countries. PMID:23565811

Meddah, Bouchra; Limas-Nzouzi, Nicolas; Mamadou, Godefroy; Miantezila, Joe; Soudy, Imar Djibrine; Eto, Bruno

2014-06-01

39

Normal gastric antral myoelectrical activity in early onset anorexia nervosa.  

PubMed Central

Anorexia, epigastric discomfort, nausea, and vomiting may result from disordered gastric motility and emptying. These features have been found in many adults with anorexia nervosa, but have never been investigated in early onset anorexia nervosa. In 14 patients with early onset anorexia nervosa (eight of whom had upper gastrointestinal tract symptoms), six children with other eating disorders, four children with non-ulcer dyspepsia, and 10 controls matched for age and sex, the non-invasive technique of surface electrogastrography was used to measure fasting and postprandial gastric antral electrical control activity, which underlies antral motility. The electrical signal was recorded by four bipolar silver/silver chloride electrodes attached to the upper abdomen, amplified and low pass filtered at 0.33 Hz before being displayed on a polygraph, digitised at 1 Hz, and stored on the hard disk of a personal computer for later offline analysis. Patients with non-ulcer dyspepsia had gastric antral dysrhythmias. No significant difference was found in the mean (SD) dominant frequency of the antral electrical control activity between patients with early onset anorexia nervosa (2.86 (0.35) cycles/minute (cpm)), patients with other eating disorders (3.14 (0.65) cpm), and controls (3.00 (0.46) cpm). The amplitude of electrical control activity increased postprandially in all but one subject and the fasting/postprandial amplitude ratio did not significantly differ between patients with early onset anorexia nervosa and controls, though patients with longer established disease had a smaller increase in amplitude. Gastric antral electrical dysrhythmias are not a feature of early onset anorexia nervosa and therefore do not induce or perpetuate food refusal in this disorder.

Ravelli, A M; Helps, B A; Devane, S P; Lask, B D; Milla, P J

1993-01-01

40

[Gastric motor activity in Varanus griseus lizards].  

PubMed

Motor activity of the stomach in V. griseus consists of contractions which follow the rhythm of 7-10 movements per 15 min. In contrast to tortoises, no periodic hunger activity of the stomach was observed in the lizard. Subcutaneous injection of 0.6% NaCl solution does not affect contractile activity of stomach muscles. Pilocarpine in a dose 100 microgram/kg of body weight did not change the gastrogram, doses 500 and 1,000 microgram increased the frequency and the amplitude of contractions. Atropine in a low dose (100 microgram) did not affect stomach movements. Doses 500, 1,000 and 2,000 microgram induced biphasic response. Sunflower-seed oil (10 ml) decreased twofold the frequency and the amplitude of contractions within 45-60 min. PMID:899411

Gzgzian, D M; Kuzina, M M

1977-01-01

41

Gastric myoelectrical activity as an index of emotional arousal.  

PubMed

Autonomic nervous system parameters such as electrodermal activity, heart rate, and facial EMG have been utilized extensively as measures of emotional arousal. One measure that has rarely been employed in this setting is gastric myoelectrical activity, despite the fact that "gut feelings" have an obvious and even profound role in everyday emotional life. It has been shown that the gastrointestinal system changes wall tonus and contraction rate during stressful tasks. However, the effects of emotionally salient stimuli on gastrointestinal motility have scarcely been studied. In the current study, emotional film clips designed to elicit happiness, disgust, fear, sadness, or no emotion (neutral) were presented to 16 normal participants. Electrogastrogram (EGG), skin conductance, and heart rate were measured while the participants viewed the film clips, and participants rated subjective arousal intensity and pleasantness of the film clips. We found that emotional film clips reliably induced the intended subjective feeling states. Also, EGG peak amplitudes in fear, disgust, sadness and happiness were higher than in the no emotion condition. There was a strong positive correlation (r=0.64) between EGG peak amplitude and subjective ratings of arousal. This is the first evidence that gastric myoelectrical activity is strongly correlated with arousal ratings to emotionally salient stimuli, and it suggests that EGG may add useful information about how the body contributes to the phenomenology of emotion and feeling. PMID:16403424

Vianna, E P M; Tranel, D

2006-07-01

42

Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer  

Microsoft Academic Search

Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (?-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in

M Nojima; H Suzuki; M Toyota; Y Watanabe; R Maruyama; S Sasaki; Y Sasaki; H Mita; N Nishikawa; K Yamaguchi; K Hirata; F Itoh; T Tokino; M Mori; K Imai; Y Shinomura

2007-01-01

43

Electrogastrographic study of gastric myoelectrical activity in patients with unexplained nausea and vomiting  

Microsoft Academic Search

Using cutaneous electrodes an electrogastrographic study was made of gastric myoelectrical activity in both the fasting and postprandial states in 48 patients with unexplained nausea and vomiting and in 52 control subjects. A gastric emptying study, using a radio-labelled solid phase meal, was carried out in 30 of these 48 patients. A follow up study was done after one year.

H Geldof; E J van der Schee; M van Blankenstein; J L Grashuis

1986-01-01

44

The vagal afferents discharge and myoelectrical activity in the gastric hyperalgesia model in rats.  

PubMed

A long term exposure of the gastric mucosa to inflammatory factors is suspected to alter the normal stomach motility. The consequence of it is an abnormal sensomotor response to food causing dyspeptic symptoms. Our study aimed to investigate the vagal afferents activity and the gastro-duodenal slow wave response to the mild gastric mucosa inflammation in rats. The gastric mucosal inflammation was induced by addition iodoacetamide to drinking water for 5 days. The gastro-duodenal slow wave, vagal nerve recordings and the gastric mucosa examination were performed on 6th day. The iodoacetamide irritated gastric mucosa presented the minimal inflammatory infiltration with mast cells. The vagal afferent activity was significantly increased after iodoacetamide treatment from 0.3 +/- 0.1 to 1.9 +/- 0.58 Hz, (p<0.05). The gastric slow wave accurate frequencies extracted from the fast Fourier transform spectra accelerated from 0.08 +/- 0.01 to 0.1 +/- 0.02 Hz (p<0.05). The duodenal frequencies remained unchanged (from 0.64 +/- 0.02 to 0.59 +/- 0.1 Hz). These results suggest that mild gastric mucosa irritation sensitizes vagal afferents and alters gastric but not duodenal pacemaker activity which may contribute to dyspeptic sensations. PMID:19212005

Krolczyk, G; Gil, K; Zurowski, D; Jung, A; Thor, P J

2008-12-01

45

Gastric Fullness, Physical Activity, and Proximal Extent of Gastroesophageal Reflux  

Microsoft Academic Search

OBJECTIVES:Proximal extent of gastroesophageal reflux (PER) is relevant for symptoms in GERD patients. It has been suggested that PER is determined by the volume of the refluxate that, in turn, might depend on the degree of gastric fullness. Abdominal straining, during ambulation, increases the likelihood of gastroesophageal reflux. We assessed the influence of gastric fullness and ambulation on proximal extent

Sara Emerenziani; Xin Zhang; Kathleen Blondeau; Jiri Silny; Jan Tack; Jozef Janssens; Daniel Sifrim

2005-01-01

46

Ultrasonically activated shears in extended lymphadenectomy for gastric cancer.  

PubMed

Gastrectomy, followed by extended lymphadenectomy, is the treatment of choice in some stages of advanced gastric cancer. Lymphorrhea, as a result of the many divided lymphatic vessels, increases the morbidity. Ultrasonically activated coagulated shears (UACS) may divide all small vessels followed by immediate sealing of the coapted vessel walls. We designed a prospective randomized study to determine the effectiveness of the UACS versus monopolar electrosurgery in D2 dissection. Forty patients with gastric cancer stage II or stage IIIA were enrolled and randomized into 2 groups of 20 patients each. Group A underwent lymphatic dissection with monopolar cautery. Group B underwent lymphatic dissection with UACS. Subhepatic and left sudiaphragmatic closed drains were left until lymphorrhea and/or oozing stopped. Total gastrectomy was performed in 16 patients of group A and 14 of group B; subtotal gastrectomy was performed in 4 patients in group A and 6 patients in group B. The drains were removed after 6-17 days (mean 9.7 +/- 2.9) in group Aand after 4-8 days (mean 5.6 +/- 1.2) in group B(p < 0.001). The total amount of drained fluid was 300-2050 ml (mean 985 +/- 602) in group A and 230-1080 ml (mean 480 +/- 242) in group B (p < 0.002). Eight patients in group A and 5 in group B had postoperative fever, while 3 and 1 patients, respectively, had wound infections. In conclusion the use of UACS is a safe method of lymphatic dissection which reduces operative blood loss, postoperative lymphorrhea, blood transfusions,and hospital stay. PMID:11865342

Tsimoyiannis, Evangelos C; Jabarin, Mochammed; Tsimoyiannis, John C; Betzios, John P; Tsilikatis, Christos; Glantzounis, George

2002-02-01

47

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb.  

PubMed

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30-1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H+, K+-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H+, K+, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity. PMID:18579323

Twardowschy, André; Freitas, Cristina Setim; Baggio, Cristiane Hatsuko; Mayer, Bárbara; dos Santos, Ana Cristina; Pizzolatti, Moacir Geraldo; Zacarias, Aline Alvarez; dos Santos, Elide Pereira; Otuki, Michel Fleith; Marques, Maria Consuelo Andrade

2008-08-13

48

Static magnetic field inhibits adenosine deaminase activity in cancerous and noncancerous human gastric tissues.  

PubMed

Abstract Aim: Investigation of possible effects of static magnetic field (SMF) on adenosine deaminase (ADA) activity in cancerous and noncancerous human gastric and colon tissues to obtain information about possible action mechanism of SMF. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues removed from patients by surgical operations were used in the studies. SMF was created by using two static magnets. Before and after treatment with SMF, ADA activities in the tissue samples were measured. Results: The ADA activity was found to be lowered in gastric tissues treated with the SMF. However, no change was observed in the ADA activity of colon tissues. Conclusions: Our results suggest that SMF inhibits the ADA enzyme in gastric tissues significantly. It is supposed that, in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of the ADA enzyme might also play a part in the anticancer activity of SMF. PMID:24784458

Durak, Zahide Esra; Kocao?lu, Ender Hilmi; Oztürk, Bahad?r

2014-05-01

49

Activation of Mesenchymal Stem Cells by Macrophages Prompts Human Gastric Cancer Growth through NF-?B Pathway  

PubMed Central

Accumulating evidence indicate that macrophages activate mesenchymal stem cells (MSCs) to acquire pro-inflammatory phenotype. However, the role of MSCs activated by macrophages in gastric cancer remains largely unknown. In this study, we found that MSCs were activated by macrophages to produce increased levels of inflammatory cytokines. Cell colony formation and transwell migration assays revealed that supernatants from the activated MSCs could promote both gastric epithelial cell and gastric cancer cell proliferation and migration. In addition, the expression of epithelial-mesenchymal transition (EMT), angiogenesis, and stemness-related genes was increased in activated MSCs. The phosphorylated forms of NF-?B, ERK and STAT3 in gastric cells were increased by active MSCs. Inhibition of NF-?B activation by PDTC blocked the effect of activated MSCs on gastric cancer cells. Co-injection of activated MSCs with gastric cancer cells could accelerate gastric cancer growth. Moreover, human peripheral blood monocytes derived macrophages also activated MSCs to prompt gastric cancer cell proliferation and migration. Taken together, our findings suggest that MSCs activated by macrophage acquire pro-inflammatory phenotype and prompt gastric cancer growth in an NF-?B-dependent manner, which provides new evidence for the modulation of MSCs by tumor microenvironment and further insight to the role of stromal cells in gastric carcinogenesis and cancer progression.

Wang, Mei; Zhang, Jie; Huang, Feng; Cai, Jie; Zhang, Qiang; Mao, Fei; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-01-01

50

Histamine, cAMP, and activation of piglet gastric mucosa.  

PubMed

The involvement of cAMP as a second messenger for histamine-induced H+ secretion was studied in a physiologically active, in vitro preparation of piglet gastric mucosa. During the first 5--10 min of stimulation with either histamine or the cAMP phosphodiesterase inhibitor 3-isobutyl-1,4-methylxanthine (IBMX), increases (greater than or equal to 5-fold) in tissue cAMP content [(c-AMP]) were well correlated with the characteristic decrease in transepithelial resistance (R); these changes precede H+ secretion by several minutes. Control experiments indicate that, during these treatments, tissue [cAMP] is dominated by the [cAMP] of oxyntic cells alone; change in R and H+ are also related to activity of these cells alone. At the steady state (45 min), histamine and IBMX caused equivalent increases in H+ and decreases in R, but [cAMP] was markedly different in the two cases. With IBMX [cAMP] was elevated at least fivefold, whereas with histamine [cAMP] was less than or equal to 50% above resting levels. The tissue is also stimulated by exogenous additions of dibutyryl cAMP. A histamine-sensitive adenylate cyclase was present in isolated, purified oxyntic cells. The histamine sensitivity of the cyclase was very similar to that which the intact tissue exhibits for histamine-induced changes in H+ and R. The cyclase activity was blocked by cimetidine but not by promethazine. We conclude that during stimulation histamine activates a histamine (H2)-sensitive adenylate cyclase of oxyntic cells, and there is a rapid increase in cellular [cAMP] that is involved in activation of H+ transport and other associated changes of oxyntic cells. An active phosphodiesterase is responsible for reducing [cAMP] to a level much below the "peak" value. Other cellular factors (e.g. protein kinases and Ca2+-calmodulin) must also be involved in the maintenance of the stimulated state of oxyntic cells. PMID:6175225

Machen, T E; Rutten, M J; Ekblad, E B

1982-02-01

51

Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats  

PubMed Central

The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers.

Sakat, S. S.; Tupe, Preeti; Juvekar, Archana

2012-01-01

52

Detection of gelatinase B activity in serum of gastric cancer patients  

PubMed Central

AIM: To determine the proteolytic activity and expression of gelatinase B in serum of gastric cancer patients and their correlation with the stage of the tumor. METHODS: Sera from 23 patients who underwent surgery for primary gastric cancer as the experimental group and from 11 as the control group were used to determine the proteolytic activity and its inhibition by EDTA and 1,10-phenanthroline. Gelatinase B activity was detected by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-PAGE zymography. RESULTS: Proteolytic enzyme activity was increased in gastric cancer patients when compared to the control group (P<0.05). The proteinases were determined to be metalloproteinases upon inhibition test with specific metalloproteinase inhibitors 1,10-phenanthroline (P<0.05) and EDTA (P <0.01). SDS-PAGE and SDS-PAGE zymography revealed gelatinase B (proMMP-9) activity and its molecular mass of 92 ku. CONCLUSION: Proteinase activity is overexpressed in serum of gastric cancer patients. Gelatinase B in serum plays an important role in the progression of gastric cancer. ProMMP-9 can be used as a marker for invasiveness of gastric cancer.

Dragutinovic, Vesna V; Radovanovic, Nebojsa S; Izrael-Zivkovic, Lidija T; Vrvic, Miroslav M

2006-01-01

53

Activation of HER family members in gastric carcinoma cells mediates resistance to MET inhibition  

PubMed Central

Background Gastric cancer is the second leading cause of cancer mortality in the world. The receptor tyrosine kinase MET is constitutively activated in many gastric cancers and its expression is strictly required for survival of some gastric cancer cells. Thus, MET is considered a good candidate for targeted therapeutic intervention in this type of tumor, and MET inhibitors recently entered clinical trials. One of the major problems of therapies targeting tyrosine kinases is that many tumors are not responsive to treatment or eventually develop resistance to the drugs. Perspective studies are thus mandatory to identify the molecular mechanisms that could cause resistance to these therapies. Results Our in vitro and in vivo results demonstrate that, in MET-addicted gastric cancer cells, the activation of HER (Human Epidermal Receptor) family members induces resistance to MET silencing or inhibition by PHA-665752 (a selective kinase inhibitor). We provide molecular evidences highlighting the role of EGFR, HER3, and downstream signaling pathways common to MET and HER family in resistance to MET inhibitors. Moreover, we show that an in vitro generated gastric cancer cell line resistant to MET-inhibition displays overexpression of HER family members, whose activation contributes to maintenance of resistance. Conclusions Our findings predict that gastric cancer tumors bearing constitutive activation of HER family members are poorly responsive to MET inhibition, even if this receptor is constitutively active. Moreover, the appearance of these alterations might also be responsible for the onset of resistance in initially responsive tumors.

2010-01-01

54

Environmental noise alters gastric myoelectrical activity: Effect of age  

PubMed Central

AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in random order, to three auditory stimuli (Hospital noise, conversation babble and traffic noise) after a 20-min baseline. All periods lasted 20 min and were interspersed with a 10 min of recovery. GMA was obtained using a Synectics Microdigitrapper. Autonomic nerve function was assessed by monitoring blood pressure and heart rate using an automatic recording device. RESULTS: Dominant power tended to decrease with increase of age (P < 0.05). The overall percentage of three cycle per minute (CPM) activity decreased during exposure to hospital noise (12.0%, P < 0.05), traffic noise (13.9%, P < 0.05), and conversation babble (7.1%). The subjects in the younger group (< 50 years) showed a consistent reduction in the percentage of 3 CPM activity during hospital noise (22.9%, P < 0.05), traffic noise (19.0%, P < 0.05), and conversation babble (15.5%). These observations were accompanied by a significant increase in bradygastria: hospital noise (P < 0.05) and traffic noise (P < 0.05). In contrast, the subjects over 50 years of age did not exhibit a significant decrease in 3 CPM activity. Regardless of age, noise did not alter blood pressure or heart rate. CONCLUSION: GMA changes with age. Loud noise can alter GMA, especially in younger individuals. Our data indicate that even short-term exposure to noise may alter the contractility of the stomach.

Castle, James S; Xing, Jin-Hong; Warner, Mark R; Korsten, Mark A

2007-01-01

55

High antitumor activity of pladienolide B and its derivative in gastric cancer.  

PubMed

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction. PMID:24635824

Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji

2014-01-01

56

ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats  

PubMed Central

AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis. METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry. RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins. CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis.

Chen, Xia; Fu, Xiang-Sheng; Li, Chang-Ping; Zhao, Hong-Xian

2014-01-01

57

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants  

PubMed Central

Summary In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. Introduction Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. Methods Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. Results Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P=0.004 and P=0.039 respectively). Change in maximal acid output was similar in the two groups (P=0.995). As expected, cinacalcet produced significant decreases in serum PTH (P<0.001) and ionized calcium levels (P=0.032), and increases in serum phosphorus levels (P=0.001) and urinary calcium (P=0.023). Conclusions This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Ceglia, L.; Harris, S. S.; Rasmussen, H. M.; Dawson-Hughes, B.

2009-01-01

58

The role of plasminogen activator inhibitor-1 in gastric mucosal protection  

PubMed Central

Gastric mucosal health is maintained in response to potentially damaging luminal factors. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt protective mechanisms leading to bleeding and ulceration. The plasminogen activator system has been implicated in fibrinolysis following gastric ulceration, and an inhibitor of this system, plasminogen activator inhibitor (PAI)-1, is expressed in gastric epithelial cells. In Helicobacter pylori-negative patients with normal gastric histology taking aspirin or NSAIDs, we found elevated gastric PAI-1 mRNA abundance compared with controls; the increase in patients on aspirin was independent of whether they were also taking proton pump inhibitors. In the same patients, aspirin tended to lower urokinase plasminogen activator mRNA. Immunohistochemistry indicated PAI-1 localization to epithelial cells. In a model system using MKN45 or AGS-GR cells transfected with a PAI-1 promoter-luciferase reporter construct, we found no evidence for upregulation of PAI-1 expression by indomethacin, and, in fact, cyclooxygenase products such as PGE2 and PGI2 weakly stimulated expression. Increased gastric PAI-1 mRNA was also found in mice following gavage with ethanol or indomethacin, but plasma PAI-1 was unaffected. In PAI-1?/? mice, gastric hemorrhagic lesions in response to ethanol or indomethacin were increased compared with C57BL/6 mice. In contrast, in PAI-1-H/K? mice in which PAI-1 is overexpressed in parietal cells, there were decreased lesions in response to ethanol and indomethacin. Thus, PAI-1 expression is increased in gastric epithelial cells in response to mucosal irritants such as aspirin and NSAIDs probably via an indirect mechanism, and PAI-1 acts as a local autoregulator to minimize mucosal damage.

Kenny, Susan; Steele, Islay; Lyons, Suzanne; Moore, Andrew R.; Murugesan, Senthil V.; Tiszlavicz, Laszlo; Dimaline, Rod; Pritchard, D. Mark; Varro, Andrea

2013-01-01

59

Refractory death rattle: deep aspiration facilitates the effects of antisecretory agents.  

PubMed

Anticholinergic drugs, including atropine, hyoscine butylbromide, and scopolamine, have been shown to be equally effective in the treatment of death rattle. However, anticholinergic drugs may only be effective in reducing the production of further secretions, rather than eliminating the existing ones. A case is described in which a preventive procedure was undertaken to carefully eliminate secretions before starting anticholinergic drugs. Airway aspiration under light anesthesia removed secretions before starting anticholinergic drugs. Low doses of propofol were given intravenously to make a laryngoscopy feasible, allowing the complete aspiration of large amounts of tracheal secretions. No death rattle was perceived until death. Relatives were satisfied with the treatment and the peaceful death. Antisecretory agents may only prevent further accumulation of fluids along the airways and in the pharynx. The use of these drugs, supplemented by this aspiration procedure in carefully selected patients, may help eliminate death rattle in patients with advanced illness who are unable to cough or swallow. Explanation and reassurance to relieve fears and concerns regarding a procedure aimed to improve the quality of end-of-life care are of paramount importance, and active collaboration in decision making facilitates a timely intervention. This preliminary experience may help further research on the best treatment at the end of life. PMID:21131169

Mercadante, Sebastiano; Villari, Patrizia; Ferrera, Patrizia

2011-03-01

60

Inhibitory Activities of Palmatine from Coptis chinensis Against Helicobactor pylori and Gastric Damage  

PubMed Central

Helicobacter pylori (H. pylori) is the most important factor of gastric disease in clinical practice. Moreover, smoking, stress and a poor diet may be additive factors for gastric damage. With these factors, increasing infection of H. pylori triggers gastritis, gastric ulcers and gastric cancer. To develop a new protective agent, we are concerned with plant-derived extract. The extract of Coptis chinensis (C. chinensis) and its constituents were investigated to assess their protective activities against gastric damage. The C. chinensis extract showed a scavenging effect against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, inhibition of H. pylori colonization and antiulcerogenic activities in rat. In particular, palmatine derived from C. chinensis was found to be the novel protective agent. It is better than the C. chinensis extract, berberine, a well-known constituent of C. chinensis. We suggest that palmatine from the root cortex of C. chinensis may be a good candidate for the development of new pharmaceuticals to prevent gastric disease.

Jung, Joohee; Choi, Jae Sue

2014-01-01

61

Inhibitory Activities of Palmatine from Coptis chinensis Against Helicobactor pylori and Gastric Damage.  

PubMed

Helicobacter pylori (H. pylori) is the most important factor of gastric disease in clinical practice. Moreover, smoking, stress and a poor diet may be additive factors for gastric damage. With these factors, increasing infection of H. pylori triggers gastritis, gastric ulcers and gastric cancer. To develop a new protective agent, we are concerned with plant-derived extract. The extract of Coptis chinensis (C. chinensis) and its constituents were investigated to assess their protective activities against gastric damage. The C. chinensis extract showed a scavenging effect against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, inhibition of H. pylori colonization and antiulcerogenic activities in rat. In particular, palmatine derived from C. chinensis was found to be the novel protective agent. It is better than the C. chinensis extract, berberine, a well-known constituent of C. chinensis. We suggest that palmatine from the root cortex of C. chinensis may be a good candidate for the development of new pharmaceuticals to prevent gastric disease. PMID:24795799

Jung, Joohee; Choi, Jae Sue; Jeong, Choon-Sik

2014-03-01

62

Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor activity and emptying.  

PubMed

It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not endogenous PGs, which can protect the stomach from noxious stimuli, affect gastric motor activity and emptying. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of over 2 cmH(2)O. Replacement of intragastric physiological saline with 1 M NaCl solution significantly increased PGI(2) and PGE(2) in stomach and suppressed the myoelectrical activity under a pressure of 2 cmH(2)O by 70%. Indomethacin inhibited the suppression of myoelectrical activity by 1 M NaCl. The myoelectrical activity under a pressure of 2 cmH(2)O was suppressed by continuous infusion of a selective EP1 agonist (ONO-DI-004, 3-100 nmol·kg(-1)·min(-1)) into the gastric artery in a dose-dependent manner, but not by that of the PGI receptor agonist beraprost sodium (100 nmol·kg(-1)·min(-1)). Suppression of myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a selective EP1 antagonist (ONO-8711, 100 nmol·kg(-1)·min(-1)) into the gastric artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their wild-type counterparts. Gastric emptying was strongly suppressed with intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression was not seen in EP1 knockout mice. These results suggest that PGE(2)-EP1 signaling has crucial roles in suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying and that EP1 is an obvious target for drugs that control gastric emptying. PMID:20798358

Mizuguchi, Sumito; Ohno, Takashi; Hattori, Youichiro; Ae, Takako; Minamino, Tsutomu; Satoh, Takehito; Arai, Katsuharu; Saeki, Takeo; Hayashi, Izumi; Sugimoto, Yukihiko; Narumiya, Shuh; Saigenji, Katsunori; Majima, Masataka

2010-11-01

63

[Cerebral hemorrhagic stroke and gastric myoelectric activity. Case report].  

PubMed

We showed case of subarachnoid hemorrhage with massive intracerebral hematoma of the left hemisphere and associating gastric myoelectrical disturbances. The cerebral angiography did not show vascular malformation. The electrogastrogram (EGG) at 2 days after the onset of neurological symptoms revealed tachygastria up to 66.7% of the recording time. PMID:16261874

Madroszkiewicz, Dorota; Czepko, Ryszard; Thor, Piotr J; Furga?a, Agata

2004-01-01

64

Normal gastric antral myoelectrical activity in early onset anorexia nervosa  

Microsoft Academic Search

Anorexia, epigastric discomfort, nausea, and vomiting may result from disordered gastric motility and emptying. These features have been found in many adults with anorexia nervosa, but have never been investigated in early onset anorexia nervosa. In 14 patients with early onset anorexia nervosa (eight of whom had upper gastrointestinal tract symptoms), six children with other eating disorders, four children with

A M Ravelli; B A Helps; S P Devane; B D Lask; P J Milla

1993-01-01

65

Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.  

PubMed

Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. PMID:21925651

Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

2011-10-24

66

In vitro antioxidative activity of yellow tea and its in vivo preventive effect on gastric injury  

PubMed Central

Yellow tea is a traditional Chinese drink widely used in Asia. The aim of this study was to determine the antioxidant activity of yellow tea and its preventive effect on gastric injury. The antioxidant effects were determined by measuring the 1,1-diphenyl-2-picryhydrazyl (DPPH) free radical- and hydroxyl radical-scavenging activity. The yellow tea extract demonstrated high antioxidant activity in the assays of DPPH and hydroxyl radical-scavenging activity. Additionally, an animal model was used to investigate the preventive effect of yellow tea on gastric injury. High concentrations of yellow tea reduced the levels of the serum pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-? to a greater extent than low concentrations. The extent of the gastric injury was significantly reduced by yellow tea, which demonstrated its anti-inflammatory properties. Yellow tea demonstrated the strongest inhibitory effect (74.6%) against gastric injury when administered at a dose of 1,000 mg/kg by gavage. These results suggest that yellow tea possesses good antioxidant activity and a preventive effect on gastric injury in vivo.

WANG, QIANG; ZHAO, XIN; QIAN, YU; WANG, RUI

2013-01-01

67

Physical Activity and Esophageal and Gastric Carcinoma in a Large Prospective Study  

PubMed Central

Background Few studies have investigated the relationship of physical activity to esophageal and gastric carcinoma according to histology and anatomic site. Methods This study prospectively investigated the association between physical activity and esophageal and gastric carcinoma in a cohort of 487,732 U.S. men and women, followed from 1995–1996 to December 31, 2003. All analyses were performed in 2007– 2008. Results During 8 years of follow-up study, 523 cases of esophageal carcinoma (149 squamous cell and 374 adenocarcinoma) and 642 cases of gastric carcinoma (313 cardia and 329 noncardia) were documented. Physical activity was associated with reduced risk of esophageal and gastric adenocarcinomas but was unrelated to esophageal squamous cell carcinoma. The inverse association with physical activity was strongest for gastric noncardia adenocarcinoma (multivariate relative risk [RR] for highest versus lowest physical activity level=0.62, 95% CI=0.44, 0.87). Relationships were weaker but evident for gastric cardia adenocarcinoma (RR=0.83; 95% CI=0.58, 1.19) and esophageal adenocarcinoma (RR=0.75; 95% CI=0.53, 1.06). No significant relationship with physical activity was observed for esophageal squamous cell carcinoma (RR=1.05; 95% CI=0.64, 1.74). Exclusion of cases diagnosed during the first 2 follow-up years did not change those estimates, indicating that the findings are not due to decreased activity levels among participants with undiagnosed cancer at entry. Conclusions Physical activity may play a role in the prevention of upper gastrointestinal tract adenocarcinomas. No association was seen between physical activity and esophageal squamous cell carcinoma.

Leitzmann, Michael F.; Koebnick, Corinna; Freedman, Neal D.; Park, Yikyung; Ballard-Barbash, Rachel; Hollenbeck, Albert; Schatzkin, Arthur; Abnet, Christian C.

2009-01-01

68

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway  

PubMed Central

Increasing evidence suggests that cytosolic non-specific dipeptidase 2 (CNDP2) appears to do more than just perform an enzymatic activity; it is functionally important in cancers as well. Here, we show that the expression of CNDP2 is commonly down-regulated in gastric cancer tissues. The ectopic expression of CNDP2 resulted in significant inhibition of cell proliferation, induction of cell apoptosis and cell cycle arrest, and suppressed gastric tumor growth in nude mice. We further revealed that the reintroduction of CNDP2 transcriptionally upregulated p38 and activated c-Jun NH2-terminal kinase (JNK), whereas the loss of CNDP2 increased the phosphorylation of extracellular signal–related kinase (ERK). These results suggest that CNDP2 acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway.

Zhang, Zhenwei; Miao, Lei; Xin, Xiaoming; Zhang, Jianpeng; Yang, Shengsheng; Miao, Mingyong; Kong, Xiangping; Jiao, Binghua

2014-01-01

69

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.  

PubMed

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine. PMID:18434110

Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

2008-09-01

70

Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice  

PubMed Central

Studies in rats suggest that PACAP modulates gastric acid secretion through the release of both histamine and somatostatin. We characterized the effects of exogenous PACAP on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula and in conscious 2-h pylorus ligated mice, and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. Urethane-anesthetized wild-type mice had low basal acid secretion (0.10±0.01 ?mol (10 min)?1) compared with SSTR2 knockout mice (0.93±0.07 ?mol (10 min)?1). Somatostatin antibody and PRL-2903 increased basal secretion in wild-type mice but not in SSTR2 knockout animals. In wild-type urethane-anesthetized mice, PACAP-38 (3–270 ?g kg?1 h?1) did not affect the low basal acid secretion, but inhibited the acid response to pentagastrin, histamine, and bethanechol. In wild-type urethane-anesthetized mice pretreated with somatostatin antibody or PRL-2903 and in SSTR2 knockout mice, peripheral infusion of PACAP-38 or somatostatin-14 did not inhibit the increased basal gastric acid secretion. In conscious wild-type mice, but not in SSTR2 knockout mice, PACAP-38 inhibited gastric acid secretion induced by 2-h pylorus ligation. The antisecretory effect of PACAP-38 was prevented by immunoneutralization of somatostatin. These results indicate that, in mice, peripheral PACAP inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2 receptors. There is no evidence for stimulatory effects of PACAP on acid secretion in mice.

Piqueras, Laura; Tache, Yvette; Martinez, Vicente

2004-01-01

71

Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility  

PubMed Central

This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase in mucosal permeability, neutrophil infiltration and oxyradical production, and eventually producing gastric lesions. These lesions are prevented by pretreatment with PGE2 and antisecretory drugs, and also via an atropine-sensitive mechanism, not related to antisecretory action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach, the combined administration of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases prostaglandin E2 (PGE2) production and causes gastric hypermotility and an increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions, including adrenalectomy, arthritis, and Helicobacter pylori-infection. In summary, gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility, and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.

Takeuchi, Koji

2012-01-01

72

Changes in gastric myoelectrical activity in hypertrophic pyloric stenosis and after surgical correction.  

PubMed

The changes of gastric myoelectrical activity were investigated in 20 infants by cutaneous electrogastrography (EGG) before and after the surgical correction of infantile hypertrophic pyloric stenosis (IHPS). The dominance of 2-4 cycles per minute (CPM) "slow waves" is typical of the healthy gastric function. The shift of the dominant frequencies towards the slower frequency (0-2 CPM) is defined as bradygastria, whereas a shift towards the more frequent waves (4-10 CPM) is called tachygastria. Unlike with healthy infants, the electrogastrogram showed pathologic patterns in 85% (18 out of 20) of IHPS patients. In all except two of these infants with pathologic electrical patterns, the frequency of the waves significantly shifted towards tachygastria. The effect of feeding on the gastric myoelectrical activity could only be studied in limited (9/20) cases because of recurring vomiting during the preoperative period. In IHPS infants, a significant increase in the bradygastria group was observed in the postprandial period compared with healthy infants. Three to 5 days after surgical repair (pyloromyotomy) and the reintroduction of feeding in gradually increasing amounts, the gastric myoelectrical activity showed physiologic patterns again, showing that the pyloric function was back to normal. Cutaneous EGG is a useful, noninvasive method to obtain indirect information about the motor function of the stomach and might be further applicable to pediatric gastric motility disorders. PMID:15179517

Bókay, J; Kis, E; Verebély, T

2004-05-01

73

Antisecretory Agents for Prevention of Post-ERCP Pancreatitis: Rationale for Use and Clinical Results  

Microsoft Academic Search

Summary Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Over the past decade, there has been notable research on the use of various prophylactic agents in preventing post-ERCP pancreatitis. The most widely investigated drug is the antisecretory agent somatostatin and its analogue octreotide. Both agents are potent inhibitors of exocrine secretion of the pancreas, which plays

Ronnie Tung-Ping Poon; Sheung Tat Fan

74

STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells  

Microsoft Academic Search

Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the role of STAT3 signaling in apoptosis and cellular proliferation in gastric cancer.

Naoki Kanda; Hiroshi Seno; Yoshitaka Konda; Hiroyuki Marusawa; Masashi Kanai; Toshio Nakajima; Tomoko Kawashima; Apichart Nanakin; Tateo Sawabu; Yoshito Uenoyama; Akira Sekikawa; Mayumi Kawada; Katsumasa Suzuki; Takahisa Kayahara; Hirokazu Fukui; Mitsutaka Sawada; Tsutomu Chiba; H Seno

2004-01-01

75

Gastroprotective activity of ?-terpineol in two experimental models of gastric ulcer in rats  

PubMed Central

Background and the purpose of the study Several plant essential oils, as well as terpenes present in essential oils, have shown gastroprotective activity. The aim of the present work was to evaluate the gastroprotective activity of ?-terpineol, a monoterpene alcohol which is present in essential oils of various plants. Methods The gastroprotective activity of ?-terpineol was evaluated in rats by assessing the changes in ethanol and indomethacin-induced gastric ulcer scores and on gastric secretory volume and total acidity in pylorus-ligated rats. Alpha-terpineol was administrated orally at the doses of 10, 30, and 50 mg/kg one hour before administration of the ulcer inducing agents by the pylorus ligation procedure. The involvement of endogenous prostaglandins in the protective effect of ?-terpineol in ethanol-induced gastric lesions test was assessed by administration of indomethacin (10 mg/kg, s.c.) 30 min before oral administration of ?-terpineol at the dose of 50 mg/kg. Results ?-terpineol presented gastroprotective activity against ethanol-induced ulcers at the doses of 10, 30, and 50 mg/kg. Epoxy-carvone at the dose of 10 mg/kg did not present gastroprotective activity against ulcer induced by indomethacin, but at the doses of 30 and 50 mg/kg it attenuated the gastric damages induced by this agent significantly. Pretreatment with indomethacin did not prevent the gastroprotective effect of ?-terpineol on ethanol-induced ulcers. Alpha-terpineol also did not affect the gastric secretion in pylorus-ligated rats. Major conclusion The results suggest that ?-terpineol presents gastroprotective action which does not involve either an increase in the synthesis of endogenous prostaglandin or a decrease in the gastric acid secretion.

Souza, RHL.; Cardoso, MSP.; Menezes, CT.; Silva, JP.; De Sousa, DP.; Batista, JS.

2011-01-01

76

Evaluation of antioxidant and immuno-enhancing activities of Purslane polysaccharides in gastric cancer rats.  

PubMed

In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from plant or animal and used as a promising source of therapeutic agents for cancer. In this study, we examined the effects of Purslane polysaccharides (PPs) on the oxidative injury and immune status in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. PPs administration (200, 400 or 800mg/kg body weight) could not only increase the body weight, peripheral white blood cells (WBC) count, thymus and spleen indexes, but also remarkably promote splenocytes proliferation of gastric cancer rats. Furthermore, the production of serum cytokines in gastric cancer rats, such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-?) was enhanced by PPs treatment. Besides, treatment with PPs was found to provide a dose-dependent protection against MNNG-induced oxidative injury by enhancing SOD, CAT, GSH-Px activities of gastric cancer rats. Taken together, we concluded that enhancement of antioxidants and immune response might be responsible for the anticancer effect of PPs in gastric cancer. PMID:24768972

Li, Yunqiao; Hu, Yanke; Shi, Shaojun; Jiang, Lei

2014-07-01

77

Diverse mechanisms of Wnt activation and effects of pathway inhibition on proliferation of human gastric carcinoma cells  

Microsoft Academic Search

Human gastric carcinomas are among the most treatment-refractory epithelial malignancies. Increased understanding of the underlying molecular aberrations in such tumors could provide insights leading to improved therapeutic approaches. In this study, we characterized diverse genetic aberrations leading to constitutive Wnt signaling activation in a series of human gastric carcinoma cell lines. Downregulation of TCF signaling by stable transduction of dominant

S Asciutti; G Akiri; L Grumolato; S Vijayakumar; S A Aaronson

2011-01-01

78

Synchronized dual pulse gastric electrical stimulation induces activation of enteric glial cells in rats with diabetic gastroparesis.  

PubMed

Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES) on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7-14-day diabetes and 56-63-day diabetes before and after stimulation and the age-matched control groups. SGES-60?mins and SGES-7 days (60?mins/day) were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1) Gastric emptying was accelerated in 7-14-day diabetes and delayed in 56-63-day diabetes. (2) The S100B expression in 56-63-day diabetes decreased and the ultrastructure changed. (3) The age-associated loss of EGC was observed in 56-63-day control group. (4) SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5) The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60?mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation. PMID:24860604

Yang, Wei; Wang, Nian; Shi, Xue; Chen, Jie

2014-01-01

79

Synchronized Dual Pulse Gastric Electrical Stimulation Induces Activation of Enteric Glial Cells in Rats with Diabetic Gastroparesis  

PubMed Central

Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES) on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7–14-day diabetes and 56–63-day diabetes before and after stimulation and the age-matched control groups. SGES-60?mins and SGES-7 days (60?mins/day) were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1) Gastric emptying was accelerated in 7–14-day diabetes and delayed in 56–63-day diabetes. (2) The S100B expression in 56–63-day diabetes decreased and the ultrastructure changed. (3) The age-associated loss of EGC was observed in 56–63-day control group. (4) SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5) The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60?mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation.

Yang, Wei; Wang, Nian; Shi, Xue; Chen, Jie

2014-01-01

80

Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells.  

PubMed

Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and we recently showed that lipid raft-regulated epidermal growth factor receptor (EGFR) activation antagonized TRAIL-induced apoptosis. However, it is not clear whether caveolin-1, an essential structural constituent of lipid rafts, regulates lipid raft-mediated EGFR activation. We report here that TRAIL induced the translocation of EGFR into lipid rafts and its activation in gastric cancer SGC-7901 and MGC-803 cells. Simultaneously, caveolin-1 was also activated. Knockdown of caveolin-1 partially prevented EGFR activation and increased TRAIL sensitivity. Moreover, TRAIL promoted the translocation of Src into lipid rafts and its activation, as well as the interaction of Src with both EGFR and caveolin-1. A Src inhibitor prevented these interactions and the activation of caveolin-1 and EGFR, and thus enhanced TRAIL-induced apoptosis. These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells. PMID:24840271

Xu, Ling; Qu, Xiujuan; Li, Heming; Li, Ce; Liu, Jing; Zheng, Huachuan; Liu, Yunpeng

2014-07-01

81

Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects - a correlation study  

PubMed Central

We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes, and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in MGG and in mucosal electrodes (r =0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes.

Somarajan, S; Muszynski, ND; Obioha, C; Richards, WO; Bradshaw, LA

2012-01-01

82

Ca2+ and Ca2+Activated K+ Currents in Mammalian Gastric Smooth Muscle Cells  

Microsoft Academic Search

Inward movement of calcium through voltage-dependent channels in muscle is thought to initiate the action potential and trigger contraction. Calcium-activated potassium channels carry large outward potassium currents that may be responsible for membrane repolarization. Calcium and calcium-activated potassium currents were identified in enzymatically isolated mammalian gastric myocytes. These currents were blocked by cadmium and nifedipine but were not substantially affected

Raman Mitra; Martin Morad

1985-01-01

83

Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping  

PubMed Central

Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm2) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3–4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 ± 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies.

Du, Peng; Cheng, Leo K.; Egbuji, John U.; Lammers, Wim J. E. P.; Windsor, John A.; Pullan, Andrew J.

2010-01-01

84

Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity  

NASA Technical Reports Server (NTRS)

This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.

Uijtdehaage, S. H.; Stern, R. M.; Koch, K. L.

1992-01-01

85

Leptin activates STAT and ERK2 pathways and induces gastric cancer cell proliferation  

SciTech Connect

Although leptin is known to induce proliferative response in gastric cancer cells, the mechanism(s) underlying this action remains poorly understood. Here, we provide evidence that leptin-induced gastric cancer cell proliferation involves activation of STAT and ERK2 signaling pathways. Leptin-induced STAT3 phosphorylation is independent of ERK2 activation. Leptin increases SHP2 phosphorylation and enhances binding of Grb2 to SHP2. Inhibition of SHP2 expression with siRNA but not SHP2 phosphatase activity abolished leptin-induced ERK2 activation. While JAK inhibition with AG490 significantly reduced leptin-induced ERK2, STAT3 phosphorylation, and cell proliferation, SHP2 inhibition only partially reduced cancer cell proliferation. Immunostaining of gastric cancer tissues displayed local overexpression of leptin and its receptor indicating that leptin might be produced and act locally in a paracrine or autocrine manner. These findings indicate that leptin promotes cancer growth by activating multiple signaling pathways and therefore blocking its action at the receptor level could be a rational therapeutic strategy.

Pai, Rama [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States)]. E-mail: rpai@uci.edu; Lin Cal [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States); Tran, Teresa [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States); Tarnawski, Andrzej [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States)]. E-mail: atarnawski@yahoo.com

2005-06-17

86

Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles.  

PubMed

The effects of red sap from Croton lechleri (SdD), Euphorbiaceae, on vascular and gastric smooth muscles were investigated. SdD, from 10 to 1000 microg/ml, induced concentration-dependent vasoconstriction in rat caudal arteries, which was endothelium-independent. In arterial preparations pre-constricted by phenylephrine (0.1 microM) or KCl (30 mM), SdD also produced concentration-dependent vasoconstriction. To study the mechanisms implicated in this effect we used selective inhibitors such as prazosin (0.1 microM), an antagonist of alpha(1)-adrenoceptors, atropine (0.1 microM), an antagonist of muscarinic receptors, and ritanserin (50 nM), a 5-HT(2A) antagonist; none of these influenced vasoconstriction caused by SdD. Likewise, nifedipine (50 nM), an inhibitor of L-type calcium channels, did not modify the action of SdD. Capsaicin (100 nM), an agonist of vanilloid receptors, also did not affect vasoconstriction by SdD. We also investigated the action of SdD (10-1000 microg/ml) on rat gastric fundus; per se the sap slightly increased contractile tension. When the gastric fundus was pre-treated with SdD (100 microg/ml) the contraction induced by carbachol (1 microM) was increased, whereas that by KCl (60mM) or capsaicin (100 nM) were unchanged. The data shows that SdD increased contractile tension in a concentration-dependent way, both on vascular and gastric smooth muscles. The vasoconstriction is unrelated to alpha(1), M, 5-HT(2A) and vanilloid receptors as well as L-type calcium channels. SdD increased also contraction by carbachol on rat gastric fundus. Thus for the first time, experimental data provides evidence that sap from C. lechleri owns constricting activity on smooth muscles. PMID:19406630

Froldi, G; Zagotto, G; Filippini, R; Montopoli, M; Dorigo, P; Caparrotta, L

2009-08-01

87

Role of c-Src activity in the regulation of gastric cancer cell migration.  

PubMed

Gastric cancer is associated with increased migration and invasion. In the present study, we explored the role of c-Src in gastric cancer cell migration and invasion. BGC-823 gastric cancer cells were used to investigate migration following treatment of these cells with the c-Src inhibitors, PP2 and SU6656. Migration and invasion were analyzed by wound healing and Transwell assays. Western blot analysis was used to detect the expression of MT1-MMP and VEGF-C, while the activity of MMP2 and MMP9 was monitored with gelatin zymography assay. Immunoprecipitation was used to detect interactions among furin, pro-MT1-MMP and pro-VEGF-C. MT1-MMP and VEGF-C expression levels were inhibited by PP2 and SU6656 treatment, in accordance with decreased c-Src activity. Similarly, the zymography assay demonstrated that the activity of MMP2 and MMP9 was decreased following PP2 or SU6656 treatment. Blockade of c-Src also inhibited the invasive and migratory capacity of BGC-823 cells. Notably, c-Src interacted with furin in vivo, while interactions between furin and its substrates, pro-MT1-MMP and pro-VEGF-C, were decreased by c-Src inhibitors. In conclusion, the interaction among furin and pro-MT1-MMP or pro-VEGF-C or other tumor-associated precursor enzymes can be regulated by c-Src activity, thus reducing or changing the expression of these enzymes in order to reduce the development of gastric cancer, invasion and metastasis. PMID:24841138

Yang, Yun; Bai, Zhi-Gang; Yin, Jie; Wu, Guo-Cong; Zhang, Zhong-Tao

2014-07-01

88

Detailed Measurements of Gastric Electrical Activity and Their Implications on Inverse Solutions  

PubMed Central

Significant research effort has been expended on investigating methods to non-invasively characterize gastrointestinal electrical activity. Despite the clinical success of the 12-lead electrocardiograms (ECG) and the emerging success of inverse methods for characterizing electrical activity of the heart and brain, similar methods have not been successfully transferred to the gastrointestinal field. The normal human stomach generates rhythmic electrical impulses, known as slow waves, that propagate within the stomach at a frequency of 3 cycles per minute. Disturbances in this activity are known to result in disorders in the motility patterns of the stomach. However, there is still limited understanding regarding the basic characteristics of the electrical propagation in the stomach. Contrary to existing beliefs, recent results from high resolution recordings of gastric electrical activity have shown that multiple waves, complete with depolarization and repolarization fronts, can be simultaneously present at any given time in the human stomach. In addition, it has been shown that there are marked variations in the amplitude and velocities in different regions in the stomach. In human recordings, the antrum had slow waves with significantly higher amplitudes and velocities than the corpus. Due to the presence of multiple slow wave events, single and multiple dipole-type inverse methods are not appropriate and distributed source models must therefore be considered. Furthermore, gastric electrical waves move significantly slower than electrical waves in the heart, and it is currently difficult to obtain structural images of the stomach at the same time as surface electrical or magnetic gastric recordings are made. This further complicates the application of inverse procedures for gastric electrical imaging.

Cheng, Leo K.; O'Grady, Greg; Du, Peng; Egbuji, John U.; Windsor, John A.; Pullan, Andrew J.

2014-01-01

89

Role of c-Src activity in the regulation of gastric cancer cell migration  

PubMed Central

Gastric cancer is associated with increased migration and invasion. In the present study, we explored the role of c-Src in gastric cancer cell migration and invasion. BGC-823 gastric cancer cells were used to investigate migration following treatment of these cells with the c-Src inhibitors, PP2 and SU6656. Migration and invasion were analyzed by wound healing and Transwell assays. Western blot analysis was used to detect the expression of MT1-MMP and VEGF-C, while the activity of MMP2 and MMP9 was monitored with gelatin zymography assay. Immunoprecipitation was used to detect interactions among furin, pro-MT1-MMP and pro-VEGF-C. MT1-MMP and VEGF-C expression levels were inhibited by PP2 and SU6656 treatment, in accordance with decreased c-Src activity. Similarly, the zymography assay demonstrated that the activity of MMP2 and MMP9 was decreased following PP2 or SU6656 treatment. Blockade of c-Src also inhibited the invasive and migratory capacity of BGC-823 cells. Notably, c-Src interacted with furin in vivo, while interactions between furin and its substrates, pro-MT1-MMP and pro-VEGF-C, were decreased by c-Src inhibitors. In conclusion, the interaction among furin and pro-MT1-MMP or pro-VEGF-C or other tumor-associated precursor enzymes can be regulated by c-Src activity, thus reducing or changing the expression of these enzymes in order to reduce the development of gastric cancer, invasion and metastasis.

YANG, YUN; BAI, ZHI-GANG; YIN, JIE; WU, GUO-CONG; ZHANG, ZHONG-TAO

2014-01-01

90

Brain-gut interactions between central vagal activation and abdominal surgery to influence gastric myenteric ganglia Fos expression in rats  

PubMed Central

We previously showed that medullary thyrotropin-releasing hormone (TRH) or the stable TRH agonist, RX-77368 administered intracisternally induces vagal-dependent activation of gastric myenteric neurons and prevents post surgery-induced delayed gastric emptying in rats. We investigated whether abdominal surgery alters intracisternal (ic) RX-77368 (50 ng)-induced gastric myenteric neuron activation. Under 10 min enflurane anesthesia, rats underwent an ic injection of saline or RX-77368 followed by a laparotomy and a 1-min cecal palpation, or no surgery and were euthanized 90 min later. Longitudinal muscle/myenteric plexus whole-mount preparations of gastric corpus and antrum were processed for immunohistochemical detection of Fos alone or double labeled with protein gene-product 9.5 (PGP 9.5) and vesicular acetylcholine transporter (VAChT). In the non surgery groups, ic RX-77368 induced a 17 fold increase in Fos-expression in both gastric antrum and corpus myenteric neurons compared to saline injected rats. PGP 9.5 ascertained the neuronal identity of myenteric cells expressing Fos. In the abdominal surgery groups, ic RX-77368 induced a significant increase in Fos-expression in both the corpus and antrum myenteric ganglia compared with ic saline injected rats which has no Fos in the gastric myenteric ganglia. However, the response was reduced by 73–78% compared with that induced by ic RX 77368 without surgery. Abundant VAChT positive nerve fibers were present around Fos positive neurons. These results indicate a bidirectional interaction between central vagal stimulation of gastric myenteric neurons and abdominal surgery. The modulation of gastric vagus-myenteric neuron activity could play an important role in the recovery phase of postoperative gastric ileus.

Miampamba, Marcel; Million, Mulugeta; Tache, Yvette

2011-01-01

91

Multiscale modelling of human gastric electric activity: can the electrogastrogram detect functional electrical uncoupling?  

PubMed

During recent years there has been a growing interest in the assessment of gastric electrical health through cutaneous abdominal recordings. The analysis of such recordings is largely limited to an inspection of frequency dynamics, and this has raised doubts as to whether functional gastric electrical uncoupling can be detected using this technique. We describe here a computational approach to the problem in which the equations governing the underlying physics of the problem have been solved over an anatomically detailed human torso geometry. Cellular electrical activity was embedded within a stomach tissue model, and this was coupled to the torso using an equivalent current source approach. Simulations were performed in which normal and functionally uncoupled (through the introduction of an ectopic antral pacemaker) gastric slow wave activity was present, and corresponding cutaneous electrogastrograms were produced. These were subsequently analysed using the currently recommended techniques, and it was found that the functionally uncoupled situation was indistinguishable from normal slow wave activity using this approach. PMID:16407476

Buist, M L; Cheng, L K; Sanders, K M; Pullan, A J

2006-03-01

92

Transcriptional activation of H+/K+-ATPase genes by gastric GATA binding proteins.  

PubMed

H+/K+-ATPase (composed of alpha and beta subunits) and histamine H2 receptor are specifically expressed in gastric parietal cells. The GATA binding proteins (GATA-GT1 and GATA-GT2, also called GATA-6 and GATA-4, respectively) originally found in the gastric mucosa recognized a sequence motif [gastric motif, (G/C)PuPu(G/C)NGAT(A/T)PuPy] in the upstream regions of the ATPase genes [Tamura, S., Wang, X.-H., Maeda, M., and Futai, M. (1993) Proc. Natl. Acad. Sci. USA 90, 10876-10880]. These proteins activated the transcription of the reporter gene ligated downstream of the control region of the rat ATPase alpha or beta subunit gene but had no effect on the same reporter ligated downstream of the H2 receptor gene. Deletion analyses suggested that the upstream 249 (alpha gene) and 323 (beta gene) base pair sequences from the first letter of the initiation codon are sufficient for activation by the GATA proteins. Interestingly, two and three gastric motifs are located near the TATA-boxes of the alpha and beta genes, respectively. Mutagenesis studies demonstrated that the two motifs proximal to the TATA-box sequences of the ATPase alpha and beta subunit genes were essential for the activation. These results suggest that both the alpha and beta subunit genes are regulated similarly by the GATA binding proteins. The expression system established in this study is a useful system for analyzing the roles of GATA proteins in transcriptional regulation of the H+/K+-ATPase gene. PMID:9192734

Nishi, T; Kubo, K; Hasebe, M; Maeda, M; Futai, M

1997-05-01

93

Activation of P21-activated protein kinase 2 is an independent prognostic predictor for patients with gastric cancer  

PubMed Central

Objective p21-activated kinase (PAK) 2, as a member of the PAK family kinases, is involved in a number of hallmark processes including cell proliferation, survival, mitosis, apoptosis, motility and angiogenesis. However, the clinical significance of the activation of PAK2 in human gastric cancer has not been fully elucidated. The aim of this study was to investigate whether PAK2 expression and its phosphorylation status are correlated with tumor progression and prognosis in gastric cancer. Methods Expression patterns and subcellular localizations of PAK2 and Ser20-phosphorylated PAK2 (pSer20PAK2) in 82 gastric cancer patients were detected by immunohistochemistry. Results Both PAK2 and pSer20PAK2 immunostainings were localized in the cytoplasm of tumor cells of gastric cancer tissues. Compared with the normal gastric mucosa, the expression levels of PAK2 and pSer20PAK2 proteins were both significantly increased (both P?gastric cancer. Conclusion Our data suggest for the first time that PAK2 activation may be associated with advanced tumor progression and poor prognosis of gastric cancer. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1236344107120406.

2014-01-01

94

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase  

PubMed Central

Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.

Alvarez-Suarez, Jose M.; Dekanski, Dragana; Ristic, Slavica; Radonjic, Nevena V.; Petronijevic, Natasa D.; Giampieri, Francesca; Astolfi, Paola; Gonzalez-Paramas, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, Jose L.; Mezzetti, Bruno; Battino, Maurizio

2011-01-01

95

Gastric Expression of Plasminogen Activator Inhibitor (PAI)-1 Is Associated with Hyperphagia and Obesity in Mice  

PubMed Central

The adipokine plasminogen activator inhibitor (PAI)-1 is increased in plasma of obese individuals and exhibits increased expression in the stomachs of individuals infected with Helicobacter. To investigate the relevance of gastric PAI-1, we used 1.1 kb of the H+/K+? subunit promoter to overexpress PAI-1 specifically in mouse gastric parietal cells (PAI-1-H/K? mice). We studied the physiological, biochemical, and behavioral characteristics of these and mice null for PAI-1 or a putative receptor, urokinase plasminogen activator receptor (uPAR). PAI-1-H/K? mice had increased plasma concentrations of PAI-1 and increased body mass, adiposity, and hyperphagia compared with wild-type mice. In the latter, food intake was inhibited by cholecystokinin (CCK)8s, but PAI-1-H/K? mice were insensitive to the satiating effects of CCK8s. PAI-1-H/K? mice also had significantly reduced expression of c-fos in the nucleus tractus solitarius in response to CCK8s and refeeding compared with wild-type mice. Exogenous PAI-1 reversed the effects of CCK8s on food intake and c-fos levels in the nucleus tractus solitarius of wild-type mice, but not uPAR-null mice. Infection of C57BL/6 mice with Helicobacter felis increased gastric abundance of PAI-1 and reduced the satiating effects of CCK8s, whereas the response to CCK8s was maintained in infected PAI-1–null mice. In cultured vagal afferent neurons, PAI-1 inhibited stimulation of neuropeptide Y type 2 receptor (Y2R) expression by CCK8s. Thus, gastric expression of PAI-1 is associated with hyperphagia, moderate obesity, and resistance to the satiating effects of CCK indicating a new role in suppressing signals from the upper gut that inhibit food intake.

Kenny, Susan; Gamble, Joanne; Lyons, Suzanne; Vlatkovic, Nikolina; Dimaline, Rod; Varro, Andrea

2013-01-01

96

Characterization of Gastric Electrical Activity Using Magnetic Field Measurements: A Simulation Study  

PubMed Central

Gastric disorders are often associated with abnormal propagation of gastric electrical activity (GEA). The identification of clinically relevant parameters of GEA using noninvasive measures would therefore be highly beneficial for clinical diagnosis. While magnetogastrograms (MGG) are known to provide a noninvasive representation of GEA, standard methods for their analysis are limited. It has previously been shown in simplistic conditions that the surface current density (SCD) calculated from multichannel MGG measurements provides an estimate of the gastric source location and propagation velocity. We examine the accuracy of this technique using more realistic source models and an anatomically realistic volume conductor model. The results showed that the SCD method was able to resolve the GEA parameters more reliably when the dipole source was located within 100 mm of the sensor. Therefore, the theoretical accuracy of SCD method would be relatively diminished for patients with a larger body habitus, and particularly in those patients with significant truncal obesity. However, many patients with gastric motility disorders are relatively thin due to food intolerance, meaning that the majority of the population of gastric motility patients could benefit from the methods developed here. Large errors resulted when the source was located deep within the body due to the distorting effects of the secondary sources on the magnetic fields. Larger errors also resulted when the dipole was oriented normal to the sensor plane. This was believed to be due to the relatively small contribution of the dipole source when compared to the field produced by the volume conductor. The use of three orthogonal magnetic field components rather than just one component to calculate the SCD yielded marginally more accurate results when using a realistic dipole source. However, this slight increase in accuracy may not warrant the use of more complex vector channels in future superconducting quantum interference device designs. When multiple slow waves were present in the stomach, the SCD map contained only one maximum point corresponding to the more dominant source located in the distal stomach. Parameters corresponding to the slow wave in the proximal stomach were obtained once the dominant slow terminated at the antrum. Additional validation studies are warranted to address the utility of the SCD method to resolve parameters related to gastric slow waves in a clinical setting.

Kim, J. H. K.; Bradshaw, L. A.; Pullan, A. J.; Cheng, L. K.

2010-01-01

97

Ca2+ and Ca2+-activated K+ currents in mammalian gastric smooth muscle cells.  

PubMed

Inward movement of calcium through voltage-dependent channels in muscle is thought to initiate the action potential and trigger contraction. Calcium-activated potassium channels carry large outward potassium currents that may be responsible for membrane repolarization. Calcium and calcium-activated potassium currents were identified in enzymatically isolated mammalian gastric myocytes. These currents were blocked by cadmium and nifedipine but were not substantially affected by diltiazem or D600. No evidence for a tetrodotoxin-sensitive sodium current or an inwardly rectifying potassium current was found. PMID:2409600

Mitra, R; Morad, M

1985-07-19

98

Induction of DMBT1 expression by reduced ERK activity during a gastric mucosa differentiation-like process and its association with human gastric cancer.  

PubMed

Abnormalities in the expression of DMBT1 (deleted in malignant brain tumors 1) have been implicated in the development of esophageal, gastric and colorectal cancers of the alimentary tract, but the underlying mechanism remains unclear. In the present study, using the gastric cell line AGS, we identified two intracellular signaling molecules protein kinase C (PKC) and extracellular signal-related kinase (ERK). They mediated both the phorbol myristate acetate (PMA) downregulation of DMBT1 expression and the initiation of cell differentiation, which was measured by cell cycle withdrawal and the induction of the tissue-specific marker trefoil factor 1 (TFF1). A time-course study showed that following the PMA activation of ERK kinase, the induction of TFF1 and the reduction of DMBT1 were detected at the same time point. We then demonstrated a minimal level of DMBT1 in proliferating AGS cells seeded at low density, where ERK activity was high. Reduction of ERK activity, either by an ERK inhibitor PD98059 or by high-density seeding, significantly reduced AGS cell growth judged by CFSE labeling. This cellular effect was elicited by cyclin D/p21 (Cip/Waf1) and G(0)/G(1) arrest, and was accompanied by a marked increase in DMBT1-expressing cells. Finally, we showed that siRNA directed against DMBT1 had no effect on the induction of a cell growth arrest marker, gut-enriched Kruppel-like factor (GKLF), but reduced the PMA induction of TFF1. Along with its upregulation coinciding with G(0)/G(1) arrest, and its attenuation in differentiated cells, these results suggest that the transient induction of DMBT1 is apparently specific at an early stage of gastric epithelial differentiation-like process, when it may play a role in cell fate decision. Consistent with such a potential function, we detected frequent abnormalities of the DMBT1 expression in the specimens of human gastric adenocarcinoma. PMID:15760920

Kang, Weiqun; Nielsen, Ole; Fenger, Claus; Leslie, Graham; Holmskov, Uffe; Reid, Kenneth B M

2005-06-01

99

Association of Body Mass and Brain Activation during Gastric Distention: Implications for Obesity  

PubMed Central

Background Gastric distention (GD), as it occurs during meal ingestion, signals a full stomach and it is one of the key mechanisms controlling food intake. Previous studies on GD showed lower activation of the amygdala for subjects with higher body mass index (BMI). Since obese subjects have dopaminergic deficits that correlate negatively with BMI and the amygdala is innervated by dopamine neurons, we hypothesized that BMI would correlate negatively with activation not just in the amygdala but also in other dopaminergic brain regions (midbrain and hypothalamus). Methodology/Principal Findings We used functional magnetic resonance imaging (fMRI) to evaluate brain activation during GD in 24 healthy subjects with BMI range of 20–39 kg/m2. Using multiple regression and cross-correlation analyses based on a family-wise error corrected threshold P?=?0.05, we show that during slow GD to maximum volumes of 500 ml and 700 ml subjects with increased BMI had increased activation in cerebellum and left posterior insula, and decreased activation of dopaminergic (amygdala, midbrain, hypothalamus, thalamus) and serotonergic (pons) brain regions and anterior insula, regions that were functionally interconnected with one another. Conclusions The negative correlation between BMI and BOLD responses to gastric distention in dopaminergic (midbrain, hypothalamus, amygdala, thalamus) and serotonergic (pons) brain regions is consistent with disruption of dopaminergic and serotonergic signaling in obesity. In contrast the positive correlation between BMI and BOLD responses in posterior insula and cerebellum suggests an opposing mechanism that promotes food intake in obese subjects that may underlie their ability to consume at once large food volumes despite increasing gastric distention.

Tomasi, Dardo; Wang, Gene-Jack; Wang, Ruiliang; Backus, Walter; Geliebter, Allan; Telang, Frank; Jayne, Millar C.; Wong, Christopher; Fowler, Joanna S.; Volkow, Nora D.

2009-01-01

100

Constitutive activation of gastric H+,K+-ATPase by a single mutation.  

PubMed Central

In the reaction cycle of P-type ATPases, an acid-stable phosphorylated intermediate is formed which is present in an intracellularly located domain of the membrane-bound enzymes. In some of these ATPases, such as Na+,K+-ATPase and gastric H+, K+-ATPase, extracellular K+ ions stimulate the rate of dephosphorylation of this phosphorylated intermediate and so stimulate the ATPase activity. The mechanism by which extracellular K+ ions stimulate the dephosphorylation process is unresolved. Here we show that three mutants of gastric H+,K+-ATPase lacking a negative charge on residue 820, located in transmembrane segment six of the alpha-subunit, have a high SCH 28080-sensitive, but K+-insensitive ATPase activity. This high activity is caused by an increased 'spontaneous' rate of dephosphorylation of the phosphorylated intermediate. A mutant with an aspartic acid instead of a glutamic acid residue in position 820 showed hardly any ATPase activity in the absence of K+, but K+ ions stimulated ATPase activity and the dephosphorylation process. These findings indicate that the negative charge normally present on residue 820 inhibits the dephosphorylation process. K+ ions do not stimulate dephosphorylation of the phosphorylated intermediate directly, but act by neutralizing the inhibitory effect of a negative charge in the membrane.

Swarts, H G; Hermsen, H P; Koenderink, J B; Schuurmans Stekhoven, F M; De Pont, J J

1998-01-01

101

Constitutive activation of gastric H+,K+-ATPase by a single mutation.  

PubMed

In the reaction cycle of P-type ATPases, an acid-stable phosphorylated intermediate is formed which is present in an intracellularly located domain of the membrane-bound enzymes. In some of these ATPases, such as Na+,K+-ATPase and gastric H+, K+-ATPase, extracellular K+ ions stimulate the rate of dephosphorylation of this phosphorylated intermediate and so stimulate the ATPase activity. The mechanism by which extracellular K+ ions stimulate the dephosphorylation process is unresolved. Here we show that three mutants of gastric H+,K+-ATPase lacking a negative charge on residue 820, located in transmembrane segment six of the alpha-subunit, have a high SCH 28080-sensitive, but K+-insensitive ATPase activity. This high activity is caused by an increased 'spontaneous' rate of dephosphorylation of the phosphorylated intermediate. A mutant with an aspartic acid instead of a glutamic acid residue in position 820 showed hardly any ATPase activity in the absence of K+, but K+ ions stimulated ATPase activity and the dephosphorylation process. These findings indicate that the negative charge normally present on residue 820 inhibits the dephosphorylation process. K+ ions do not stimulate dephosphorylation of the phosphorylated intermediate directly, but act by neutralizing the inhibitory effect of a negative charge in the membrane. PMID:9606185

Swarts, H G; Hermsen, H P; Koenderink, J B; Schuurmans Stekhoven, F M; De Pont, J J

1998-06-01

102

Intracellular electrical activity of canine and human gastric smooth muscle.  

PubMed Central

1. Intracellular recordings were obtained from circular smooth muscle fibres of the canine fundus, corpus, antrum and pylorus as well as from the human corpus and antrum. 2. In the canine stomach, all regions of the stomach except the fundus exhibited spontaneous action potentials. 3. The spontaneous action potential consisted of an upstroke potential and a plateau potential. 4. There were regional differences in the configuration of the plateau potential. Corporal and antral smooth muscle did not normally spike during the plateau potential whereas terminal antral and pyloric muscle usually showed spikes on top of the plateau potential. Near the intermediate sphincter, there was a zone of transition in which oscillations in potential of variable amplitude were superimposed on the plateau potential. 5. The configuration of the action potential of the human stomach was similar to the configuration of the canine action potential when the same region of the stomach was compared. 6. The ionic dependence of the plateau potential was studied in canine stomach in an area where neither oscillations nor spikes occurred. 7. In clacium-free solution, all spontaneous activity stopped. D600 selectively suppressed the size of the plateau potential. 8. Sodium-deficient solution reduced the size of the plateau potential. 9. These results suggest that both calcium and sodium may be involved as current carriers in the generation of the plateau potential. Images Fig. 1

el-Sharkawy, T Y; Morgan, K G; Szurszewski, J H

1978-01-01

103

Role of gastric antioxidant and anti-Helicobactor pylori activities in antiulcerogenic activity of plantain banana (Musa sapientum var. paradisiaca).  

PubMed

Studies with plantain banana (Musa sapientum var. paradisiaca) have indicated its ulcer protective and healing activities through its predominant effect on various mucosal defensive factors [Sanyal et.al, Arch Int Pharmacodyn, 149 (1964) 393; 155 (1965) 244]. Oxidative stress and Helicobactorpylori colonization are considered to be important factors in the pathogenesis of gastric ulcers. In the present study methanolic extract of plantain banana pulp (BE) was evaluated for its (i) antiulcer and antioxidant activities in 2 hr cold restraint stress and (ii) anti-H.pylori activity in vitro. The extract (BE, 50 mg/kg, twice daily for 5 days) showed significant antiulcer effect and antioxidant activity in gastric mucosal homogenates, where it reversed the increase in ulcer index, lipid peroxidation and super oxide dismutase values induced by stress. However it did not produce any change in catalase values, which was significantly decreased by stress. Further, in the in vitro study. BE (0.32-1,000 microg/ml) did not show any anti-H.pylori activity. The results suggest absence of anti-H. pyloric activity of methanolic extract of banana in vitro and its antioxidant activity may be involved in its ulcerprotective activity. PMID:12019769

Goel, R K; Sairam, K; Rao, C V

2001-07-01

104

Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants  

PubMed Central

Background & objectives: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. Methods: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg) was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Results: Pretreatment of rats with venlafaxine (40 mg/kg) resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01). Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05). Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05) and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05) on day 7. No significant difference with regard to gastric tolerability was observed among groups. Interpretation & conclusions: Our findings showed significant anti-inflammatory activity of venlafaxine (40 mg/kg) and fluoxetine but these drugs were also associated with an increase in blood pressure. No significant change in mean ulcer index was observed among groups.

Chugh, Preeta Kaur; Kalra, Bhupinder Singh; Kaushik, Nitin; Tekur, Uma

2013-01-01

105

Evaluation of antioxidant and immunity-enhancing activities of Sargassum pallidum aqueous extract in gastric cancer rats.  

PubMed

The effect of Sargassum pallidum (brown seaweed) aqueous extract on the immunity function and antioxidant activities in was studied gastric cancer rats. Treatment with Sargassum pallidum aqueous extract at oral doses 400, 600 or 800 mg/kg body weight was found to provide a dose-dependent protection against N-methyl-N?-nitro-Nnitrosoguanidine (MNNG)-induced immunity damage and oxidative injury by enhancing serum interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) levels, decreasing interleukin-6 (IL-6), interleukin-1? (IL-1?), tumor necrosis factor-alpha (TNF-?) levels, preserving normal antioxidant enzymes activities, and by inhibiting lipid peroxidation in gastric mucosa. It can be concluded that Sargassum pallidum aqueous extract may enhance the immunity and antioxidant activities in gastric cancer rats. PMID:22785269

Zhang, Rui-Li; Luo, Wen-Da; Bi, Tie-Nan; Zhou, Shen-Kang

2012-01-01

106

The Impact of Age, Sex, Body Mass Index and Menstrual Cycle Phase on Gastric Myoelectrical Activity Characteristics in a Healthy Croatian Population  

Microsoft Academic Search

The aim of the study was to determine the impact of demographic and anthropometric parameters on the gastric myoelectrical activity characteristics in a healthy Croatian population. The influence of age, sex, body mass index (BMI) and menstrual cycle phase on the gastric myoelectrical activity characteristics was assessed. The study included 120 healthy subjects of both sexes (60 male and 60

Nikolina Tolj; Dragan Schwarz; Ante Bili; Dragan Jur

107

Helicobacter pylori Infection Stimulates Plasminogen Activator Inhibitor 1 Production by Gastric Epithelial Cells?  

PubMed Central

Chronic infection with the gastric pathogen Helicobacter pylori significantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma. H. pylori strains that possess the cag pathogenicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through which H. pylori upregulates the expression of plasminogen activator inhibitor 1 (PAI-1), a member of the urokinase activator system that is involved in tumor metastasis and angiogenesis. Levels of PAI-1 mRNA and protein were examined in tissues from H. pylori-infected patients and in vitro using AGS gastric epithelial cells. In vitro, cells were infected with toxigenic cag-positive or nontoxigenic cag-negative strains of H. pylori or isogenic mutants. The amount of PAI-1 secretion was measured by enzyme-linked immunosorbent assay, and mRNA levels were determined using real-time PCR. The regulation of PAI-1 was examined using the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor and small interfering RNA. Analysis of human biopsy samples revealed an increase in both PAI-1 mRNA and protein levels in patients with H. pylori gastritis compared to those of uninfected controls. Infection of AGS cells with H. pylori significantly increased PAI-1 mRNA expression and the secretion of PAI-1 protein. Moreover, PAI-1 mRNA and protein production was more pronounced when AGS cells were infected by H. pylori strains carrying a functional cag secretion system than when cells were infected by strains lacking this system. PAI-1 secretion was also reduced when cells were infected with either cagE-negative or cagA-negative mutants. The ectopic overexpression of CagA significantly increased the levels of PAI-1 mRNA and protein, whereas blockade of the ERK1/2 pathway inhibited H. pylori-mediated PAI-1 upregulation. These findings suggest that the upregulation of PAI-1 in H. pylori-infected gastric epithelial cells may contribute to the carcinogenic process.

Keates, A. C.; Tummala, S.; Peek, R. M.; Csizmadia, E.; Kunzli, B.; Becker, K.; Correa, P.; Romero-Gallo, J.; Piazuelo, M. B.; Sheth, S.; Kelly, C. P.; Robson, S. C.; Keates, S.

2008-01-01

108

Effects of electroacupuncture on cardiac and gastric activities in acute myocardial ischemia rats  

PubMed Central

AIM: To observe the effect of electroacupuncture (EA) of “Neiguan” (PC6) and “Gongsun” (SP4) on pathological changes of the heart and stomach in rats with acute myocardial ischemia (AMI), and to explore its underlying mechanism. METHODS: Fifty Wistar rats were randomized into control, model, PC6, SP4 and PC6 + SP4 groups (n = 8 each group). An AMI model was established by occlusion of the descending anterior branch (DAB) of the left coronary artery. ECG-ST of cervico-thoracic lead and electrogastrogram (EGG) were recorded. EA was applied to PC6, SP4 and PC6 + SP4 groups, respectively. At the end of experiments, the rats were transcardically perfused with 4% paraformaldehyde, and the heart base myocardium, gastric antrum and duodenum tissues were sampled, sectioned and stained with a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemical method for displaying nitric oxide synthase (NOS) activity. RESULTS: After AMI, ECG-ST values elevated. After EA, the elevated ECG-ST values at 20 min in PC6 group, at 30 min in PC6 + SP4 and SP4 groups had no significant differences in comparison with their respective basal values before AMI. Following AMI, the amplitude and frequency of slow waves of EGG decreased remarkably (P < 0.05). At 30 min after EA, the mean amplitude and frequency of slow waves of EGG in the three EA groups had no marked differences compared with their individual basal levels and those in the control group. After AMI, the mean integral grey values of NOS-positive product in myocardium, gastric antrum and duodenum tissues in the model group increased remarkably in comparison with the control group, while those in three EA groups were lower than those in the model group. No significant differences were found in ECG-ST and EGG improvement among the three EA groups. However, EA of PC6 had a better effect on ECG-ST and EA of PC4 had a better effect on EGG, respectively. CONCLUSION: EA of PC6, SP4 and PC6 + SP4 can significantly promote the recovery of cardiac and gastric electrical activities after AMI, and up-regulate NOS expression in myocardium, gastric antrum and duodenum tissues.

Wang, Shu-Bin; Chen, Shu-Ping; Gao, Yong-Hui; Luo, Ming-Fu; Liu, Jun-Ling

2008-01-01

109

Mechanism for the inhibition of contractile activity of the gastric antrum and pylorus in rabbits during psychogenic stress.  

PubMed

Psychogenic stress in rabbits (fixation to a frame) was accompanied by the inhibition of contractile activity of the gastric antrum and pylorus. These changes persisted during blockade of muscarinic receptors, nicotinic receptors, alpha(2)-adrenoceptors, and beta(1)/beta(2) adrenoceptors. A stress-induced decrease in gastric motor activity was mediated by the nonadrenergic noncholinergic mechanism. It resulted from the influence of a hormonal stress factor on the stomach, which was probably realized through nonadrenergic inhibitory neurons of the enteric nervous system. PMID:19529847

Berezina, T P; Ovsyannikov, V I

2009-03-01

110

Gastric myoelectrical activity increases after moderate-intensity exercise with no meals under suppressed vagal nerve activity.  

PubMed

Postprandial gastric myoelectrical activity recorded by electrogastrogram (EGG) with the subject in a supine position has shown to be enhanced after moderate-intensity pedaling exercise in an upright seated position, despite the suppression of vagal nerve activity. However, it is still unknown whether the effect is due to the exercise itself and/or a meal or how the position change has influenced the effects. To address this, we used a position-controllable cycle ergometer to examine the effects of the moderate-intensity exercise on EGG activity and the high-frequency (HF) component of heart rate variability (HRV), an index of vagal nerve activity. To eliminate the effect of position change, we carried out the exercise and the EGG recording in the supine position. The peak amplitude of the EGG was enhanced by prior moderate-intensity exercise with a reduced HF component of HRV, which did not differ for postexercise conditions with or without a meal. The small amount of meal itself, however, enhanced both the peak amplitude of the EGG and the HF component of HRV. The peak frequency of EGG was reduced and the instability coefficient of EGG was increased only after the exercise itself. Taken together, these results suggest that the enhanced amplitude of gastric myoelectrical activity can be induced by moderate-intensity exercise itself, even with suppressed vagal nerve activity, and that the mechanism underlying the exercise effects would differ from that underlying the effect of a meal alone. PMID:15541200

Kato, M; Sakai, T; Yabe, K; Miyamura, M; Soya, H

2004-06-01

111

Propeller-based wireless device for active capsular endoscopy in the gastric district.  

PubMed

An innovative approach to active locomotion for capsular endoscopy in the gastric district is reported in this paper. Taking advantage of the ingestion of 500 ml of transparent liquid by the patient, an effective distension of the stomach is safely achieved for a timeframe of approximately 30 minutes. Given such a scenario, an active swallowable capsule able to navigate inside the stomach thanks to a four propeller system has been developed. The capsule is 15 mm in diameter and 30 mm in length, and it is composed of a supporting shell containing a wireless microcontroller, a battery and four motors. The motors enable the rotation of propellers located in the rear side of the device, thus obtaining a reliable locomotion and steering of the capsule in all directions in a liquid. The power consumption has been properly optimized in order to achieve an operative lifetime consistent with the time of the diagnostic inspection of the gastric district, assumed to be no more than 30 minutes. The capsule can be easily remotely controlled by the endoscopist using a joystick together with a purposely developed graphical user interface. The capsule design, prototyping, in vitro, ex vivo and preliminary in vivo tests are described in this work. PMID:19707936

Tortora, Giuseppe; Valdastri, Pietro; Susilo, Ekawahyu; Menciassi, Arianna; Dario, Paolo; Rieber, Fabian; Schurr, Marc Oliver

2009-01-01

112

Comparison and Analysis of Inter-Subject Variability of Simulated Magnetic Activity Generated from Gastric Electrical Activity  

PubMed Central

Electrogastrograms (EGGs) produced from gastric electrical activity (GEA) are used as a non-invasive method to aid in the assessment of a subject’s gastric condition. It has been documented that recordings of the magnetic activity generated from GEA are more reliable. Typically, with magnetic measurements of GEA, only activity perpendicular to the body is recorded. Also, external anatomical landmarks are used to position the magnetic recording devices, SQUIDs, (Superconducting Quantum Interference Devices) over the stomach with no allowance made for body habitus. In the work presented here, GEA and its corresponding magnetic activity are simulated. Using these data, we investigate the effects of using a standard SQUID location as well as a customized SQUID position and the contribution the magnetic component perpendicular to the body makes to the magnetic field. We also explore the effects of the stomach wall thickness on the resultant magnetic fields. The simulated results show that the thicker the wall, the larger the magnitude of the magnetic field holding the same signal patterns. We conclude that most of the magnetic activity arising from GEA occurs in a plane parallel to the anterior body. We also conclude that using a standard SQUID position can be suboptimal.

Komuro, Rie; Cheng, Leo K.; Pullan, Andrew J.

2014-01-01

113

Impaired circadian rhythm of gastric myoelectrical activity in patients with multiple system atrophy.  

PubMed

In order to evaluate gastric motility and its circadian rhythm in patients with multiple system atrophy (MSA) and healthy control subjects, we measured gastric myoelectrical activity (GMA) for 24 hours using a cutaneous electrogastrogram (EGG) recorder in 14 MSA patients and 9 age-matched controls. We analyzed six 10-minute segments of EGG before and after each meal and two 20-minute EGG segments during sleep; three parameters were used for the analysis: dominant frequency (DF), instability coefficient of dominant frequency (ICDF), and dominant power (DP). DF increased during daytime and decreased during sleep in the control, while this circadian variation was blunted in the patients with MSA. The average DF of the eight segments in the MSA patients did not differ from that of the control. Both MSA patients and control subjects did not show the circadian variation of ICDF and DP. The average ICDF of the eight segments in the patients with MSA was significantly decreased when compared with that of the control (p < 0.01). No differences were observed in DP between the two groups. This study indicates that the healthy subjects appear to have a circadian rhythm of DF, and the patients with MSA appear to have impaired circadian rhythm of DF and decreased ICDF possibly due to the degeneration of the central autonomic neurons. PMID:16362538

Suzuki, Atsuya; Asahina, M; Ishikawa, C; Asahina, K M; Honma, K; Fukutake, T; Hattori, T

2005-12-01

114

Expression of the EGF Family in Gastric Cancer: Downregulation of HER4 and Its Activating Ligand NRG4  

PubMed Central

Gastric cancer is a major cause of cancer-related deaths in both men and women. The epidermal growth factor receptors are EGFR, HER2, HER3 and HER4. Of the four epidermal growth factor receptors, EGFR and HER2 are well-known oncogenes involved in gastric cancer. Little, however, is known about the role played by HER3 and HER4 in this disease. We obtained paired samples from the tumor and the adjacent normal tissue from the same patient undergoing surgery for gastric cancer. Using RT-qPCR, we quantified the mRNA expression of the four receptors including the HER4 splicing isoforms and all the ligands activating these receptors. Using immunohistochemistry, the protein expression of HER4 was also quantified. We found that HER2 mRNA expression was upregulated in the tumor tissue compared to the matched normal tissue (p?=?0.0520). All ligands with affinity for EGFR were upregulated, whereas the expression of EGFR was unchanged. Interestingly, we found the mRNA expression of HER4 (p?=?0.0002) and its ligand NRG4 (p?=?0.0009) to be downregulated in the tumor tissue compared to the matched normal tissue. HER4 downregulation was demonstrated for all the alternatively spliced isoforms of this receptor. These results support the involvement of EGFR and HER2 in gastric cancer and suggest an interesting association of reduced HER4 expression with development of gastric cancer.

Nielsen, Trine Ostergaard; Friis-Hansen, Lennart; Poulsen, Steen Seier; Federspiel, Birgitte; Sorensen, Boe Sandahl

2014-01-01

115

Muscarinic activity modulated by C-type natriuretic peptide in gastric smooth muscles of guinea-pig stomach  

Microsoft Academic Search

Natriuretic peptides (NPs) are a cyclic guanosine monophosphate (cGMP) generation system like nitric oxide (NO) and play an inhibitory regulation in gastrointestinal motility but the effect of NPs on muscarinic activity is still unclear. This study was designed to investigate effect of C-type natriuretic peptide (CNP) on muscarinic control of gastric motility and its ion channel mechanism. The spontaneous contraction

De-gang Xing; Xu Huang; Chun-hui Li; Xiang-lan Li; Lian-hua Piao; Ling Gao; Yang Zhang; Yong-chul Kim; Wen-xie Xu

2007-01-01

116

Electrogastrography in adults and children: the strength, pitfalls, and clinical significance of the cutaneous recording of the gastric electrical activity.  

PubMed

Cutaneous electrogastrography (EGG) is a non-invasive technique to record gastric myoelectrical activity from the abdominal surface. Although the recent rapid increase in the development of electrocardiography, EGG still suffers from several limitations. Currently, computer analysis of EGG provides few reliable parameters, such as frequency and the percentage of normal and altered slow wave activity (bradygastria and tachygastria). New EGG hardware and software, along with an appropriate arrangement of abdominal electrodes, could detect the coupling of the gastric slow wave from the EGG. At present, EGG does not diagnose a specific disease, but it puts in evidence stomach motor dysfunctions in different pathological conditions as gastroparesis and functional dyspepsia. Despite the current pitfalls of EGG, a multitasking diagnostic protocol could involve the EGG and the (13)C-breath testing for the evaluation of the gastric emptying time-along with validated gastrointestinal questionnaires and biochemical evaluations of the main gastrointestinal peptides-to identify dyspeptic subgroups. The present review tries to report the state of the art about the pathophysiological background of the gastric electrical activity, the recording and processing methodology of the EGG with particular attention to multichannel recording, and the possible clinical application of the EGG in adult and children. PMID:23762836

Riezzo, Giuseppe; Russo, Francesco; Indrio, Flavia

2013-01-01

117

Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells  

PubMed Central

Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biopsies from subjects with elevated plasma gastrin, the abundances of PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared with subjects with plasma concentrations in the reference range. In patients with hypergastrinemia due to autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1, uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy. Immunohistochemistry revealed localization of PAI-1 to parietal cells and enterochromaffin-like cells in micronodular neuroendocrine tumors in hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI-1-luciferase promoter-reporter construct transfected into AGS-GR cells. There was time- and concentration-dependent increase of PAI-1-luciferase expression in response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways. In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-GR cell migration and invasion, and small interfering RNA treatment increased responses to gastrin. We conclude that elevated plasma gastrin concentrations are associated with increased expression of gastric PAI-1, which may act to restrain gastrin-stimulated cell migration and invasion.

N?rsett, Kristin G.; Steele, Islay; Duval, Cedric; Sammut, Stephen J.; Murugesan, Senthil V. M.; Kenny, Susan; Rainbow, Lucille; Dimaline, Rod; Dockray, Graham J.; Pritchard, D. Mark

2011-01-01

118

Role of ghrelin-induced phosphatidylinositol 3-kinase activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori.  

PubMed

A peptide hormone, ghrelin, is recognized as an important modulator of gastric mucosal inflammatory responses to Helicobacter pylori through the regulation of Src/Akt-dependent activation of constitutive nitric oxide synthase (cNOS) by phosphorylation. In this study, we report on the role of phosphatidylinositol 3-kinase (PI3K) in the processes of Src/Akt activation in gastric mucosal cells exposed to H. pylori LPS. We demonstrate that cNOS activation through phosphorylation induced by ghrelin is associated with PI3K activation which occurs upstream of cSrc, and that PI3K is required for cSrc activation of Akt. We show further that ghrelin-induced activation of PI3K, as well as that of Src and Akt, was susceptible to suppression by the inhibitors of phospholipase C (U73122) and protein kinase C (BIM). Both these inhibitors also blocked the ghrelin-induced membrane translocation of PI3K and cSrc, whereas the inhibitor of PI3K (LY294002) blocked only the membrane translocation of cSrc. Collectively, our findings suggest that the modulatory influence of ghrelin in countering gastric mucosal responses to H. pylori LPS relies on PI3K activation that depends on PLC/PKC signaling pathway, and that PI3K activity is required for the induction of cSrc/Akt activation. PMID:24057979

Slomiany, B L; Slomiany, A

2014-06-01

119

Inhibition of gastric glucosamine synthetase activity by oxygen radicals: a possible cause of decreased mucosal protective capacity.  

PubMed

To clarify the role of oxygen radicals in the mucus metabolism of the gastrointestinal tract, the effect of oxygen radicals on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, was investigated using homogenate derived from rat gastric mucosa. The simultaneous addition of both xanthine and xanthine oxidase caused a significant inhibition of the enzyme activity, and this decrease was counteracted by catalase, but not by superoxide dismutase. Hydrogen peroxide also caused a significant decrease in the enzyme activity; and this effect of hydrogen peroxide was counteracted by catalase and dithiothreitol, but not by mannitol, dimethyl sulfoxide and reduced glutathione. The inhibition of glucosamine synthetase activity by oxygen radicals is considered to be caused by the oxidation of sulfhydryl groups of the enzyme molecule. The present results also suggest that oxygen radicals in the gastrointestinal tract may induce the suppression of a protective mechanism of the gastric mucosa by inhibiting glucosamine synthesis activity. PMID:1405036

Tatsumi, Y; Kodama, T; Kashima, K; Ohkuma, S; Kuriyama, K

1992-04-01

120

Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal-Regulated Kinase 1\\/2 in Human Gastric Cancer Cells  

Microsoft Academic Search

Leptin is known to act as a growth factor through the Janus- activated kinase (JAK)\\/signal transducer and activator of transcription signaling pathway as well as the mitogen- activated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors

Dai Shida; Joji Kitayama; Ken Mori; Toshiaki Watanabe; Hirokazu Nagawa

121

The effect of GR122311X, a bismuth compound with H2-antagonist activity, on 24-hour intragastric acidity.  

PubMed

GR122311X (ranitidine bismuth citrate Glaxo Group Research Ltd) is a bismuth compound with histamine H2-receptor antagonist activity. The gastric acid antisecretory activity of three oral dosage regimens of GR122311X was compared with placebo and 150 mg ranitidine b.d. The median 24-h integrated intragastric acidity was 38, 26 and 18% of the median placebo value during dosing with GR122311X 196, 391 and 782 mg b.d., respectively. The 24-h acid suppression with GR122311X 391 mg b.d. was not significantly different to that produced by 150 mg ranitidine b.d. (24% of placebo acidity). The median 24-h urinary bismuth excretion increased with rising dosage of GR122311X from 19.2 micrograms with 196 mg b.d., to 36.4 micrograms with 391 mg b.d., to 68.7 micrograms with 782 mg b.d. In conclusion, GR122311X is an effective antisecretory agent with modest systemic bismuth absorption. PMID:1686562

Prewett, E J; Nwokolo, C U; Hudson, M; Sawyerr, A M; Fraser, A; Pounder, R E

1991-10-01

122

Helicobacter pylori Infection Stimulates Plasminogen Activator Inhibitor 1 Production by Gastric Epithelial Cells  

Microsoft Academic Search

Chronic infection with the gastric pathogen Helicobacter pylori significantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma. H. pylori strains that possess the cag patho- genicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through which H. pylori upregulates the expression

A. C. Keates; S. Tummala; R. M. Peek Jr; E. Csizmadia; B. Kunzli; K. Becker; P. Correa; J. Romero-Gallo; M. B. Piazuelo; S. Sheth; C. P. Kelly; S. C. Robson; S. Keates

2008-01-01

123

Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects--a correlation study.  

PubMed

We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between the mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between the mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with the application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in the MGG and in mucosal electrodes (r = 0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes. PMID:22735166

Somarajan, S; Muszynski, N D; Obioha, C; Richards, W O; Bradshaw, L A

2012-07-01

124

Targeted inactivation of HDAC2 restores p16INK4a activity and exerts antitumor effects on human gastric cancer.  

PubMed

Aberrant regulation of histone deacetylase 2 (HDAC2) was reported for gastric cancers. However, responsive cancer genes in disease onset and progression are less understood. HDAC2 expression was studied by quantitative RT-PCR and Western blotting. The functional consequences of HDAC2 knockdown on cell-cycle regulation, programmed cell death, and gene target identification was investigated by flow cytometry, Western blotting, electron microscopy, anchorage-independent colony formation, and cell migration assay and by whole-genome microarray. Therapeutic efficacy of HDAC2 knockdown was determined in nude mice with small hairpin expressing human gastric cancer cells. Epigenetic regulation of p16(INK4a) was studied by methylation-specific PCR and chromatin-IP to evidence HDAC2 or acetylated-histone-H4 binding at gene specific promoter sequences. HDAC2 gene and protein expression was significantly upregulated in different histopathologic grades of human gastric cancers and cancer cell lines. HDAC2 inactivation significantly reduced cell motility, cell invasion, clonal expansion, and tumor growth. HDAC2 knockdown-induced G(1)-S cell cycle arrest and restored activity of p16(INK4a) and the proapoptotic factors. This treatment caused PARP cleavage and hypophosphorylation of the Rb-protein, repressed cyclinD1, CDK4, and Bcl-2 expression and induced autophagic phenotype, that is, LC3B-II conversion. Some gastric tumors and cancer cells displayed p16(INK4a) promoter hypermethylation but treatment with 5-aza-deoxycitidine restored activity. With others the methylation status was unchanged. Here, chromatin-IP evidenced HDAC2 binding. Nonetheless, expression of p16(INK4a) was restored by HDAC2 knockdown with notable histone-H4-acetylation, as determined by chromatin-IP. Thus, p16(INK4a) is regulated by HDAC2. HDAC2 is a bona fide target for novel molecular therapies in gastric cancers. PMID:23175521

Kim, Jeong Kyu; Noh, Ji Heon; Eun, Jung Woo; Jung, Kwang Hwa; Bae, Hyun Jin; Shen, Qingyu; Kim, Min Gyu; Chang, Young Gyoon; Kim, Seung-Jin; Park, Won Sang; Lee, Jung Young; Borlak, Jürgen; Nam, Suk Woo

2013-01-01

125

Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach  

PubMed Central

When intracellular recordings were made from the circular layer of the intact muscular wall of the isolated guinea pig gastric corpus, an ongoing regular high frequency discharge of slow waves was detected even though this region lacked myenteric interstitial cells. When slow waves were recorded from preparations consisting of both the antrum and the corpus, slow waves of identical frequency, but with different shapes, were generated in the two regions. Corporal slow waves could be distinguished from antral slow waves by their time courses and amplitudes. Corporal slow waves, like antral slow waves, were abolished by buffering the internal concentration of calcium ions, [Ca2+]i, to low levels, or by caffeine, 2-aminoethoxydiphenyl borate or the chloride channel blocker DIDS. Corporal preparations demonstrated an ongoing discharge of unitary potentials, as has been found in all other tissues containing interstitial cells. The experiments show that the corpus provides the dominant pacemaker activity which entrains activity in other regions of the stomach and it is suggested that this activity is generated by corporal intramuscular interstitial cells.

Hashitani, Hikaru; Garcia-Londono, A Pilar; Hirst, G David S; Edwards, Frank R

2005-01-01

126

AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel.  

PubMed

Paclitaxel (PTX) has shown encouraging activity in the treatment of advanced gastric cancer (GC). However, the fact that more than half of GC patients respond poorly to PTX-based chemotherapies demonstrates the urgent need for biomarkers of PTX sensitivity in GC patients. In the present work, three GC cell lines (BGC-823, HGC-27 and NCI-N87) with different sensitivities to PTX were subjected to DNA microarray analysis. The significantly differentially expressed genes and microRNAs (miRs) were identified and pathway signatures for PTX sensitivity were proposed. Ingenuity Pathway Analysis results showed that the differentially expressed genes were mainly enriched in the ErbB signaling pathway and other pathways. Additionally, the AKT/ERK signaling pathway, which is the pathway downstream of ErbB, was predicted to be active in PTX-resistant GC cell lines. ErbB3 overexpression and AKT/ERK activation in PTX-resistant cell lines were validated, respectively, by quantitative PCR and immunoblotting. Furthermore, 10 miRs were dramatically differently expressed in the three GC cell lines, and a miR-gene network was constructed from these data. Our work uncovered a reliable signature for PTX sensitivity in GC and potential therapeutic targets for GC treatments. PMID:24817940

Wu, Gang; Qin, Xue-Qian; Guo, Jing-Jing; Li, Tian-Yi; Chen, Jin-Hong

2014-01-01

127

AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel  

PubMed Central

Paclitaxel (PTX) has shown encouraging activity in the treatment of advanced gastric cancer (GC). However, the fact that more than half of GC patients respond poorly to PTX-based chemotherapies demonstrates the urgent need for biomarkers of PTX sensitivity in GC patients. In the present work, three GC cell lines (BGC-823, HGC-27 and NCI-N87) with different sensitivities to PTX were subjected to DNA microarray analysis. The significantly differentially expressed genes and microRNAs (miRs) were identified and pathway signatures for PTX sensitivity were proposed. Ingenuity Pathway Analysis results showed that the differentially expressed genes were mainly enriched in the ErbB signaling pathway and other pathways. Additionally, the AKT/ERK signaling pathway, which is the pathway downstream of ErbB, was predicted to be active in PTX-resistant GC cell lines. ErbB3 overexpression and AKT/ERK activation in PTX-resistant cell lines were validated, respectively, by quantitative PCR and immunoblotting. Furthermore, 10 miRs were dramatically differently expressed in the three GC cell lines, and a miR-gene network was constructed from these data. Our work uncovered a reliable signature for PTX sensitivity in GC and potential therapeutic targets for GC treatments.

Wu, Gang; Qin, Xue-Qian; Guo, Jing-Jing; Li, Tian-Yi; Chen, Jin-Hong

2014-01-01

128

NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer  

PubMed Central

The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation.

Murray, D; Horgan, G; MacMathuna, P; Doran, P

2008-01-01

129

Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration  

SciTech Connect

Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca{sup 2+}]{sub i}). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca{sup 2+}]{sub i}, activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system.

Osawa, Hiroyuki [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Ohnishi, Hirohide [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan)]. E-mail: hohnishi@jichi.ac.jp; Takano, Koji [Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Noguti, Takasi [Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Mashima, Hirosato [Department of Gastroenterology, University of Tokyo School of Medicine, Tokyo 113-8655 (Japan); Hoshino, Hiroko [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Kita, Hiroto [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Sato, Kiichi [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Matsui, Hirofumi [Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8576 (Japan); Sugano, Kentaro [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan)

2006-06-02

130

Molecular cloning and expression of rat antisecretory factor and its intracellular localization.  

PubMed

Antisecretory factor (AF) was identified as a pituitary protein that inhibits the intestinal fluid secretion induced by cholera toxin. One aim of this study was to elucidate whether AF is also synthesized in the intestine or if AF produced in the pituitary is transported to the intestinal tract for its function there. cDNA clones encoding a protein proposed to be AF were isolated from rat pituitary gland and intestinal mucosa cDNA libraries. The nucleotide sequences of clones isolated from the rat pituitary gland and intestinal mucosa were identical. The deduced amino acid sequence was highly homologous to the sequence for subunit 5a of the human 26S protease that exists abundantly in the cytosol and nucleus. The production of AF in the intestine was confirmed by Northern blot and immunoblot analyses. Immunocytochemical observations of cells transfected with the rat AF cDNA showed that the AF protein was localized in the cytoplasm. These findings suggest that the protein proposed to be AF may be a cytoplasmic protein, it exists in the intestine rather than being transported from the pituitary gland, and it may function in intestinal cells. PMID:10505793

Tateishi, K; Misumi, Y; Ikehara, Y; Miyasaka, K; Funakoshi, A

1999-01-01

131

Altered bioelectrical and mechanical activities of rat gastric smooth muscle preparations by inhibiting enterocytogenin.  

PubMed

Inhibiting enterocytogenin (IEG), a 4.5 kDa nucleopeptide isolated from pig intestinal mucosa induced dose-dependent alterations in the spontaneous contractile and bioelectric activities of rat gastric smooth muscle when applied at 10(-8) to 10(-4) M. Two separate phases were apparent in the effects observed, an initial contractile phase followed by a relaxation phase. The depolarization and the related contraction were reduced by amiloride and to a lesser extent by nifedipine. This reduction resulted in a corresponding decrease in the magnitude of the subsequent relaxation phase. Charybdotoxin and apamin caused a statistically significant decrease in the hyperpolarization and the magnitude of the relaxation phase and increased the duration of the contractile phase. On a caffeine or noradrenaline background the effects induced by IEG were diminished, suggesting that they are mediated through Ca2+ release from the intracellular Ca2+ stores. We hypothesize that the depolarization induced by IEG involves activation of the voltage-dependent Ca2+ channels with subsequent stimulation of the Ca(2+)-dependent K+ channels and late development of hyperpolarization. PMID:8852814

Trifonov, B B; Kristev, A; Roussev, G K; Kamberov, E S

1996-02-22

132

Anti-invasive Activity of Ethanol Extracts of Ganoderma lucidum through Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activities in Human Gastric Carcinoma Cells  

Microsoft Academic Search

This study investigated the effect of ethanol extracts of Ganoderma lucidum (EGL) on the correlation between tightening of the tight junctions (TJs) and the anti-invasive activity in human gastric adenocarcinoma AGS cells to elucidate further the possible anti-cancer mechanisms that G. lucidum exerts. Within the concentrations of EGL that were not cytotoxic, EGL markedly inhibited the cell motility and invasiveness

Kyung-Jun Jang; In-seok Son; Dong Yeok Shin; Hyun-Min Yoon; Yung Hyun Choi

133

The stimulating effect of ghrelin on gastric motility and firing activity of gastric-distension-sensitive hippocampal neurons and its underlying regulation by the hypothalamus.  

PubMed

Ghrelin is an acylated peptide originally identified in the rat stomach as the endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes gastric motility. Our aims were to explore the effects of ghrelin on gastric-distension-sensitive neurons in the hippocampus and the potential for ghrelin to regulate gastric motility through the arcuate nucleus (Arc). Single-unit discharges in the hippocampus were recorded extracellularly, and gastric motility in conscious rats was monitored. The expression of GHSR-1a in the hippocampus was determined by PCR, Western blot and fluo-immunohistochemistry staining. Retrograde tracing and fluo-immunohistochemistry staining were used to determine ghrelin neuron projection. Ghrelin-Fluoro-Gold double-labelled neurons and GHSR-1a expression were observed in the Arc and hippocampus, respectively. There were gastric-distension-sensitive neurons in the hippocampus that could be excited by ghrelin or by electrical stimulation of the Arc. The excitatory effects could be blocked completely or partly by pretreatment with the ghrelin receptor antagonist [d-Lys-3]-GHRP-6. Gastric motility was significantly promoted by the administration of ghrelin into the hippocampus in a dose-dependent manner that could be completely abolished by [d-Lys-3]-GHRP-6. Electrical stimulation of the Arc could promote gastric motility as well. Nevertheless, these effects could be mitigated by pretreatment with [d-Lys-3]-GHRP-6. Electrical lesioning of the hippocampus diminished the excitatory effects on gastric motility that were induced by electrical stimulation the Arc. Our findings suggest that ghrelin plays an important role in promoting gastric motility via the hippocampus. The Arc may be involved in regulation of the influence of the hippocampus on gastric motility. PMID:24036593

Xu, Luo; Gong, Yanling; Wang, Hongbo; Sun, Xiangrong; Guo, Feifei; Gao, Shengli; Gu, Fang

2014-01-01

134

Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells  

Microsoft Academic Search

BACKGROUND & AIMS: Helicobacter pylori adheres to gastric epithelial cells and stimulates interleukin (IL)-8 production. This may be instrumental in neutrophil infiltration of the gastric epithelium that characterizes H. pylori gastritis. This study examined the molecular mechanisms leading to H. pylori-induced epithelial cell IL-8 production.METHODS: Electrophoretic mobility shift analyses for NF- kappa B were performed on cell and nuclear extracts

S Keates; YS Hitti; M Upton

1997-01-01

135

Gastric culture  

MedlinePLUS

A gastric culture is a test to examine a child's stomach contents for the bacteria that cause tuberculosis . ... This gastric culture can help diagnose lung (pulmonary) tuberculosis in children. This method is used because children cannot cough up and ...

136

Lycopene Enhances Antioxidant Enzyme Activities and Immunity Function in N-Methyl-N?-nitro-N-nitrosoguanidine-Induced Gastric Cancer Rats  

PubMed Central

To investigate anticancer effect of lycopene, we examined the effects of lycopene on the oxidative injury and immunity activities of N-methyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. The animals were divided into five groups. Group I served as the normal control and was given corn oil orally for 20 weeks. Group II were induced with MNNG 200 mg/kg body weight by oral gavage at days 0 and 14, and saturated NaCl (1 mL per rats) was given once every three days for four weeks until the end of the experimental period. Group III, IV and V were posttreated with lycopene (50, 100 and 150 mg/kg body weight, dissolved in corn oil) from the sixth week of MNNG (as in group II) induction up to the end of the experimental period. In the presence of MNNG, MDA and immunity levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) antioxidant activities were decreased in the treated rats compared with normal control rats. Administration of lycopene to gastric carcinoma-induced rats largely up-regulated the redox status and immunity activities to decrease the risk of cancer compared to group II. We conclude that up-regulation of antioxidants and immunity by lycopene treatment might be responsible for the anticancer effect in gastric carcinoma.

Luo, Cong; Wu, Xian-Guo

2011-01-01

137

The carbonyl group of glutamic acid-795 is essential for gastric H+,K+-ATPase activity.  

PubMed

To study the role of Glu795offresent in the fifth transmembrane domain of the alpha-subunit of gastric H+,K+-ATPase, several mutants were generated and expressed in Sf9 insect cells. The E795Q mutant had rather similar properties as the wild-type enzyme. The apparent affinity for K+ in both the ATPase reaction and the dephosphorylation of the phosphorylated intermediate was even slightly enhanced. This indicates that the carbonyl group of Glu795 is sufficient for enzymatic activity. This carbonyl group, however, has to be at a particular position with respect to the other liganding groups, since the E795D and E795N mutants showed a strongly reduced ATPase activity, a lowered apparent K+ affinity, and a decreased steady-state phosphorylation level. In the absence of a carbonyl residue at position 795, the K+ sensitivity was either strongly decreased (E795A) or completely absent (E795L). The mutant E795L, however, showed a SCH 28080 sensitive ATPase activity in the absence of K+, as well as an enhanced spontaneous dephosphorylation rate, that could not be further enhanced by K+, suggesting that this mutant mimicks the filled K+ binding pocket. The results indicate that the Glu795 residue is involved in K+-stimulated ATPase activity and K+-induced dephosphorylation of the phosphorylated intermediate. Glu795 might also be involved in H+ binding during the phosphorylation step, since the mutants E795N, E795D, and E795A showed a decrease in the phosphorylation rate as well as in the apparent ATP affinity in the phosphorylation reaction. This indicates that Glu795 is not only involved in K+ but might also play a role in H+ binding. PMID:10684613

Hermsen, H P; Koenderink, J B; Swarts, H G; De Pont, J J

2000-02-15

138

Effects of cimetidine on adenylate cyclase activity of guinea pig gastric mucosa stimulated by histamine, sodium fluoride and 5'-guanylylimidodiphosphate.  

PubMed

Cimetidine, a recently developed histamine H2-receptor blocking agent has been shown to be a potent inhibitor of histamine-stimulated gastric acid secretion in rat, cat, dog and man. To study the mode of action of cimetidine the modification of stimulatory effects of histamine, sodium flouride and 5'-guanylylimidodiphosphate by cimetidine on the adenylate cyclase activity of guinea pig gastric mucosa was studied. The effect of cimetidine was also compared to that of metiamide, an older histamine H2-receptor antagonist. The effect of cimetidine was qualitatively similar to that of metiamide, i.e. a selective blockade of histamine H2-receptors. Quantitatively cimetidine was about 10-fold more potent than metiamide. PMID:13313

Anttila, P; Westermann, E

1976-08-01

139

KDR-5169, a new gastrointestinal prokinetic agent, enhances gastric contractile and emptying activities in dogs and rats.  

PubMed

KDR-5169, 4-amino-5-chloro-N-[1-(3-fluoro-4-methoxybenzyl)piperidin-4-yl]-2-(2-hydroxyethoxy)benzamide hydrochloride dihydrate, is a new prokinetic with a dual action, i.e., stimulation of the 5-HT4 receptor and antagonism of the dopamine D2 receptor. In this study, we determined in vitro activities of KDR-5169 towards both receptors and demonstrated the effect of the compound on gastrointestinal motor activity in conscious dogs and rats. In dogs, intravenous KDR-5169 stimulated upper gastrointestinal motility in the fasting state and also eliminated the depressive effect of 3,4-dihydroxyphenylalanine (L-DOPA) on this motility in the postprandial state. The effect of KDR-5169 on gastric emptying was further characterized by the use of three rat gastroparesis models (dopamine D2 receptor agonist (quinpirol)-, abdominal surgery-, or combined-situation-induced). Domperidone (a dopamine D2 receptor antagonist) was effective in the quinpirol-delay and combination-delay models, and cisapride and mosapride (5-HT4 receptor agonists) were effective in the surgery-delay model. Only KDR-5169 eliminated the delay of gastric emptying in all three models. In addition, KDR-5169 accelerated emptying to above the normal level in the combination-delay model. These results suggest that KDR-5169 would be effective in various types of gastric ileus caused by different mechanisms. PMID:11779580

Tazawa, Shigeki; Masuda, Naoyuki; Koizumi, Takashi; Kitazawa, Makio; Nakane, Tokio; Miyata, Hiroshi

2002-01-11

140

Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer.  

PubMed

Chlorogenic acid (CGA) is found in many foods, including coffee, berries, potatoes, carrots, wine, apples, and various herbs, and has anti-inflammatory, antidiabetic, and antitumoral actions. The CGA is well absorbed orally, and its effects on gastric ulcer have not been previously reported. The present manuscript evaluated the effect of oral administration of CGA on ethanol/HCl (Et/HCl) or nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer model in male Swiss mice. Animals were pretreated with 0.2 % carboxymethylcellulose (vehicle, p.o.), omeprazole (positive control, 30 mg/kg, p.o.), carbenoxolone (antioxidant positive control, 100 mg/kg, p.o.), or CGA (5, 25, or 50 mg/kg, p.o.). One hour later, the gastric ulcer was induced by injecting Et/HCl solution (100 ?L/10 g body weight; Et 60 %?+?HCl 0.03 M) or piroxicam (100 mg/kg, p.o). After another hour or 4 h later, gastric tissues were collected from Et/HCl or piroxicam-treated animals, respectively, to evaluate the size of the lesion, histological alterations, secretion of gastric acid, neutrophil migration, oxidative/antioxidative enzymes, markers of lipid peroxidation, or concentrations of inflammatory mediators. CGA treatment had a gastroprotective effect in both models, reducing the percentage of lesioned area. CGA treatment did not alter the secretion of gastric action but inhibited neutrophil migration and restored the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione, and thiobarbituric acid reactive substances in mice treated with Et/HCl. Additionally, CGA treatment blocked the increase of tumor necrosis factor alpha and leukotriene B4 but did not restore the reduced prostaglandin levels in the NSAID-induced ulcer. Together, the data presented herein show that CGA may be a suitable natural compound for the prevention and treatment of gastric lesions caused by a different etiology. PMID:23128853

Shimoyama, André T; Santin, José Roberto; Machado, Isabel D; de Oliveira e Silva, Ana Mara; de Melo, Illana L Pereira; Mancini-Filho, Jorge; Farsky, Sandra H P

2013-01-01

141

Heterogeneity in the Activity of Mexican Helicobacter pylori Strains in Gastric Epithelial Cells and Its Association with Diversity in the cagA Gene  

Microsoft Academic Search

Received 12 December 2006\\/Returned for modification 2 February 2007\\/Accepted 9 April 2007 Helicobacter pylori CagA is translocated into gastric epithelial cells by a type IV secretion system and interacts with the Src homology 2 phosphatase, altering cell morphology. Multiple EPIYA motifs in CagA are associated with increased activity in cells and with gastric cancer. The aim of this work was

Adriana Reyes-Leon; John C. Atherton; Richard H. Argent; J. L. Puente; J. Torres

2007-01-01

142

Wnt/?-Catenin Signaling Enhances Cyclooxygenase-2 (COX2) Transcriptional Activity in Gastric Cancer Cells  

PubMed Central

Background Increased expression of the cyclooxygenase-2 enzyme (COX2) is one of the main characteristics of gastric cancer (GC), which is a leading cause of death in the world, particularly in Asia and South America. Although the Wnt/?-catenin signaling pathway has been involved in the transcriptional activation of the COX2 gene, the precise mechanism modulating this response is still unknown. Methodology/Principal Findings Here we studied the transcriptional regulation of the COX2 gene in GC cell lines and assessed whether this phenomenon is modulated by Wnt/?-catenin signaling. We first examined the expression of COX2 mRNA in GC cells and found that there is a differential expression pattern consistent with high levels of nuclear-localized ?-catenin. Pharmacological treatment with either lithium or valproic acid and molecular induction with purified canonical Wnt3a significantly enhanced COX2 mRNA expression in a dose- and time-dependent manner. Serial deletion of a 1.6 Kbp COX2 promoter fragment and gain- or loss-of-function experiments allowed us to identify a minimal Wnt/?-catenin responsive region consisting of 0.8 Kbp of the COX2 promoter (pCOX2-0.8), which showed maximal response in gene-reporter assays. The activity of this pCOX2-0.8 promoter region was further confirmed by site-directed mutagenesis and DNA-protein binding assays. Conclusions/Significance We conclude that the pCOX2-0.8 minimal promoter contains a novel functional T-cell factor/lymphoid enhancer factor (TCF/LEF)-response element (TBE Site II; -689/-684) that responds directly to enhanced Wnt/?-catenin signaling and which may be important for the onset/progression of GC.

Nunez, Felipe; Bravo, Soraya; Cruzat, Fernando; Montecino, Martin; De Ferrari, Giancarlo V.

2011-01-01

143

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.  

PubMed

Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury. PMID:24990304

Sun, Zhaorui; Liu, Hongmei; Yang, Zhizhou; Shao, Danbing; Zhang, Wei; Ren, Yi; Sun, Baodi; Lin, Jinfeng; Xu, Min; Nie, Shinan

2014-09-01

144

PCNA/cyclin defined proliferative activity of epithelial cells in normal gastric mucosa and in chronic gastritis.  

PubMed

Proliferative activity - as measured by the length of proliferation zone and the proliferation index - was studied in 106 gastric biopsies including 27 biopsies with normal mucosa, 53 with chronic superficial gastritis and 26 with chronic atrophic gastritis. Proliferative activity was assessed with PCNA/cyclin monoclonal antibodies and immunohistochemistry in alcohol fixed paraffin embedded sections. Significantly increased mean proliferation index was found in chronic atrophic gastritis as compared with chronic superficial gastritis and normal mucosa. The PCNA/cyclin index that can easily be measured in paraffin embedded sections can be included as an additional criterion to existing histopathologic classifications of gastritis. PMID:8103592

Bielicki, D; Markiewski, M; Marlicz, K; Domaga+a, W

1993-01-01

145

Prevention of Carcinogenesis and Development of Gastric and Colon Cancers by 2-Aminophenoxazine-3-one (Phx-3): Direct and Indirect Anti-Cancer Activity of Phx-3  

PubMed Central

2-Aminophenoxazine-3-one (Phx-3), an oxidative phenoxazine, exerts strong anticancer effects on various cancer cell lines originating from different organs, in vitro. This article reviews new aspects for the prevention of carcinogenesis and development of gastric and colon cancers by Phx-3, based on the strong anticancer effects of Phx-3 on gastric and colon cancer cell lines (direct anticancer effects of Phx-3 for preventing development of cancer), the bacteriocidal effects of Phx-3 against Helicobacter pylori associated with carcinogenesis of gastric cancer (indirect anticancer effects for preventing carcinogenesis of gastric cancer), and the proapoptotic activity of Phx-3 against human neutrophils involved in the incidence of ulcerative colitis associated with a high colon cancer risk (indirect anticancer effects for preventing carcinogenesis of colon cancer).

Tomoda, Akio; Miyazawa, Keisuke; Tabuchi, Takafumi

2013-01-01

146

Dillapiole, isolated from Peperomia pellucida, shows gastroprotector activity against ethanol-induced gastric lesions in Wistar rats.  

PubMed

Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups. PMID:24064453

Rojas-Martínez, Raúl; Arrieta, Jesús; Cruz-Antonio, Leticia; Arrieta-Baez, Daniel; Velázquez-Méndez, Antonio Magdiel; Sánchez-Mendoza, María Elena

2013-01-01

147

Viability and beta-galactosidase activity of dairy propionibacteria subjected to digestion by artificial gastric and intestinal fluids.  

PubMed

An important criterion to consider in the selection of strains for dietary adjuncts is the ability of the microorganisms to survive the severe conditions of acidity and bile concentrations usually found in the gastrointestinal tract. In the present work, we report the effects of digestions by artificial gastric and intestinal fluids on beta-galactosidase activity and survival of four strains of dairy propionibacteria previously selected by their bile tolerance and beta-galactosidase activity. The strains were exposed to artificial gastric juice at pH values between 2 and 7 and then subjected to artificial intestinal digestion. Both viability and beta-galactosidase activity were seriously affected at pH 2. Skim milk and Emmental cheese juice exerted a protective effect on the parameters tested. The trypsin present in the intestinal fluid inactivated the enzyme beta-galactosidase in strains of Propionibacterium freudenreichii but not in Propionibacterium acidipropionici. Moreover, the presence of bile salts enhanced the beta-galactosidase activity of these strains by permeabilization of the cells during the first hour of exposure. The intestinal transit rate confirmed the permanence of the bacteria in the intestine for long enough to be permeabilized. These results suggest that P. acidipropionici would be a good source of beta-galactosidase activity in the intestine. We also propose a practical and effective in vitro method as a tool of screening and selection of potential probiotic bacteria. PMID:10983795

Zárate, G; Chaia, A P; González, S; Oliver, G

2000-09-01

148

Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism.  

PubMed

Cecropia glazioui Sneth (Cecropiaceae) is used in folk medicine in tropical and subtropical Latin America as cardiotonic, diuretic, hypotensive, anti-inflammatory and anti-asthmatic. The hypotensive/antihypertensive activity of the plant aqueous extract (AE) and isolated butanolic fraction (BuF) has been confirmed and putatively related to calcium channels blockade in vascular smooth musculature [Lapa, A.J., Lima-Landman, M.T.R., Cysneiros, R.M, Borges, A.C.R., Souccar, C., Barreta, I.P., Lima, T.C.M., 1999. The Brazilian folk medicine program to validate medicinal plants - a topic in new antihypertensive drug research. In: Hostettman, K., Gupta, M.P., Marston, A. (Eds.), Proceedings Volume, IOCD/CYTED Symposium, Panamá City, Panamá, 23-26 February 1997. Chemistry, Biological and Pharmacological Properties of Medicinal Plants from the Americas. Harwood Academic Publishers, Amsterdam, pp. 185-196; Lima-Landman, M.T., Borges, A.C., Cysneiros, R.M., De Lima, T.C., Souccar, C., Lapa, A.J., 2007. Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. Phytomedicine 14, 314-320]. Bronchodilation and antidepressant-like activities of both AE and BuF have been also shown [Delarcina, S., Lima-Landman, M.T., Souccar, C., Cysneiros, R.M., Tanae, M.M., Lapa, A.J., 2007. Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles. Phytomedicine 14, 328-332; Rocha, F.F., Lima-Landman, M.T., Souccar, C., Tanae, M.M., De Lima, T.C., Lapa, A.J., 2007. Antidepressant-like effect of Cecropia glazioui Sneth and its constituents -in vivo and in vitro characterization of the underlying mechanism. Phytomedicine 14, 396-402]. This study reports the antiulcer and antisecretory gastric acid activities of the plant AE, its BuF and isolated compounds with the possible mechanism involved. Both AE and BuF were assayed on gastric acid secretion of pylorus-ligated mice, on acute models of gastric mucosal lesions, and on rabbit gastric H(+), K(+)-ATPase preparations. Intraduodenal injection of AE or BuF (0.5-2.0g/kg, i.d) produced a dose-related decrease of the basal gastric acid secretion in 4-h pylorus-ligated mice. At 1.0g/kg, BuF decreased the volume (28%) and total acidity (33%) of the basal acid secretion, and reversed the histamine (2.5mg/kg, s.c.)- or bethanecol (1.0mg/kg, s.c.)-induced acid secretion to basal values, indicating inhibition of the gastric proton pump. Pretreatment of mice with the BuF (0.05-0.5g/kg, p.o.) protected against gastric mucosal lesions induced by 75% ethanol, indomethacin (30mg/kg, s.c.) or restraint at 4 degrees C. BuF also decreased the gastric H(+), K(+)-ATPase activity in vitro proportionately to the concentration (IC(50)=58.8microg/ml). The compounds isolated from BuF, consisting mainly of cathechins, procyanidins and flavonoids [Tanae, M.M., Lima-Landman, M.T.R., De Lima, T.C.M., Souccar, C., Lapa, A.J., 2007. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antacid secretion and antidepressant-like activities. Phytomedicine 14, 309-313], inhibited the in vitro gastric H(+), K(+)-ATPase activity at equieffective concentrations to that of BuF. The results indicate that C. glazioui constituents inhibit the gastric proton pump; this effect may account for the effective antisecretory and antiulcer activities of the standardized plant extract. PMID:18462931

Souccar, C; Cysneiros, R M; Tanae, M M; Torres, L M B; Lima-Landman, M T R; Lapa, A J

2008-06-01

149

Nitric oxide synthase activity in rat gastric mucosa contributes to mucin synthesis elicited by calcitonin gene-related peptide.  

PubMed

The majority of research for the calcitonin gene-related peptide (CGRP) in the stomach has been devoted to the submucosal blood flow, and only slight attention has been paid to its involvement in the gastric epithelial function. In this study, we examined the age-related change in the CGRP-containing nerves and its effects on the mucus metabolism. We compared the immunoreactivity for CGRP in the gastric mucosa of 7-week-old rats (young) to that of 52-week-old animals (middle-aged). The effects of CGRP on the mucin biosynthesis were compared using the stomachs from both young and middle-aged rats. The nitric oxide synthase (NOS) activity was measured in the surface and deep mucosa of the gastric corpus. The density of the CGRP nerve fibers was reduced in both the lamina propria and submucosa of the middle-aged rats compared to the young rats. CGRP stimulated the mucin biosynthesis in the cultured corpus mucosa from the 7-week-old rats, but not from the 52-week-old rats. The total NOS activity of the surface layer in the corpus mucosa was markedly reduced in the middle-aged rats compared to the young rats. These findings demonstrate the age-dependent reduction in the CGRP-induced mucin biosynthesis, as well as in the density of the CGRP fibers in the rat stomach. The decreased NOS activity in the surface layer of the oxyntic mucosa in the aged rats may also be a principal cause for the lack of regulation of the mucin biosynthesis by CGRP. PMID:16847357

Ichikawa, Takafumi; Kusakabe, Tatsumi; Gono, Yukari; Shikama, Nobuaki; Hiruma, Hiromi; Kawakami, Tadashi; Ishihara, Kazuhiko

2006-06-01

150

Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress  

PubMed Central

Background This study examined the effects of Palm vitamin E (PVE) and ?-tocopherol (?-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO?+?XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Methods Sixty male Sprague–Dawley rats (200-250?g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or ?-TF at 60?mg/kg body weight. After the treatment period of 28?days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO?+?XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and ?-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and ?-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or ?-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

2012-01-01

151

MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis  

PubMed Central

Background: MicroRNA (miRNA, miR)-18a is a member of the miR-17–92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17–92 cluster and its individual miRNAs are largely unknown. Methods and Results: In this study, we investigated the expression of the miR-17–92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc. Conclusion: Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes.

Wu, W; Takanashi, M; Borjigin, N; Ohno, S-i; Fujita, K; Hoshino, S; Osaka, Y; Tsuchida, A; Kuroda, M

2013-01-01

152

An engineered three-dimensional gastric tumor culture model for evaluating the antitumor activity of immune cells in vitro  

PubMed Central

Monolayer tumor culture models have been used for evaluating the antitumor activity of immune cells in vitro. However, their value in this research is limited. We used human gastric cancer cells (BGC823) and collagen hydrogel as a matrix to establish an engineered three-dimensional (3-D) tumor culture model in vitro. Tumor cells grew in 3-D culture and formed spheroids in the collagen matrix. Evaluation of the antitumor activity of cytokine-induced killer (CIK) cells revealed that, compared with the 2-D cell culture models, CIK cells migrated towards the tumor cells and destroyed the spheroids and tumor cells in the engineered 3-D tumor culture model. The cytotoxicity of CIK cells against the tumor cells in the engineered 3-D tumor culture model was lower than that in 2-D tumor culture models at 12–36 h post-interaction, but there was no significant difference in the cytotoxicity at later time points. Further analysis indicated that dendritic cell-activated CIK cells had a significantly higher level of cytotoxicity against tumor cells, compared with CIK and anti-CEA/CD3-treated CIK cells, in the engineered 3-D tumor culture model. Our data suggest that the engineered 3-D gastric tumor culture model may better mimic the interaction of immune cells with tumor cells in vivo than the 2-D tumor culture models, and may be used for evaluating the antitumor activity of immune cells in vitro.

SUN, PEIMING; XU, YINGXIN; DU, XIAOHUI; NING, NING; SUN, HUIWEI; LIANG, WENTAO; LI, RONG

2013-01-01

153

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells  

SciTech Connect

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF{beta} enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells. Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGF{beta} might be an important pathway of gastric cancer cell proliferation by TGF{beta}.

Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan)] [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

2010-11-19

154

[Total peptic activity in gastric juice and peptic cell mass (chief fundic cells and mucopeptic fundic-antral cells): cellular-secretory correlations in normal subjects].  

PubMed

The aim of this experience has been to evaluate cytosecretory correlations between total peptic activity in gastric juice and gastric peptic cell mass (chief cells and fundic-antral mucopeptic cells) in normal subjects. Gastric peptic cell mass and total peptic activity do not change depending on sex. Concerning age, in spite of a significant decrease of gastric peptic cell mass, peptic activity does not significantly decrease. This apparent disagreement between decreasing anatomic data and functional data, remaining unchanged, may be explained by analyzing the behaviour of fundic and antral peptic cell masses in detail. A difference emerges in the behaviour of chief and mucopeptic cells. The first decrease significantly after 50 years, while the second ones do not show variations, regardless of their fundic and antral location. In particular, fundic mucopeptic cell component increase, but not significantly. The lack of variation in peptic activity in gastric juice after 50 years may be assumed to be connected with the unchanged integrity of mucopeptic cells. PMID:8519857

Testino, G; Cornaggia, M; Cheli, R

1995-09-01

155

Inhibition of gastric H+,K+-ATPase activity by flavonoids, coumarins and xanthones isolated from Mexican medicinal plants.  

PubMed

Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency. The xanthones inhibited the H+,K+-ATPase with IC50 values ranging from 47 microM to 1.6 mM. Coumarins inhibited H+,K+-ATPase with IC50 values of 110 and 638 microM. IC50 values for the flavonoids ranged from 9.6 to 510 microM among which minimiflorin was the most potent. The results suggest that H+,K+-ATPase is sensitive to inhibition by several types of structurally different natural compounds. The potency of the effects on gastric H+,K+-ATPase depends on the presence, position and number of hydroxyls groups in the molecule. Collectively, these results suggest a potential for important pharmacological and toxicological interactions by these types of natural products at the level of H+,K+-ATPase which may explain, at least in part, the gastroprotective properties, indicated by traditional medicine, of the plants from which these compounds were isolated. PMID:16314059

Reyes-Chilpa, Ricardo; Baggio, Cristiane Hatsuko; Alavez-Solano, Dagoberto; Estrada-Muñiz, Elizabeth; Kauffman, Frederick C; Sanchez, Rosa I; Mesia-Vela, Sonia

2006-04-21

156

EGFR and Notch signaling respectively regulate proliferative activity and multiple cell lineage differentiation of Drosophila gastric stem cells.  

PubMed

Quiescent, multipotent gastric stem cells (GSSCs) in the copper cell region of adult Drosophila midgut can produce all epithelial cell lineages found in the region, including acid-secreting copper cells, interstitial cells and enteroendocrine cells, but mechanisms controlling their quiescence and the ternary lineage differentiation are unknown. By using cell ablation or damage-induced regeneration assays combined with cell lineage tracing and genetic analysis, here we demonstrate that Delta (Dl)-expressing cells in the copper cell region are the authentic GSSCs that can self-renew and continuously regenerate the gastric epithelium after a sustained damage. Lineage tracing analysis reveals that the committed GSSC daughter with activated Notch will invariably differentiate into either a copper cell or an interstitial cell, but not the enteroendocrine cell lineage, and loss-of-function and gain-of-function studies revealed that Notch signaling is both necessary and sufficient for copper cell/interstitial cell differentiation. We also demonstrate that elevated epidermal growth factor receptor (EGFR) signaling, which is achieved by the activation of ligand Vein from the surrounding muscle cells and ligand Spitz from progenitor cells, mediates the regenerative proliferation of GSSCs following damage. Taken together, we demonstrate that Dl is a specific marker for Drosophila GSSCs, whose cell cycle status is dependent on the levels of EGFR signaling activity, and the Notch signaling has a central role in controlling cell lineage differentiation from GSSCs by separating copper/interstitial cell lineage from enteroendocrine cell lineage. PMID:24603358

Wang, Chenhui; Guo, Xingting; Xi, Rongwen

2014-05-01

157

A gastric acid secretion model.  

PubMed Central

A theory of gastric acid production and self-protection is formulated mathematically and examined for clinical and experimental correlations, implications, and predictions using analytic and numerical techniques. In our model, gastric acid secretion in the stomach, as represented by an archetypal gastron, consists of two chambers, circulatory and luminal, connected by two different regions of ion exchange. The capillary circulation of the gastric mucosa is arranged in arterial-venous arcades which pass from the gastric glands up to the surface epithelial lining of the lumen; therefore the upstream region of the capillary chamber communicates with oxyntic cells, while the downstream region communicates with epithelial cells. Both cell types abut the gastric lumen. Ion currents across the upstream region are calculated from a steady-state oxyntic cell model with active ion transport, while the downstream ion fluxes are (facilitated) diffusion driven or secondarily active. Water transport is considered iso-osmotic. The steady-state model is solved in closed form for low gastric lumen pH. A wide variety of previously performed static and dynamic experiments on ion and CO2 transport in the gastric lumen and gastric blood supply are for the first time correlated with each other for an (at least) semiquantitative test of current concepts of gastric acid secretion and for the purpose of model verification. Agreement with the data is reported with a few outstanding and instructive exceptions. Model predictions and implications are also discussed. Images FIGURE 1

de Beus, A M; Fabry, T L; Lacker, H M

1993-01-01

158

Activation of command fibres to the stomatogastric ganglion by input from a gastric mill proprioceptor in the crab, Cancer pagurus  

Microsoft Academic Search

In semi?intact preparations of the crab Cancer pagurus the normal output from the stomatogastric ganglion (StG) was a regular pyloric cycle (Figure 4). Repeated stimulation of the posterior stomach nerve (psn) of the posterior gastric mill proprioceptor (PSR) often induced series of spontaneous gastric cycles. We were therefore able to describe the normal gastric cycle as recorded in the output

M. R. Dando; B. Chanussot; F. Nagy

1973-01-01

159

Gastric infarction.  

PubMed

We have described a patient with an acute condition of the abdomen who had infarction of the stomach and the small intestine due to atheromatous thrombus of celiac and superior mesenteric arteries. We believe this unusual simultaneous occurrence of gastric and small intestinal infarction is coincidental. The outcome of gastric infarction is frequently fatal. PMID:2000538

Lin, J I; Park, Y S; Gopalsway, N

1991-03-01

160

Effects of proximal gastric vagotomy (PGV) followed by total vagotomy (TV) on postprandial and fasting myoelectrical activity of the canine stomach and duodenum  

Microsoft Academic Search

Experiments were designed to study the effect of proximal gastric vagotomy (PGV) followed by total vagotomy (TV) on the myoelectrical activity of the canine stomach and duodenum after a meat meal and during fasting. Dogs were prepared with chronically implanted Ag-AgCl-electrodes on the stomach and duodenum. Recordings of electrical activity were made for one hour after the ingestion of a

P Aeberhard; B S Bedi

1977-01-01

161

Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, protects against gastric ischemia–reperfusion damage in rats: role of oxygen free radicals generation  

Microsoft Academic Search

Peroxisome proliferator-activated receptor gamma (PPAR-?) is a nuclear hormone receptor super family that has recently been implicated in atherosclerosis, inflammation, cancer, infertility, and demyelination. Oxidative stress, neutrophil infiltration, proinflammatory cytokines, and the exhibition of luminal acid play a role in the pathogenesis of gastric injury induced by ischemia–reperfusion. Rosiglitazone, a specific PPAR-? ligand, has been shown to have antiinflammatory activity,

Isabel Villegas; Antonio Ramón Martín; Walber Toma; Catalina Alarcón de la Lastra

2004-01-01

162

Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles  

Microsoft Academic Search

The effects of red sap from Croton lechleri (SdD), Euphorbiaceae, on vascular and gastric smooth muscles were investigated. SdD, from 10 to 1000?g\\/ml, induced concentration-dependent vasoconstriction in rat caudal arteries, which was endothelium-independent. In arterial preparations pre-constricted by phenylephrine (0.1?M) or KCl (30mM), SdD also produced concentration-dependent vasoconstriction. To study the mechanisms implicated in this effect we used selective inhibitors

G. Froldi; G. Zagotto; R. Filippini; M. Montopoli; P. Dorigo; L. Caparrotta

2009-01-01

163

Gastric mucosal proliferative and total tyrosine kinases activities increase in Helicobacter pylori -induced chronic gastritis  

Microsoft Academic Search

Background. The intestinal type of gastric cancer is thought to originate from cancer precursor lesions, progressing from H. pylori-induced chronic gastritis, atrophic gastritis, to intestinal metaplasia (IM) and dysplasia. Tyrosine kinases (tyr-k) represent\\u000a the family of proteins that are widely expressed during cell metabolism and are considered as secondary markers for cellular\\u000a proliferation and malignant transformation.\\u000a \\u000a \\u000a Aim of Study. The

Justyna Kotynia; Radzislaw Kordek; Alicja Kozlowska; Ewa Malecka-Panas

2005-01-01

164

Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats  

PubMed Central

Background The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats. Methodology/Principal Findings The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2–6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins. Conclusion/Significance The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax. Key words: ethyl 4-(3, 5-di-ter-butyl-2-hydroxybenzylamino) benzoate; toxicity; antioxidant; gastric-ulcer; anti-ulcer; histology; immunohistochemistry.

Halabi, Mohammed Farouq; Shakir, Raied Mustafa; Bardi, Daleya Abdulaziz; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Hassandarvish, Pouya; Hajrezaie, Maryam; Norazit, Anwar; Abdulla, Mahmood Ameen

2014-01-01

165

Theoretical and computational multiple regression study of gastric electrical activity using dipole tracing from magnetic field measurements.  

PubMed

The biomagnetic inverse problem has captured the interest of both mathematicians and physicists due to its important applications in the medical field. As a result of our experience in analyzing the electrical activity of the gastric smooth muscle, we present here a theoretical model of the magnetic field in the stomach and a computational implementation whereby we demonstrate its realism and usefulness. The computational algorithm developed for this purpose consists of dividing the magnetic field signal input surface into centroid-based grids that allow recursive least-squares approximations to be applied, followed by comparison tests in which the locations of the best-fitting current dipoles are determined. In the second part of the article, we develop a multiple-regression analysis of experimental gastric magnetic data collected using Superconducting QUantum Interference Device (SQUID) magnetometers and successfully processed using our algorithm. As a result of our analysis, we conclude on statistical grounds that it is sufficient to model the electrical activity of the GI tract using only two electric current dipoles in order to account for the magnetic data recorded non-invasively with SQUID magnetometers above the human abdomen. PMID:23345871

Irimia, Andrei; Beauchamp, John J; Bradshaw, L Alan

2004-09-01

166

A comparative study of anti-gastric cancer activity between aqueous extract and ethanol extract of Folium Cordylines Fruticosae.  

PubMed

The active components in Folium Cordylines Fruticosae were extracted by heat reflux method. The solvents used were distilled water and ethanol. The effects of two types of extracts on gastric cancer cells were compared; dry extract yields were calculated, as well as the inhibition rates of gastric cancer MGC-803 cell proliferation and the colony cell counts. The micro-Kjeldahl method was used to measure the cell protein contents and to make a comprehensive comparison. The results showed that the MGC-803 cell inhibition rates of three different concentrations (32.5, 75 and 150 mg/ml) of ethanol extracts increased with the increase of concentration, which was 48.9% at a concentration of 150 mg/ml; aqueous extract of Folium Cordylines Fruticosae had very low inhibitory activity at a low concentration (32.5 mg/ml), which was remained at about 20%. After being affected by two types of extracts, cells had uneven sizes, with very low brightness, while the normal cells presented a uniform full form, with high definition. PMID:24146505

Liu, Shaojun; Cao, Dongbo; Xiao, Zhiming; Liu, Fen; Wang, Xiaoyan; Zhao, Lian; Tian, Li; Shen, Shourong

2013-01-01

167

Omeprazole, a specific inhibitor of gastric (H/sup +/-K/sup +/)-ATPase, is a H/sup +/-activated oxidizing agent of sulfhydryl groups  

SciTech Connect

Omeprazole (5-methoxy-2-(((4-methoxy-3,5- dimethylpyridinyl)methyl)sulfinyl)-1H-benzimidazole) appeared to inhibit gastric (H/sup +/-K/sup +/)-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological reducing agents like cysteine or glutathione, however, were unable to reverse the inhibitory effect of omeprazole. Moreover, acidic environments enhanced the potency of omeprazole. The chemical reactivity of omeprazole with mercaptans is also consistent with the biological action of omeprazole. The N-sulfenylated compound reacted at neutral pH with another stoichiometric amount of ethyl mercaptan to produce omeprazole sulfide quantitatively. The gastric polypeptides of 100 kilodaltons representing (H/sup +/-K/sup +/)-ATPase in the rat gastric mucosa or isolated hog gastric membranes were covalently labeled with (/sup 14/C)omeprazole. The radioactive label bound to the ATPase, however, could not be displaced by mercaptoethanol under the identical conditions where the ATPase activity was fully restored. These observations suggest that the essential sulfhydryl groups which reacted with omeprazole did not form a stable covalent bond with the drug, but rather that they further reacted with adjacent sulfhydryl groups to form disulfides which could be reduced by mercaptoethanol.

Im, W.B.; Sih, J.C.; Blakeman, D.P.; McGrath, J.P.

1985-04-25

168

2-Furoyl-LIGRL-NH2, a potent agonist for proteinase-activated receptor-2, as a gastric mucosal cytoprotective agent in mice  

PubMed Central

Proteinase-activated receptor-2 (PAR2), expressed in capsaicin-sensitive sensory neurons, plays a protective role in gastric mucosa. The present study evaluated gastric mucosal cytoprotective effect of 2-furoyl-LIGRL-NH2, a novel highly potent PAR2 agonist, in ddY mice and in wild-type and PAR2-knockout mice of C57BL/6 background. Gastric mucosal injury was created by oral administration of HCl/ethanol solution in the mice. The native PAR2-activating peptide SLIGRL-NH2, administered intraperitoneally (i.p.) at 0.3–1??mol?kg?1 in combination with amastatin, an aminopeptidase inhibitor, but not alone, revealed gastric mucosal protection in ddY mice, which was abolished by ablation of capsaicin-sensitive sensory neurons. I.p. administration of 2-furoyl-LIGRL-NH2 at 0.1??mol?kg?1, without combined treatment with amastatin, exhibited gastric mucosal cytoprotective activity in ddY mice, the potency being much greater than SLIGRL-NH2 in combination with amastatin. This effect was also inhibited by capsaicin pretreatment. Oral administration of 2-furoyl-LIGRL-NH2 at 0.003–0.03??mol?kg?1 also protected against gastric mucosal lesion in a capsaicin-reversible manner in ddY mice. I.p. 2-furoyl-LIGRL-NH2 at 0.1–0.3??mol?kg?1 caused prompt salivation in anesthetized mice, whereas its oral administration at 0.003–1??mol?kg?1 was incapable of eliciting salivation. In wild-type, but not PAR2-knockout, mice of C57BL/6 background, i.p. administration of 2-furoyl-LIGRL-NH2 caused gastric mucosal protection. Thus, 2-furoyl-LIGRL-NH2 is considered a potent and orally available gastric mucosal protective agent. Our data also substantiate a role for PAR2 in gastric mucosal protection and the selective nature of 2-furoyl-LIGRL-NH2.

Kawabata, Atsufumi; Oono, Yuko; Yonezawa, Daiki; Hiramatsu, Kaori; Inoi, Naoki; Sekiguchi, Fumiko; Honjo, Masami; Hirofuchi, Michiko; Kanke, Toru; Ishiwata, Hiroyuki

2005-01-01

169

Physical Activity and Sedentary Behavior in Relation to Esophageal and Gastric Cancers in the NIH-AARP Cohort  

PubMed Central

Introduction Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). Methods Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI) Results During 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR>5 times/week vs. never=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15–18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR5–6 hrs/day vs. <1 hr=0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. Conclusions We find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior.

Cook, Michael B.; Matthews, Charles E.; Gunja, Munira Z.; Abid, Zaynah; Freedman, Neal D.; Abnet, Christian C.

2013-01-01

170

FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer The article revealed FoxP3 gene function in gastric cancer firstly. Black-Right-Pointing-Pointer Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. Black-Right-Pointing-Pointer Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. Black-Right-Pointing-Pointer Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Black-Right-Pointing-Pointer FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

Ma, Gui-Fen [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China)] [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: shiyao_chen@163.com [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China) [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Sun, Zhi-Rong [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China)] [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China); Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China)] [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Li-Li; Lian, Jing-Jing [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China)] [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Song, Dong-Li [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)] [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)

2013-01-11

171

Gastric carcinogenesis  

PubMed Central

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700?000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates: at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called “intestinal metaplasia”; phenotypic antralization of fundic units, which is called “spasmolytic polypeptide-expressing metaplasia”; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.

Gomceli, Ismail; Demiriz, Baris; Tez, Mesut

2012-01-01

172

Inhibition of NF- ?B activity by minor polar components of extra-virgin olive oil at gastric level.  

PubMed

The present work evaluates the effect of olive oil phenols on NF-?B activity in human gastric adenocarcinoma cells. The total phenol content was measured by the Folin Ciocalteu method, whereas the composition was assessed by LC-MS/MS analysis. Secoiridoids represented 71% and 83% of the Italian and Spanish extracts, respectively, phenol alcohols were in the range 9-13%. Ligustroside aglycone was the most abundant (37% and 46%, respectively, in the Italian and Spanish sample), and the concentration of flavonoids AP and LU was below 1%. Phenol extracts were assayed at 0.25-7.5 µg/mL, whereas single compounds were at 0.5-25 µM. Both the extracts inhibited the NF-?B driven transcription in a concentration-dependent manner: IC(50) for the Italian and the Spanish extract were 0.86 and 1.28 µg/mL, respectively. The IC(50) for individual compounds ranged from 4.5 to 13 µM. All the compounds under study inhibited nuclear translocation as well. The data suggest that consumption of extra-virgin olive oil may be beneficial for preventing the onset of gastric inflammation leading to more serious diseases. PMID:22294468

Sangiovanni, Enrico; Colombo, Elisa; Fumagalli, Marco; Abbiati, Federico; Caruso, Donatella; Dell'Agli, Mario

2012-10-01

173

Glutathione depletion impairs transcriptional activation of heat shock genes in primary cultures of guinea pig gastric mucosal cells.  

PubMed Central

When primary cultures of guinea pig gastric mucosal cells were exposed to heat (43 degree C), ethanol, hydrogen peroxide (H2O2), or diamide, heat shock proteins (HSP90, HSP70, HSP60, and HSC73) were rapidly synthesized. The extent of each HSP induction varied with the type of stress. Ethanol, H2O2, and diamide increased the syntheses of several other undefined proteins besides the HSPs. However, none of these proteins were induced by exposure to heat or the reagents, when intracellular glutathione was depleted to <10% of the control level by pretreatment with DL-buthionine-[S,R]-sulfoximine. Gel mobility shift assay using a synthetic oligonucleotide coding HSP70 heat shock element showed that glutathione depletion inhibited the heat- and the reagent-initiated activation of the heat shock factor 1 (HSF1) and did not promote the expression of HSP70 mRNA. Immunoblot analysis with antiserum against HSF1 demonstrated that the steady-state level of HSF1 was not changed in glutathione-depleted cells, but glutathione depletion inhibited the nuclear translocation of HSF1 after exposure to heat stress. These results suggest that intracellular glutathione may support early and important biochemical events in the acquisition by gastric mucosal cells of an adaptive response to irritants.

Rokutan, K; Hirakawa, T; Teshima, S; Honda, S; Kishi, K

1996-01-01

174

Flavonoid-rich fraction of Maytenus ilicifolia Mart. ex. Reiss protects the gastric mucosa of rodents through inhibition of both H+,K+ -ATPase activity and formation of nitric oxide.  

PubMed

Maytenus ilicifolia Mart. ex. Reissek (Celastraceae), a medicinal plant known in Brazil as "espinheira-santa" is commonly used to treat gastric disorders. The effect of the flavonoid-rich fraction separated from the leaves was evaluated for its gastroprotective properties and the mechanism(s) involved in this activity. Intraperitoneal administration of the flavonoid-rich fraction potently protected rats from experimentally induced chronic (ED(50)=79 mg/kg) and acute gastric lesions by ethanol (ED(50)=25mg/kg) and indomethacin (ED(50)=4 mg/kg) without altering the decreased amount of cytoprotective glutathione and mucus amount in the injured gastric mucosa. A potent reduction of gastric acid hypersecretion (ED(50)=7 mg/kg, i.p.) was accompanied by a reduction of nitric oxide release (ED(50)=1.6 mg/kg, i.p.) in the gastric secretion of 2h pylorus ligated rats which suggests an important role for nitric oxide-dependent mechanisms. Inhibition of gastric acid secretion in vivo was correlated with the in vitro inhibition of rabbit gastric H(+),K(+)-ATPase activity (IC(50)=41 microg/mL). Chemical investigation of the fraction showed galactitol (25%), epicatechin (3.1%) and catechin (2%) as the majoritary components. Collectively, the results show that the flavonoid-rich fraction of Maytenus ilicifolia potently protects animals from gastric lesions with high potency through inhibition of gastric acid secretion. PMID:17706386

Baggio, Cristiane Hatsuko; Freitas, Cristina Setim; Otofuji, Gláucia de Martini; Cipriani, Thales Ricardo; Souza, Lauro Mera de; Sassaki, Guilherme Lanzi; Iacomini, Marcello; Marques, Maria Consuelo Andrade; Mesia-Vela, Sonia

2007-09-25

175

Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat.  

PubMed

The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents. PMID:19453518

Bucinskaite, V; Tolessa, T; Pedersen, J; Rydqvist, B; Zerihun, L; Holst, J J; Hellström, P M

2009-09-01

176

Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats.  

PubMed

Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats. Gastric ulcers were induced by intragastric administration of 75% ethanol. Ghrelin alone or in combination with cyclooxygenase inhibitors was administered twice, 1 and 13 hours after ethanol application. Cyclooxygenase-1 (COX-1) inhibitor (SC-560, 10 mg/kg/dose) or COX-2 inhibitor (celecoxib, 10 mg/kg/dose) were given 30 min prior to ghrelin. Twelve or 24 hours after administration of ethanol, rats were anesthetized and experiments were terminated. The study revealed that administration of ethanol induced gastric ulcers in all animals and this effect was accompanied by the reduction in gastric blood flow and mucosal DNA synthesis. Moreover induction of gastric ulcer by ethanol significantly increased mucosal expression of mRNA for COX-2, IL-1? and TNF-?. Treatment with ghrelin significantly accelerated gastric ulcer healing. Therapeutic effect of ghrelin was associated with significant reversion of the ulcer-evoked decrease in mucosal blood flow and DNA synthesis. Ghrelin administration also caused the reduction in mucosal expression of mRNA for IL-1? and TNF-?. Addition of SC-560 slightly reduced the therapeutic effect of ghrelin in the healing of ethanol-induced ulcer and the ulcer area in rats treated SC-560 plus ghrelin was significantly smaller than that observed in rats treated with saline or SC-560 alone. Pretreatment with celecoxib, a COX-2 inhibitor, abolished therapeutic effect of ghrelin. We concluded that treatment with ghrelin increases healing rate of gastric ulcers evoked by ethanol and this effect is related to improvement in mucosal blood flow, an increase in mucosal cell proliferation, and reduction in mucosal expression of proinflammatory cytokines. Ghrelin is able to reverse a deleterious effect of COX-1 inhibitor on healing of ethanol-induced gastric ulcers. Activity of COX-2 is necessary for the therapeutic effect of ghrelin in healing of ethanol-induced gastric ulcers. PMID:24622834

Warzecha, Z; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Ginter, G; Ptak-Belowska, A; Dembinski, A

2014-02-01

177

Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.  

PubMed

The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing. PMID:22914261

El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

2014-05-01

178

Transforming Growth Factor  Dependent Sequential Activation of Smad, Bim, and Caspase9 Mediates Physiological Apoptosis in Gastric Epithelial Cells  

Microsoft Academic Search

Transforming growth factor (TGF-) has been implicated in the maintenance of homeostasis in various organs, including the gastric epithelium. In particular, TGF--induced signaling was shown to be required for the differentiation-associated physiological apoptosis of gastric epithelial cells, but its mechanism has not been well understood. In this study, the molecular mechanism of TGF--induced apoptosis was analyzed in a human gastric

Masatoshi Ohgushi; Shunsuke Kuroki; Hiroshi Fukamachi; Lorraine A. O'Reilly; Keisuke Kuida; Andreas Strasser; Shin Yonehara

2005-01-01

179

Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice  

PubMed Central

Background The worldwide appearance of drug-resistant strains of H. pylori motivates a search for new agents with therapeutic potential against this family of bacteria that colonizes the stomach, and is associated with adenocarcinoma development. This study was designed to assess in vitro the anti-H. pylori potential of cathelicidin LL-37 peptide, which is naturally present in gastric juice, its optimized synthetic analog WLBU2, and the non-peptide antibacterial agent ceragenin CSA-13. Results In agreement with previous studies, increased expression of hCAP-18/LL-37 was observed in gastric mucosa obtained from H. pylori infected subjects. MBC (minimum bactericidal concentration) values determined in nutrient-containing media range from 100-800 ?g/ml for LL-37, 17.8-142 ?g/ml for WLBU2 and 0.275-8.9 ?g/ml for ceragenin CSA-13. These data indicate substantial, but widely differing antibacterial activities against clinical isolates of H. pylori. After incubation in simulated gastric juice (low pH with presence of pepsin) CSA-13, but not LL-37 or WLBU2, retained antibacterial activity. Compared to LL-37 and WLBU2 peptides, CSA-13 activity was also more resistant to inhibition by isolated host gastric mucins. Conclusion These data indicate that cholic acid-based antimicrobial agents such as CSA-13 resist proteolytic degradation and inhibition by mucin and have potential for treatment of H. pylori infections, including those caused by the clarithromycin and/or metronidazole-resistant strains.

2009-01-01

180

Cisplatin-Induced Gastric Dysrhythmia and Emesis in Dogs and Possible Role of Gastric Electrical Stimulation  

Microsoft Academic Search

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric\\u000a electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric\\u000a serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation\\u000a session,

Xiaoyun Yu; Jie Yang; Xiaohua Hou; Kan Zhang; Wei Qian; J. D. Z. Chen

2009-01-01

181

Anti-invasive activity of ethanol extracts of Ganoderma lucidum through tightening of tight junctions and inhibition of matrix metalloproteinase activities in human gastric carcinoma cells.  

PubMed

This study investigated the effect of ethanol extracts of Ganoderma lucidum (EGL) on the correlation between tightening of the tight junctions (TJs) and the anti-invasive activity in human gastric adenocarcinoma AGS cells to elucidate further the possible anticancer mechanisms that G lucidum exerts. Within the concentrations of EGL that were not cytotoxic, EGL markedly inhibited the cell motility and invasiveness in a concentration-dependent manner. The activities of matrix metalloproteinases (MMP)-2 and MMP-9 in AGS cells were dose-dependently inhibited by treatment with EGL, and this was correlated with a decrease in expression of their mRNA and proteins and the upregulation of the expression of the tissue inhibitors of metalloproteinases. The anti-invasive activity of EGL was also found to be associated with the increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, EGL repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Furthermore, the levels of E-cadherin, a type I transmembrane glycoprotein, were inhibited by EGL treatment, however, those of snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were concentration-dependently increased in response to EGL treatment. Although further studies are needed, the present study indicates that TJs and MMPs are crucial targets of EGL-induced anti-invasiveness in human gastric cancer AGS cells. PMID:22196505

Jang, Kyung-Jun; Son, In-Seok; Shin, Dong Yeok; Yoon, Hyun-Min; Choi, Yung Hyun

2011-12-01

182

Studies on activity of various extracts of Mentha arvensis Linn against drug induced gastric ulcer in mammals  

PubMed Central

AIM: To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid, ethanol and pylorus ligated ulcer models in rats and mice. METHODS: Various crude extracts of petroleum ether, chloroform, or aqueous at a dose of 2 g/kg po did not produce any signs or symptoms of toxicity in treated animals. In the pyloric ligation model oral administration of different extracts such as petroleum ether, chloroform and aqueous at 375 mg/kg po, standard drug ranitidine 60 mg/kg po and control group 1% Tween 80, 5 mL/kg po to separate groups of Wister rats of either sex (n = 6) was performed. Total acidity, ulcer number, scoring, incidence, area, and ulcer index were assessed. RESULTS: There was a decrease in gastric secretion and ulcer index among the treated groups i.e. petroleum ether (53.4%), chloroform (59.2%), aqueous (67.0%) and in standard drug (68.7%) when compared to the negative control. In the 0.6 mol/L HCl induced ulcer model in rats (n = 6) there was a reduction in ulcerative score in animals receiving petroleum ether (50.5%), chloroform (57.4%), aqueous (67.5%) and standard. drug (71.2%) when compared to the negative control. In the case of the 90% ethanol-induced ulceration model (n = 6) in mice, there was a decrease in ulcer score in test groups of petroleum ether (53.11%), chloroform (62.9%), aqueous (65.4%) and standard drug ranitidine (69.7%) when compared to the negative control. It was found that pre-treatment with various extracts of Mentha arvensis Linn in three rat/mice ulcer models ie ibuprofen plus pyloric ligation, 0.6 mol/L HCl and 90% ethanol produced significant action against acid secretion (49.3 ± 0.49 vs 12.0 ± 0.57, P < 0.001). Pre-treatment with various extracts of Mentha arvensis Linn showed highly -significant activity against gastric ulcers (37.1 ± 0.87 vs 12.0 ± 0.57, P < 0.001). CONCLUSION: Various extracts of Mentha arvensis Linn. 375 mg/kg body weight clearly shows a protective effect against acid secretion and gastric ulcers in ibuprofen plus pyloric ligation, 0.6 mol/L HCl induced and 90% ethanol-induced ulcer models.

Londonkar, Ramesh L; Poddar, Pramod V

2009-01-01

183

Modulation of H(+),K(+)-ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells.  

PubMed

ERp57 is a ubiquitous ER chaperone that has disulfide isomerase activity. Here, we found that both ERp57 and gastric H(+),K(+)-ATPase are expressed in a sample derived from the apical canalicular membranes of parietal cells. Overexpression of ERp57 in HEK293 cells stably expressing H(+),K(+)-ATPase significantly increased the ATPase activity without changing the expression level of H(+),K(+)-ATPase. Interestingly, overexpression of a catalytically inactive mutant of ERp57 (C57S/C60S/C406S/C409S) in the cells also increased H(+),K(+)-ATPase activity. In contrast, knockdown of endogenous ERp57 in H(+),K(+)-ATPase-expressing cells significantly decreased ATPase activity without changing the expression level of H(+),K(+)-ATPase. Overexpression and knockdown of ERp57 had no significant effect on the expression and function of Na(+),K(+)-ATPase. These results suggest that ERp57 positively regulates H(+),K(+)-ATPase activity apart from its chaperoning function. PMID:24188822

Fujii, Takuto; Awaka, Shun-Ya; Takahashi, Yuji; Fujita, Kyosuke; Tsuji, Hiroshi; Shimizu, Takahiro; Gomi, Tomoharu; Tsukada, Kazuhiro; Sakai, Hideki

2013-12-11

184

Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA  

PubMed Central

The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20?mg/kg) or tocotrienol (60?mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA.

Kamisah, Yusof; Chua, Kien Hui; Qodriyah, Hj Mohd Saad

2013-01-01

185

Identification of a transforming growth factor beta-1 activator derived from a human gastric cancer cell line.  

PubMed Central

It has been shown that some types of tumour cells produce activated transforming growth factor beta-1 (TGF-beta 1). However, the mechanism for the activation of TGF-beta 1 derived from tumour cells has not been fully elucidated. The present study was undertaken to characterise an activator of latent TGF-beta 1 secreted from a human gastric cancer cell line, KATO-III. Western blot analyses using antibodies for TGF-beta 1, latency associated peptide (LAP) and latent TGF-beta 1-binding protein (LTBP) revealed that, in the cell lysate of KATO-III, TGF-beta 1 protein was expressed as a small latent complex of TGF-beta 1 and LAP. This was also confirmed by a gel chromatographic analysis of the cell lysate obtained from KATO-III. A 2.5 kb transcript of TGF-beta 1 mRNA was detected in KATO-III cells by Northern blot analysis. A gel chromatographic analysis of the conditioned medium from KATO-III cells revealed, in addition to the active form of TGF-beta 1, a factor which activated latent TGF-beta 1 from NRK-49F cells at fractions near a molecular size of 65,000. This factor was inactivated by heat (100 degrees C), acidification, trypsin and serine protease inhibitors. TGF-beta 1 activity in KATO-III cell lysate was not detected in the untreated state, but potent TGF-beta 1 activity was detected after acid treatment. These results suggest that KATO-III releases not only a latent TGF-beta 1 complex but also a type of serine protease, different from plasmin, plasminogen activator, cathepsin D, endoglycosidase F or sialidase, which activates the latent TGF-beta 1 complex as effectively as acid treatment. Images Figure 1

Horimoto, M.; Kato, J.; Takimoto, R.; Terui, T.; Mogi, Y.; Niitsu, Y.

1995-01-01

186

Electrical, contractile, and radiographic studies of the stomach after proximal gastric vagotomy.  

PubMed

The effects of proximal gastric vagotomy on the gastric electrical and contractile activities and on gastric emptying of solid food were studied in dogs. Proximal gastric vagotomy produced only minimal alteration of the electrical activity and did not significantly alter the response of the electrical and contractile activities to vagal stimulation (insulin) and local stimulation (food). Barium meal studies showed no delay in gastric emptying time after proximal gastric vagotomy but significant delay after truncal vagotomy. The findings support the clinical impression that gastric motility and empyting (solid) remain relatively normal after proximal gastric vagotomy. PMID:900334

Rosenquist, C J; Carrigg, J W; Regal, A M; Kohatsu, S

1977-09-01

187

Anti-emetic and emetic effects of erythromycin in Suncus murinus: role of vagal nerve activation, gastric motility stimulation and motilin receptors.  

PubMed

Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 ?M or atropine 1 ?M, facilitated by l-NAME 300 ?M) were facilitated by motilin (1-100 nM) and erythromycin (10-30 ?M). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin. PMID:23201066

Javid, Farideh A; Bulmer, David C; Broad, John; Aziz, Qasim; Dukes, George E; Sanger, Gareth J

2013-01-15

188

14-3-3? attenuates RhoGDI2-induced cisplatin resistance through activation of Erk and p38 in gastric cancer cells  

PubMed Central

Rho GDP dissociation inhibitor 2 (RhoGDI2) promotes tumor growth and malignant progression and enhances chemoresistance of gastric cancer. Recently, we noted an inverse correlation between RhoGDI2 and 14-3-3? expression, which suggests that 14-3-3? is a target of gastric cancer metastasis and the chemoresistance-promoting effect of RhoGDI2. Herein, we evaluated whether 14-3-3? is regulated by RhoGDI2 and is functionally important for the RhoGDI2-induced cisplatin resistance of gastric cancer cells. We used highly metastatic and cisplatin-resistant RhoGDI2-overexpressing SNU-484 cells and observed decreased 14-3-3? mRNA and protein expression. Depletion of 14-3-3? in SNU-484 control cells enhanced cisplatin resistance, whereas restoration of 14-3-3? in RhoGDI2-overexpressing SNU-484 cells impaired cisplatin resistance in vitro and in vivo. We also found that the phosphorylation levels of Erk and p38 kinases significantly decreased in RhoGDI2-overexpressing SNU-484 cells and recovered after 14-3-3? expression, and that decreased activities of these kinases were critical for RhoGDI2-induced cisplatin resistance. In conclusion, 14-3-3? is a RhoGDI2-regulated gene that appears to be important for suppressing the chemoresistance of gastric cancer cells.

Baek, Kyoung Eun; Nam, In-Koo; Park, Seung-Ho; Ryu, Ki-Jun; Ryu, Jinhyun; Choi, Jungil; Hong, Soon-Chan; Kim, Jae Won; Lee, Chang Won; Kang, Sang Soo; Yoo, Jiyun

2013-01-01

189

Multiple G-protein-dependent pathways mediate the antisecretory effects of somatostatin and clonidine in the HT29-19A colonic cell line.  

PubMed Central

Using the functionally differentiated colonic cell line, HT29-19A, we have examined sites at which inhibitory G-proteins mediate the antisecretory actions of somatostatin (SST) and the alpha 2-adrenergic agonist, clonidine (CLON) at the epithelial level. Both agents caused a dose-dependent inhibition (EC50:SST 35 nM; CLON 225 nM) of Cl- secretion (assessed by changes in short circuit current) activated by cAMP-mediated agonists, PGE2 and cholera toxin. Inhibition was accompanied by a reduction in intracellular cAMP accumulation and could be blocked by pretreatment with pertussis toxin at a concentration (200 ng/ml) which activated ADP-ribosylation of a 41-kD inhibitory G protein in HT29-19A membranes. Secretion stimulated by the permeant cAMP analogue, dibutyryl cAMP, was also inhibited by SST and CLON (30-50%; P < 0.005), indicating additional inhibitory sites located distal to cAMP production. Both agents were effective inhibitors of secretion mediated through the Ca2+ signaling pathway. SST (1 microM) and CLON (10 microM) reduced the Isc response to the muscarinic agonist, carbachol, by 60-70%; inhibition was reversed in pertussis toxin-treated cells. These effects did not, however, involve inhibition of the carbachol-induced increase in cellular inositol 1,4,5-trisphosphate levels or the rise in cytosolic calcium, [Ca]i. Inhibition by SST of secretion induced by phorbol 12,13 dibutyrate but not by the calcium agonist, thapsigargin, suggests that SST may act at a distal inhibitory site in the Ca(2+)-dependent secretory process activated by protein kinase C. We conclude that SST and alpha 2-adrenergic agonists can act directly on intestinal epithelial cells to exert a comprehensive inhibition of Cl- secretion mediated through both cAMP and Ca2+/protein kinase C signaling pathways. Inhibition is mediated via pertussis toxin-sensitive G-proteins at sites located both proximal and distal to the production of second messengers. Images

Warhurst, G; Turnberg, L A; Higgs, N B; Tonge, A; Grundy, J; Fogg, K E

1993-01-01

190

Effects of meal size and proximal-distal segmentation on gastric activity  

PubMed Central

AIM: To evaluate the effects of meal size and three segmentations on intragastric distribution of the meal and gastric motility, by scintigraphy. METHODS: Twelve healthy volunteers were randomly assessed, twice, by scintigraphy. The test meal consisted of 60 or 180 mL of yogurt labeled with 64 MBq 99mTc-tin colloid. Anterior and posterior dynamic frames were simultaneously acquired for 18 min and all data were analyzed in MatLab. Three proximal-distal segmentations using regions of interest were adopted for both meals. RESULTS: Intragastric distribution of the meal between the proximal and distal compartments was strongly influenced by the way in which the stomach was divided, showing greater proximal retention after the 180 mL. An important finding was that both dominant frequencies (1 and 3 cpm) were simultaneously recorded in the proximal and distal stomach; however, the power ratio of those dominant frequencies varied in agreement with the segmentation adopted and was independent of the meal size. CONCLUSION: It was possible to simultaneously evaluate the static intragastric distribution and phasic contractility from the same recording using our scintigraphic approach.

Americo, Madileine F; Ietsugu, Marjorie V; Romeiro, Fernando G; Cora, Luciana A; Oliveira, Ricardo B; Miranda, Jose Ricardo A

2010-01-01

191

Gastric cancer cell lines AGS before and after CD40 signal activating.  

PubMed

The aim of this study was to investigate the molecular mechanisms underlying the antitumour effects of CD40L through analysing the change of genes expression profile in AGS using Affymetrix Gene Chip. Human gastric carcinoma AGS cells were first incubated with 2 ?g/ml sCD40L or equal volume of medium (control) in F12 medium. RNA was isolated from AGS and were reverse transcribed, labeled with digoxigenin-11-dUTP, and then hybridized with Clontech Atlas mouse cDNA expression arrays for comparison. Performing clustering analysis, we found that 7 detected genes were down-regulated and 38 were upregulated as the sCD40L acted on AGS. To further verify the results of gene chip screening, Gene Database was searched, finding that the most significantly up-regulated genes were Gadd45a, c-Jun and Bcl-2, and the most significantly down-regulated genes were Cyclin D1, CDC6, TNFR10B, c-IAP2 and ORC5L. Based upon these findings, the signalling pathways that possibly mediate CD40-induced apoptosis are proposed. PMID:22350261

Li, Rui; Pang, Xue-Qin; Chen, Wei-Chang; Li, Ling; Tian, Wen-Yan; Zhang, Xue-Guang

2012-06-01

192

Mimicking of K+ activation by double mutation of glutamate 795 and glutamate 820 of gastric H+,K+-ATPase.  

PubMed

Six double mutants of Glu(795) and Glu(820) present in transmembrane domains 5 and 6 of the alpha-subunit of rat gastric H(+),K(+)-ATPase were generated and expressed with the baculovirus expression system. Five of the six mutants exhibited an SCH 28080-sensitive ATPase activity in the absence of K(+). The activity levels decreased in the following order: E795Q/E820A > E795Q/E820Q > E795Q/E820D congruent with E795A/E820A > E795L/E820Q. The E795L/E820D mutant possessed no constitutive activity. The relative low ATPase activity of the E795L/E820Q mutant is due to its low phosphorylation rate so that the dephosphorylation step was no longer rate-limiting. The constitutively active mutants showed a much lower vanadate sensitivity than the wild-type enzyme and K(+)-sensitive mutants, indicating that these mutants have a preference for the E(1) conformation. In contrast to the constitutively active single mutants generated previously, the double mutants exhibited a high spontaneous dephosphorylation rate at 0 degrees C compared to that of the wild-type enzyme. In addition, the H(+),K(+)-ATPase inhibitor SCH 28080 increased the steady-state phosphorylation level of the constitutively active mutants, due to the formation of a stable complex with the E(2)-P form. These studies further substantiate the idea that the empty ion binding pockets of some mutants apparently mimic the K(+)-filled binding pocket of the native enzyme. PMID:11371216

Hermsen, H P; Swarts, H G; Wassink, L; Koenderink, J B; Willems, P H; De Pont, J J

2001-05-29

193

All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to lymphokine-activated killer cytotoxicity.  

PubMed Central

All-trans retinoic acid (RA) was previously shown to regulate the growth of gastric cancer cells derived from the cell line SC-M1. This study was designed to investigate the effect of RA on the sensitivity of SC-M1 cells to lymphokine-activated killer (LAK) activity. RA at the concentration range of 0.001-10 microM was shown to induce SC-M1 cells to exhibit resistance to LAK activity in a dose-dependent manner. A kinetics study indicated that a significantly increased resistance was detected after 2 days of co-culturing SC-M1 cells with RA and reached a maximum after 6 days of culture. Similar results were obtained from two other cancer cell lines: promyelocytic leukaemia HL-60 and hepatic cancer Hep 3B. A binding assay demonstrated that the binding efficacy between target SC-M1 cells and effector LAK cells was not altered by RA. Flow cytometric analyses revealed that RA exhibited no effect on the expression of cell surface molecules, including HLA class I and class II antigens, intercellular adhesion molecule-1 and -2, and lymphocyte function antigen-3. Cell cycle analysis revealed that culture of SC-M1 cells with RA resulted in an increase in G0/G1 phase and a decrease in S phase, accompanied by a decrease in cyclin A and cyclin B1 mRNA as determined by Northern blot analysis. Additionally, RA was shown to enhance the expression of retinoic acid receptor alpha (RAR alpha) in SC-M1 cells, and to have no effect on the expression of RARbeta or RARgamma. Taken together, these results indicate that RA can significantly increase gastric cancer cells SC-M1 to resist LAK cytotoxicity by means of a cytostatic effect through a mechanism relating to cell cycle regulation. The prevailing ideas, such as a decrease in effector to target cell binding, a reduced MHC class I antigen expression or an altered RARbeta expression, are not involved. Images Figure 4 Figure 5

Chao, T. Y.; Jiang, S. Y.; Shyu, R. Y.; Yeh, M. Y.; Chu, T. M.

1997-01-01

194

Gastric lipoma  

PubMed Central

We report a 12-year-old-boy with gastric lipoma. Upper gastrointestinal (GI) endoscopy with biopsy and abdominal computed tomogram (CT) scan revealed the diagnosis. Open surgical excision of the mass with stomach preservation was done. The clinical presentation and management are discussed and the literature reviewed here. This is the sixth pediatric case reported in the English literature.

Zameer, M.; Kanojia, R. P.; Rao, K. L. N.; Menon, P.; Samujh, R.; Thapa, B. R.

2010-01-01

195

Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NF?B signaling pathway in gastric cancer cells  

PubMed Central

Background Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Results Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-?B in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-?B-DNA-binding activity. Conclusions Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-?B may explain a new role of resistin in the link of obesity and gastric cancer.

2014-01-01

196

Rhizoma Pinelliae trypsin inhibitor separation, purification and inhibitory activity on the proliferation of BGC-823 gastric adenocarcinoma cells  

PubMed Central

The aim of this study was to isolate and purify Rhizoma Pinelliae trypsin inhibitor (RPTI), determine its N-terminal amino acid sequence and evaluate its inhibitory effect on the proliferation of poorly differentiated BGC-823 human gastric adenocarcinoma cells. RPTI was separated and purified from a 40% (NH4)2SO4 precipitate of crude protein extract of Pinellia ternata tuber using affinity chromatography with trypsin as the ligand. The N-terminal amino acid sequence of RPTI was determined using the Edman degradation method. The inhibitory effect of RPTI on BGC-823 cell proliferation was detected in vitro using the MTT method and in vivo in tumour-bearing mice. The purified RPTI showed a single band under SDS-PAGE, its molecular weight was 14 kDa and its N-terminal amino acid sequence was DPVVDG. RPTI inhibited trypsin activity, with an inhibition ratio of 1:6.78 (mass). RPTI significantly inhibited the proliferation of BGC-823 cells in vitro. The IC50 of RPTI was 16.96 ?g/ml within 48 h after treatment and 9.61 ?g/ml within 72 h after treatment. Subcutaneous injection of RPTI around the tumour significantly inhibited BGC-823 tumour growth in mice. The tumour inhibitory effect was concentration- and dose-dependent. RPTI did not significantly influence the spleen coefficient of the mice. In conclusion, RPTI is a serine proteinase inhibitor with antitumour activity.

ZU, GUOHONG; WANG, HOUWEI; WANG, JIE; DOU, YAN; ZHAO, WEICHONG; SUN, YUPING

2014-01-01

197

Apoptotic effect of Epigallocatechin-3-gallate on the human gastric cancer cell line MKN45 via activation of the mitochondrial pathway  

Microsoft Academic Search

AIM: To investigate whether Epigallocatechin-3-gallate (EGCG) can induce apoptosis of the gastric cancer cell line MKN45 and its apoptotic pathway. METHODS: To determine this, apoptotic rates of MKN45 cells after EGCG treatment with or without caspase-3 inhibitor were evaluated by Annexin V-FITC + PI staining The influence of EGCG on the activity of caspase-3 in the MKN45 cells was determined

Zhi-Hua Ran; Qi Xu; Jin-Lu Tong; Shu-Dong Xiao

2007-01-01

198

Salivary amylase activity is useful for assessing perioperative stress in response to pain in patients undergoing endoscopic submucosal dissection of gastric tumors under deep sedation  

Microsoft Academic Search

Background  Although endoscopic submucosal dissection (ESD) for patients with gastric tumors under the conditions of unconsciousness is\\u000a considered to be minimally invasive, no objective assessment of the perioperative stress of ESD has yet been conducted. Today,\\u000a stress levels can be easily and objectively assessed by monitoring salivary amylase activity (sAMY). We evaluated the perioperative\\u000a changes in the sAMY in patients undergoing

Masaya Uesato; Yoshihiro Nabeya; Takashi Akai; Masahito Inoue; Yoshiyuki Watanabe; Hiroshi Kawahira; Toshitaka Mamiya; Yoshihito Ohta; Ryuji Motojima; Akiko Kagaya; Yorihiko Muto; Hideki Hayashi; Hisahiro Matsubara

2010-01-01

199

Role of calcium mobilization in sodium nitroprusside- induced increase of calcium-activated potassium currents in gastric antral circular myocytes of guinea pig1  

Microsoft Academic Search

AIM: To investigate the role of calcium mobilization in the calcium-activated potassium currents (IK(Ca)) increased by sodium nitroprusside (SNP), a nitric oxide (NO) donor, in gastric antral circular myocytes of the guinea pig. METHODS: A perforated patch-clamp technique was used, and the myocytes were isolated by collagenase. RESULTS: SNP 100 µmol\\/L significantly increased IK(Ca), and enhanced the spontaneous transient outward

YU Yong-Chun; GUO Hui-Shu; LI Ying; PIAO Lin; LI Lin; LI Zai-Liu; XU Wen-Xie

200

Bovine ?-Lactalbumin Stimulates Mucus Metabolism in Gastric Mucosa  

Microsoft Academic Search

Bovine ?-lactalbumin (?-LA), a major milk protein, exerts strong gastroprotective activity against rat ex- perimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of ?-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were se- lected

Y. Ushida; Y. Shimokawa; T. Toida; H. Matsui; M. Takase

2007-01-01

201

Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue.  

PubMed Central

1. The biological activities of the proteinase-activated receptor number 2 (PAR-2)-derived peptides, SLIGRL (PP6) SLIGRL-NH2 (PP6-NH2) and SLIGR-NH2 (PP5-NH2) were measured in mouse and rat gastric longitudinal muscle (LM) tissue and in a rat aortic ring preparation and the actions of the PAR-2-derived peptides were compared with trypsin and with the actions of the thrombin receptor activating peptide, SFLLR-NH2 (TP5-NH2). 2. From a neonatal rat intestinal cDNA library, and from intestinal and kidney-derived cDNA, the coding region of the rat PAR-2 receptor was cloned and sequenced, thereby establishing its close sequence identity with the previously described mouse PAR-2 receptor; and this information, along with a reverse-transcriptase (RT) polymerase chain reaction (PCR) analysis of cDNA derived from gastric and aortic tissue was used to establish the concurrent presence of PAR-2 and thrombin receptor mRNA in both tissues. 3. In the mouse and rat gastric preparations, the PAR-2-derived polypeptides, PP6, PP6-HN2 and PP5-NH2 caused contractile responses that mimicked the contractile actions of low concentrations of trypsin (5 u/ml-1; 10 nM) and that were equivalent to contractions caused by TP5-NH2. 4. The cumulative exposure of the rat LM tissue to PP6-NH2 led to a desensitization of the contractile response to this polypeptide, but not to TP5-NH2 and vice versa, so as to indicate a lack of cross-desensitization between the receptors responsive to the PAR-2 and thrombin receptor-derived peptides. 5. In the rat gastric preparation, the potencies of the PAR-2-activating peptides were lower than the potency of TP5-NH2 (potency order: TP5-NH2 > > PP6-NH2 > or = PP6 > PP5-NH2); PP6 was a partial agonist in this preparation. 6. The contractile actions of PP6 and PP6-NH2 in the rat gastric preparation required the presence of extracellular calcium, were inhibited by nifedipine and were blocked by the cyclo-oxygenase inhibitor, indomethacin and by the tyrosine kinase inhibitor, genistein, but not by the kinase C inhibitor, GF109203X. The contractile responses were not blocked by atropine, chlorpheniramine, phenoxybenzamine, propranolol, ritanserin or tetrodotoxin. 7. In a precontracted rat aortic ring preparation, with an intact endothelium, all of the PAR-2-derived peptides caused a prompt relaxation response that was blocked by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME) but not by D-NAME; in an endothelium-free preparation, which possessed mRNA for both the PAR-2 and thrombin receptors, the PAR-2-activating peptides caused neither a relaxation nor a contraction, in contrast with the contractile action of TP5-NH2. The relaxation response to PP6-NH2 was not blocked by atropine, chlorpheniramine, genistein, indomethacin, propranolol or ritanserin. 8. In the rat aortic preparation, the potencies of PP6, PP6-NH2 and PP5-NH2 were greater than those of the thrombin receptor activating peptide, TP5-NH2 (potency order: PP6-NH2 > or = PP6 > PP5-NH2 > TP5-NH2). 9. In the rat aortic preparation, the relaxant actions of the PAR-2-derived peptides were mimicked by trypsin, at concentrations (0.5-1 u ml-1; 1-2 nM) lower than those that can activate the thrombin receptor. 10. The bioassay data obtained with the PAR-2 peptides and with trypsin, along with the molecular cloning/RT-PCR analysis, point to the presence of functional PAR-2 receptors that can activate distinct responses in the gastric and vascular smooth muscle preparations. These responses were comparable to those resulting from thrombin receptor activation in the same tissues, so as to suggest that the receptor for the PAR-2-activating peptides may play a physiological role as far reaching as the one proposed for the thrombin receptor. Images Figure 7

Saifeddine, M.; al-Ani, B.; Cheng, C. H.; Wang, L.; Hollenberg, M. D.

1996-01-01

202

CD49f(high) cells retain sphere-forming and tumor-initiating activities in human gastric tumors.  

PubMed

Identification of gastric tumor-initiating cells (TICs) is essential to explore new therapies for gastric cancer patients. There are reports that gastric TICs can be identified using the cell surface marker CD44 and that they form floating spheres in culture, but we could not obtain consistent results with our patient-derived tumor xenograft (PDTX) cells. We thus searched for another marker for gastric TICs, and found that CD49f(high) cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49f(low) cells did not when subcutaneously injected into immunodeficient mice. These results indicate that CD49f, a subunit of laminin receptors, is a promising marker for human gastric TICs. We established a primary culture system for PDTX cells where only CD49f(high) cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49f(high) sphere cells formed tumors with histological features of parental ones, indicating that only TICs could grow in the culture system. Using this system, we found that some sphere-forming TICs were more resistant than gastric tumor cell lines to chemotherapeutic agents, including doxorubicin, 5-fluorouracil and doxifluridine. There was a patient-dependent difference in the tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs. These results suggest that ECM plays an essential role for the growth of TICs, and that this culture system will be useful to find new drugs targeting gastric TICs. PMID:24015244

Fukamachi, Hiroshi; Seol, Hyang Sook; Shimada, Shu; Funasaka, Chikako; Baba, Kanako; Kim, Ji Hun; Park, Young Soo; Kim, Mi Jeung; Kato, Keiji; Inokuchi, Mikito; Kawachi, Hiroshi; Yook, Jeong Hwan; Eishi, Yoshinobu; Kojima, Kazuyuki; Kim, Woo Ho; Jang, Se Jin; Yuasa, Yasuhito

2013-01-01

203

I. Effect of acetylsalicylic acid upon gastric activity and the modifying action of calcium gluconate and sodium bicarbonate  

Microsoft Academic Search

Conclusions  1. In some normal human subjects and normal dogs, single oral doses (1–2 gms.) of acetylsalicylic acid caused gastric retention;\\u000a the addition of calcium gluconate tended to increase the degree of retention while the addition of sodium bicarbonate increased\\u000a the rate of gastric evacuation.\\u000a \\u000a 2. In normal human subjects and normal dogs, single oral doses of acetylsalicylic acid increased the

J. G. Schnedorf; W. B. Bradley; A. C. Ivy

1936-01-01

204

CD49fhigh Cells Retain Sphere-Forming and Tumor-Initiating Activities in Human Gastric Tumors  

PubMed Central

Identification of gastric tumor-initiating cells (TICs) is essential to explore new therapies for gastric cancer patients. There are reports that gastric TICs can be identified using the cell surface marker CD44 and that they form floating spheres in culture, but we could not obtain consistent results with our patient-derived tumor xenograft (PDTX) cells. We thus searched for another marker for gastric TICs, and found that CD49fhigh cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49flow cells did not when subcutaneously injected into immunodeficient mice. These results indicate that CD49f, a subunit of laminin receptors, is a promising marker for human gastric TICs. We established a primary culture system for PDTX cells where only CD49fhigh cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49fhigh sphere cells formed tumors with histological features of parental ones, indicating that only TICs could grow in the culture system. Using this system, we found that some sphere-forming TICs were more resistant than gastric tumor cell lines to chemotherapeutic agents, including doxorubicin, 5-fluorouracil and doxifluridine. There was a patient-dependent difference in the tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs. These results suggest that ECM plays an essential role for the growth of TICs, and that this culture system will be useful to find new drugs targeting gastric TICs.

Fukamachi, Hiroshi; Seol, Hyang Sook; Shimada, Shu; Funasaka, Chikako; Baba, Kanako; Kim, Ji Hun; Park, Young Soo; Kim, Mi Jeung; Kato, Keiji; Inokuchi, Mikito; Kawachi, Hiroshi; Yook, Jeong Hwan; Eishi, Yoshinobu; Kojima, Kazuyuki; Kim, Woo Ho; Jang, Se Jin; Yuasa, Yasuhito

2013-01-01

205

Preventive activity of pyrrolizidine alkaloids from Senecio brasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats  

Microsoft Academic Search

The alkaloid extract of Senecio brasiliensis inflorescences contain a mixture of the pyrrolizidine alkaloids (PA) senecionine, integerrimine, retrorsine, usaramine and seneciphylline. We evaluated this PA mixture on preventive antiulcerogenic effects on standard rodent models of induced gastric and duodenal ulcers. In the HCl\\/ethanol, indomethacin–bethanechol and hypothermic-restraint-induced gastric ulcer, the lesion was significantly inhibited by PA (p.o.) (p < 0.001). In

Walber Toma; José Roberto Trigo; Ana Cláudia Bensuaski de Paula; Alba Regina Monteiro Souza Brito

2004-01-01

206

Inhibiting Enhancer of Zeste Homolog 2 Promotes Cellular Senescence in Gastric Cancer Cells SGC-7901 by Activation of p21 and p16.  

PubMed

Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Enhancer of zeste homolog 2 (EZH2) as a member of polycomb group proteins and its targets include cell cycle regulatory proteins, which govern cell cycle progression and cellular senescence. In this study, we report that EZH2 depletion promotes the senescent state in human gastric cancer cells SGC-7901. We found that EZH2 functionally suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2 depletion inhibited cell proliferation, arrested cellular cycle, restored features of a cellular senescence phenotype, and promoted doxorubicin-induced senescence. To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent manner. Taken together, our data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16, and could serve as a potential epigenetic target for gastric cancer therapy. PMID:24588771

Bai, Jie; Chen, Junhua; Ma, Muyuan; Cai, Ming; Xu, Fei; Wang, Guobin; Tao, Kaixiong; Shuai, Xiaoming

2014-06-01

207

Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell proliferation in gastric mucosa during the healing process.  

PubMed

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases. PMID:22969019

Pereira, Isabela Tiemy; Burci, Lígia Moura; da Silva, Luisa Mota; Baggio, Cristiane Hatsuko; Heller, Melina; Micke, Gustavo Amadeu; Pizzolatti, Moacir Geraldo; Marques, Maria Consuelo Andrade; Werner, Maria Fernanda de Paula

2013-07-01

208

Non-coding RNAs and gastric cancer  

PubMed Central

Non-coding RNAs (ncRNAs) play key roles in development, proliferation, differentiation and apoptosis. Altered ncRNA expression is associated with gastric cancer occurrence, invasion, and metastasis. Moreover, aberrant expression of microRNAs (miRNAs) is significantly related to gastric cancer tumor stage, size, differentiation and metastasis. MiRNAs interrupt cellular signaling pathways, inhibit the activity of tumor suppressor genes, and affect the cell cycle in gastric cancer cells. Some miRNAs, including miR-21, miR-106a and miR-421, could be potential markers for the diagnosis of gastric cancer. Long non-coding RNAs (lncRNAs), a new research hotspot among cancer-associated ncRNAs, play important roles in epigenetic, transcriptional and post-transcriptional regulation. Several gastric cancer-associated lncRNAs, such as CCAT1, GACAT1, H19, and SUMO1P3, have been explored. In addition, Piwi-interacting RNAs, another type of small ncRNA that is recognized by gastroenterologists, are involved in gastric carcinogenesis, and piR-651/823 represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice. Small interfering RNAs also function in post-transcriptional regulation in gastric cancer and might be useful in gastric cancer treatment.

Li, Pei-Fei; Chen, Sheng-Can; Xia, Tian; Jiang, Xiao-Ming; Shao, Yong-Fu; Xiao, Bing-Xiu; Guo, Jun-Ming

2014-01-01

209

Gastric Electrical Stimulation for Gastroparesis  

PubMed Central

Gastric electrical stimulation (GES) for gastroparesis has been in use for more than a decade. Multiple publications, consisting almost entirely of open label single center studies, reported a beneficial effect on symptoms, quality of life and nutritional status. Some predictors of better response to GES have been lately identified, primarily diabetic etiology and nausea and vomiting as the predominant symptoms. However, individual response to GES remains difficult to predict. The mechanism of action of GES remains poorly understood. Stimulation parameters approved in clinical practice do not regulate gastric slow wave activity and have inconsistent effect on gastric emptying. Despite such limitations, gastric electrical stimulation remains a helpful intervention in some patients with severe gastroparesis who fail to respond to medical therapy.

2012-01-01

210

Capsaicin and gastric ulcers.  

PubMed

In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation. The prevalent notion among sections of population in this country and perhaps in others is that "red pepper" popularly known as "Chilli," a common spice consumed in excessive amounts leads to "gastric ulcers" in view of its irritant and likely acid secreting nature. Persons with ulcers are advised either to limit or avoid its use. However, investigations carried out in recent years have revealed that chilli or its active principle "capsaicin" is not the cause for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits acid secretion, stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury causing agents. Epidemiologic surveys in Singapore have shown that gastric ulcers are three times more common in the "Chinese" than among Malaysians and Indians who are in the habit of consuming more chillis. Ulcers are common among people who are in the habit of taking NSAIDS and are infected with the organism "Helicobacter Pylori," responsible for excessive acid secretion and erosion of the mucosal layer. Eradication of the bacteria by antibiotic treatment and avoiding the NSAIDS eliminates ulcers and restores normal acid secretion. PMID:16621751

Satyanarayana, M N

2006-01-01

211

Detection of ouabain-insensitive H(+)-transporting, K(+)-stimulated p-nitrophenylphosphatase activity in rat gastric glands by cerium-based cytochemistry.  

PubMed

We employed a modification of our previously reported cerium-based cytochemical method for ouabain-sensitive, K-dependent p-nitrophenylphosphatase (Na-K ATPase) activity to detect ouabain-insensitive, K-stimulated p-nitrophenylphosphatase (K-pNPPase) activity in rat gastric glands. Biochemically, the enzyme activity of gastric glands incubated in a medium containing 50 mM Tricine buffer (pH 7.5), 50 mM KCl, 10 mM MgCl2, 2 mM CeCl3, 2 mM p-nitrophenylphosphate (pNPP), 2.5 mM levamisole, 10 mM ouabain, and 0.00015% Triton X-100, was optimal at pH 7.5-8.0 and decreased above pH 8.5. The amount of p-nitrophenol after incubation increased linearly in proportion to the amount of tissue in the medium. The enzyme activity was inhibited by omeprazole, sodium flouride (NaF), N-ethylmaleimide (NEM), and dicyclohexylcarbodiimide (DCCD). Heat-treated specimens had no enzyme activity. The enzyme activity increased with addition of K ions up to the concentration of 50 mM, and became constant above 50 mM. Cytochemically, the parietal cells of the gastric glands reacted positively for ouabain-insensitive K-pNPPase activity. Intense reaction was observed at the microvilli of the luminal surface and the intracellular canaliculi. The tubulovesicular system showed weak enzyme activity. The reaction products were found as fine, granular, electron-dense deposits in the cytoplasm just beneath the plasma membrane. The ouabain-insensitive K-pNPPase activity detected in this study appears, therefore, to be associated with that of H-transporting, K-stimulated adenosine triphosphatase (H-K ATPase). PMID:2174937

Kobayashi, T; Seguchi, H

1990-12-01

212

Type II cGMP?dependent protein kinase inhibits RhoA activation in gastric cancer cells.  

PubMed

Small GTPase RhoA is a key signaling component regulating cell migration and stress fiber formation. Previous studies have shown that RhoA activity is regulated by protein kinases, such as cAMP?dependent protein kinase (PKA) and type I cGMP?dependent protein kinase (PKGI), which phosphorylate the protein. This study was designed to investigate the effect of type II cGMP?dependent protein kinase (PKGII) on RhoA activity. Cells of the human gastric cancer line AGS were infected with adenoviral constructs bearing the PKGII cDNA in order to increase its endogenous expression, and were treated with 8?pCPT?cGMP to activate the PKGII enzyme. A transwell assay was performed to measure the migratory activity of the treated cells, and immunofluorescent microscopy was used to observe the formation of stress fibers. The phosphorylation of RhoA was detected by western blotting, and the activity of RhoA was measured by a pull?down assay. Co?immunoprecipitation (co?IP) was performed to detect binding of PKGII to RhoA. Glutathione S?transferase (GST)?fused fragments of RhoA and PKGII were expressed in Escherichia coli and used to investigate the domains required for the binding. The results showed that lysophosphatidic acid (LPA) treatment increased the migration and the formation of stress fibers in AGS cells and that this effect was RhoA?dependent. An increase in PKGII activity, not only inhibited LPA?induced migration and stress fiber formation, but also suppressed LPA?induced activation of RhoA. PKGII caused serine 188 (Ser188) phosphorylation of RhoA, but not the phosphorylation of the mutant RhoA Ser188A, and therefore had no inhibitory effect on the activity of the mutant protein. Co?IP results showed that there is direct binding of PKGII to RhoA. The GST pull?down assay showed that the fragment containing RhoA amino acid residues 1?44 and the N?terminal fragment of PKGII containing amino acid residues 1?176 are required for the binding between the two proteins. These results suggested that PKGII inhibits RhoA activity by binding to this small GTPase and causing phosphorylation at its Ser188 site. PMID:24549567

Wang, Ying; Chen, Yongchang; Li, Yueying; Lan, Ting; Qian, Hai

2014-04-01

213

Suppression of CD74 expression and Helicobacter pylori adhesion by auraptene targeting serum starvation-activated ERK1/2 in NCI-N87 gastric carcinoma cells.  

PubMed

Helicobacter pylori (H. pylori) is a major human pathogen and plays a central role in chronic gastritis and gastric cancer. Since the adhesion of H. pylori to the human gastric epithelium is the initial and critical step of its infection, anti-H. pylori adhesion agents may be effective for the prevention and therapy of H. pylori-associated diseases. CD74 has recently been identified as a new receptor for H. pylori urease, and we have previously reported that several citrus components strongly suppressed CD74 expression in NCI-N87 gastric carcinoma cells. We found in this present study that auraptene (citrus coumarin) disrupted serum starvation-induced extracellular signaling-regulated kinase (ERK) 1/2 activation and attenuated H. pylori adhesion and IL-8 production in a co-culture system. In addition, the knockdown of CD74 expression led to a significant decrease of H. pylori adhesion, but unexpectedly increased IL-8 production. However, PD98059 (a MEK1/2 inhibitor) dramatically down-regulated this cytokine, suggesting MEK/ERK-dependent IL-8 production. Our results suggest that auraptene suppressed H. pylori adhesion and resulting chemokine production by disrupting ERK1/2 activation. PMID:20460732

Sekiguchi, Hirotaka; Irie, Kazuhiro; Murakami, Akira

2010-01-01

214

Transcriptional activation of the human claudin-18 gene promoter through two AP-1 motifs in PMA-stimulated MKN45 gastric cancer cells.  

PubMed

Claudin-18 (CLDN18), a member of the claudin family of proteins that are structural components of tight junctions, has two alternatively spliced variants, claudin-18a1 and claudin-18a2, which are highly expressed in lung and stomach, respectively. Downregulation of claudin-18a2 is associated with gastric cancers of an intestinal phenotype; however, the mechanisms regulating its expression have not been defined. Here, we found that phorbol 12-myristate 13-acetate (PMA) treatment of MKN45 human gastric cancer cell line increased claudin-18a2 expression. In addition, this study aimed to characterize the human CLDN18a2 promoter. Using reporter gene assays and deletion analysis, we mapped the critical promoter region of the PMA-stimulated claudin-18a2 expression to the -923/-286 region. Electrophoretic mobility shift assays and mutational analyses revealed that two activator protein (AP)-1 binding sites played an important role in the expression of claudin-18a2 in PMA-stimulated MKN45 cells. Protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors suppressed the upregulation of claudin-18a2. These results indicate that the PKC/MAPK/AP-1 dependent pathway regulates claudin-18a2 expression in gastric cells. PMID:18032479

Yano, Koichi; Imaeda, Takashi; Niimi, Tomoaki

2008-01-01

215

Dihydropyrimidine dehydrogenase (DPD) activity in gastric cancer tissue and effect of DPD inhibitory fluoropyrimidines  

Microsoft Academic Search

Background. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur uracil [UFT], tegafur gimeracil osteracil [S-1 (TS-1®)]) relative to DPD activity, with other fluoropyrimidines as controls. Methods. The efficacy of DIF relative to DPD activity was evaluated in 58

Hisashi Usuki; Ken Ishimura; Shinichi Yachida; Masanobu Hagiike; Keiichi Okano; Kunihiko Izuishi; Yukihiko Karasawa; Fuminori Goda; Hajime Maeta

2003-01-01

216

Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man  

Microsoft Academic Search

BACKGROUNDIn animals, activation of 5-HT1 like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones.AIMSTo investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT1receptors, on fasting fundus tone and sensitivity to gastric distension in man.METHODSA gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal

J Tack; B Coulie; A Wilmer; A Andrioli; J Janssens

2000-01-01

217

The effect of ethanol and pH on the adsorption of drugs from simulated gastric fluid onto activated charcoal.  

PubMed

The effect of ethanol and pH on the adsorption of acetaminophen (ACET), phenobarbital (PHB), phenytoin (PHY), salicylic acid (SA), and theophylline (THEO) from simulated gastric fluid onto activated charcoal was studied. For the ethanol study, each drug was prepared at a concentration of 10 g/L in ethanol; in hydrochloric acid (HCl), 1.2 mol/L; and in HCl, 1.2 mol/L, containing 75% ethanol, 50% ethanol, and 25% ethanol (v/v), respectively. For the pH study, each drug was prepared at a concentration of 10 g/L in HCl, 1.2 mol/L, pH 1.0, and in buffers of pH 1.7, 3.0, 4.0, 4.8, 5.8, 6.5, 7.4, and 9.4. After the addition of 1 g of activated charcoal to 10 mL of each solution, it was incubated for one hour at 37 degrees C. For comparison, in each experiment a blank consisting of the solution without charcoal was also incubated. With increasing concentrations of ethanol, there were substantial decreases in the adsorption of ACET, PHB, and PHY to charcoal. Ethanol-induced decreases in the adsorption of SA and THEO were less pronounced. Changes in pH did not affect the adsorption of ACET, PHB, PHY, or THEO. However, the adsorption of SA was decreased slightly at pH 1.0 and 3.0. PMID:12766559

Bailey, David N; Briggs, John R

2003-06-01

218

Calpain 8/nCL-2 and Calpain 9/nCL-4 Constitute an Active Protease Complex, G-Calpain, Involved in Gastric Mucosal Defense  

PubMed Central

Calpains constitute a superfamily of Ca2+-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus (pit) cells in the stomach. Possible functions reported for calpain 8 are in vesicle trafficking between ER and Golgi, and calpain 9 are implicated in suppressing tumorigenesis. These highlight that calpains 8 and 9 are regulated differently from each other and from conventional calpains and, thus, have potentially important, specific functions in the gastrointestinal tract. However, there is no direct evidence implicating calpain 8 or 9 in human disease, and their properties and physiological functions are currently unknown. To address their physiological roles, we analyzed mice with mutations in the genes for these calpains, Capn8 and Capn9. Capn8?/? and Capn9?/? mice were fertile, and their gastric mucosae appeared normal. However, both mice were susceptible to gastric mucosal injury induced by ethanol administration. Moreover, the Capn8?/? stomach showed significant decreases in both calpains 9 and 8, and the same was true for Capn9?/?. Consistent with this finding, in the wild-type stomach, calpains 8 and 9 formed a complex we termed “G-calpain,” in which both were essential for activity. This is the first example of a “hybrid” calpain complex. To address the physiological relevance of the calpain 8 proteolytic activity, we generated calpain 8:C105S “knock-in” (Capn8CS/CS) mice, which expressed a proteolytically inactive, but structurally intact, calpain 8. Although, unlike the Capn8?/? stomach, that of the Capn8CS/CS mice expressed a stable and active calpain 9, the mice were susceptible to ethanol-induced gastric injury. These results provide the first evidence that both of the gastrointestinal-tract-specific calpains are essential for gastric mucosal defense, and they point to G-calpain as a potential target for gastropathies caused by external stresses.

Hata, Shoji; Abe, Manabu; Suzuki, Hidenori; Kitamura, Fujiko; Toyama-Sorimachi, Noriko; Abe, Keiko; Sakimura, Kenji; Sorimachi, Hiroyuki

2010-01-01

219

Ultrafine particles of Ulmus davidiana var. japonica induce apoptosis of gastric cancer cells via activation of caspase and endoplasmic reticulum stress.  

PubMed

Small-sized particles are more suitable for targeted delivery and are therapeutically more effective than large-sized particles. In this study, we investigated the anticancer effects of ultrafine particles of Ulmus davidiana var. japonica (ufUJ) on human gastric cancer cell lines SNU-1, SNU-216, and SNU-484. ufUJ induced apoptosis by the proteolytic activation of caspase-9, caspase-6, and caspase-3 and cleavage of poly (ADP-ribose) polymerase. The expression levels of the endoplasmic reticulum stress-related protein BiP markedly increased after ufUJ treatment. BiP knockdown decreased ufUJ-induced cell death. ufUJ-induced apoptosis was inhibited by the caspase-3 inhibitor z-DEVD-fmk, caspase-6 inhibitor z-VEID-fmk, and caspase-9 inhibitor z-LEHD-fmk, and by siRNAs against caspases 3, 6, and 9. Gastric cancer cells did not show anchorage-independent growth in the presence of ufUJ. However, cells treated with caspase inhibitors showed an enhanced colony-forming ability. These findings may be helpful in the prevention of gastric cancer and in the development of functional foods. PMID:24395528

Ahn, Joungjwa; Lee, Jong Suk; Yang, Kyung Mi

2014-06-01

220

Component analysis and structure identification of active substances for anti-gastric ulcer effects in Radix Astragali by liquid chromatography and tandem mass spectrometry.  

PubMed

This study provided a comprehensive component analysis and structure identification of active substances for the anti-gastric ulcer effects of Radix Astragali. The data were generated by organically combining the results from in vivo pharmacodynamic experiments, a cell growth-promoting assay, structure identification, content determination, fingerprinting, and correlation analyses. The fingerprints from high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) and from HPLC coupled with evaporative light scattering detectors (ELSD) from 95% ethanol extracts of Radix Astragali (ERA) were determined using HPLC-DAD-ELSD. The structures of 16 compounds were identified using ultra-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS). The contents of these 16 compounds were simultaneously determined in a single run using HPLC-DAD-ELSD. The strength of the anti-ulceration effect of each of the 16 compounds was correlated to its content in the HPLC spectrum using gray relation statistics. The sequence of the contribution from each of the 16 compounds to the anti-gastric ulcer effect was determined. The results showed that ononin, astragalosideIII, and astragalosideIV contributed most to the observed anti-gastric ulcer effects and that these three compounds also exhibited strong growth-promoting effects in cultured GES-1 cells. The results of this study can be used to evaluate the quality of Radix Astragali and to provide a theoretical foundation for its further study. PMID:24780704

Liu, Xiao-Hua; Zhao, Liang-Gong; Liang, Jing; Guo, Long; Yang, Ying-Lai; Hu, Fang; Zhu, Rui-Juan; Feng, Shi-Lan

2014-06-01

221

Metallothionein 2A inhibits NF-?B pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection  

PubMed Central

Background Metallothionein 2A (MT2A) as a stress protein, plays a protective role in gastric mucosal barrier. Its role in the development of gastric cancer (GC) is unclear. The mechanism of MT2A will be investigated in gastric tumorigenesis. Methods MT2A expression was detected in 973 gastric specimens. The biological function was determined through ectopic expressing MT2A in vitro and in vivo. The possible downstream effectors of MT2A were investigated in NF-?B signaling. The protein levels of MT2A, I?B-? and p-I?B-? (ser32/36) expression were analyzed in a subset of 258 patients by IHC staining. The prognostic effects of MT2A, status of I?B-? and TNM stage were evaluated using the Kaplan-Meier method and compared using the log-rank test. Results Decreased MT2A expression was detected in cell lines and primary tumors of GC. In clinical data, loss of MT2A (MT2A?+?in Normal (n =171, 76.0%); Intestinal metaplasia (n?=?118, 50.8%); GC (n?=?684. 22.4%, P?activity through inhibiting NF-?B signaling and may be a prognostic biomarker and potential target for individual therapy of GC patients.

2013-01-01

222

Diffuse gastric cancer.  

PubMed

Gastric cancer is one of the leading causes of cancer deaths around the world. This article provides an overview of gastric cancer using a unique case study involving a New Zealand Maori family genetically predisposed to diffuse gastric cancer. The pathophysiology of diffuse gastric cancer, including prognosis, diagnosis, and treatment, along with important patient considerations is highlighted. PMID:16770139

Framp, Ann

2006-01-01

223

In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats  

PubMed Central

Background The current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats. Methodology/Principal Findings Sprague Dawley rats were separated into 7 groups. Groups 1–2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4–7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2–7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4–7. Groups 3–7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests. Conclusion Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2).

Al Batran, Rami; Al-Bayaty, Fouad; Jamil Al-Obaidi, Mazen M.; Abdualkader, Abdualrahman Mohammed; Hadi, Hamid A.; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

2013-01-01

224

IL-26 Promotes the Proliferation and Survival of Human Gastric Cancer Cells by Regulating the Balance of STAT1 and STAT3 Activation  

PubMed Central

Interleukin-26 (IL-26) is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC). The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling.

Zhang, Chuanyong; Wu, Jindao; Gu, Chunrong; Wu, Zhengshan; Li, Xiangcheng

2013-01-01

225

Metformin directly inhibits ghrelin secretion through AMP-activated protein kinase in rat primary gastric cells.  

PubMed

The antidiabetic drug Metformin causes weight loss in both diabetic and non-diabetic individuals. Metformin treatment is also associated with lower circulating levels of the orexigenic hormone ghrelin. To test whether Metformin directly affects ghrelin cells, rat primary stomach cells were treated with Metformin and the levels of ghrelin secretion, proghrelin gene expression and activation of adenosine monophosphate-activated protein kinase (AMPK) were examined. Metformin significantly reduced ghrelin secretion and proghrelin mRNA production and both these effects were blocked by co-incubation with the AMPK inhibitor compound C. Furthermore, the AMPK activator 5-amino-1-?-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) significantly inhibited ghrelin secretion. Additionally, ghrelin cells were shown to express AMPK. Finally, Metformin treatment caused a significant increase in the level of phosphorylated (active) AMPK. Our results show that Metformin directly inhibits stomach ghrelin production and secretion through AMPK. This reduction in ghrelin secretion may be one of the key components in Metformin's mechanism of weight loss. PMID:23066988

Gagnon, J; Sheppard, E; Anini, Y

2013-03-01

226

Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: Analysis of underlying mechanisms  

Microsoft Academic Search

Ethnopharmacological relevanceBaccharis trimera (Less.) DC. (Asteraceae) is a species native to South America used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. Previous studies from this laboratory confirmed the antacid and antiulcer activities of the plant aqueous extract (AE) in rat and mouse models.

Thais Maíra A. Biondo; Mirtes M. Tanae; Eliana Della Coletta; Maria Teresa R. Lima-Landman; Antonio J. Lapa; Caden Souccar

2011-01-01

227

Acidic digestion in a teleost: postprandial and circadian pattern of gastric pH, pepsin activity, and pepsinogen and proton pump mRNAs expression.  

PubMed

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices. PMID:22448266

Yúfera, Manuel; Moyano, Francisco J; Astola, Antonio; Pousão-Ferreira, Pedro; Martínez-Rodríguez, Gonzalo

2012-01-01

228

Nonsteroidal anti-inflammatory drug-activated gene-1 plays a role in the impairing effects of cyclooxygenase inhibitors on gastric ulcer healing.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) can impair gastric ulcer healing. This study investigates the involvement of NSAID-activated gene-1 (NAG-1) in ulcer repair impairment by cyclooxygenase (COX) inhibitors. Gastric ulcers were induced in rats by acetic acid. Four days later, animals received daily intragastric indomethacin (nonselective COX-1/COX-2 inhibitor; 1 mg/kg), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) (selective COX-1 inhibitor; 2.5 mg/kg), (5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) (selective COX-2 inhibitor; 5 mg/kg), celecoxib (selective COX-2 inhibitor; 1 mg/kg), and valdecoxib (selective COX-2 inhibitor; 1 mg/kg), for 1, 3, or 7 days. Ulcerated tissues were processed to assess: 1) COX-1, COX-2, NAG-1, proliferating cell nuclear antigen (PCNA), and activated caspase-3 expression; 2) ulcer area; and 3) prostaglandin E(2) (PGE(2)) levels. COX-1 expression in ulcerated tissues was decreased, whereas COX-2 expression was enhanced. Ulcer healing was delayed by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. Ulcer PGE(2) levels were decreased by SC-560, DFU, celecoxib, valdecoxib, and indomethacin. NAG-1 was overexpressed in ulcerated tissues and further enhanced by indomethacin, DFU, and SC-560, but not by celecoxib or valdecoxib. PCNA expression in ulcerated areas was reduced by indomethacin, but not by the other test drugs. The expression of activated caspase-3 in ulcers was increased and enhanced further by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. These findings indicate that: 1) COX inhibitors exert differential impairing effects on gastric ulcer healing, through mechanisms unrelated to the inhibition of COX isoforms and prostaglandin production; and 2) NAG-1 induction, followed by activation of proapoptotic pathways, can contribute to the impairing effects of COX inhibitors on ulcer healing. PMID:22495067

Colucci, Rocchina; Antonioli, Luca; Bernardini, Nunzia; Ippolito, Chiara; Segnani, Cristina; Awwad, Oriana; Tuccori, Marco; Blandizzi, Corrado; Scarpignato, Carmelo; Fornai, Matteo

2012-07-01

229

Acidic Digestion in a Teleost: Postprandial and Circadian Pattern of Gastric pH, Pepsin Activity, and Pepsinogen and Proton Pump mRNAs Expression  

PubMed Central

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices.

Yufera, Manuel; Moyano, Francisco J.; Astola, Antonio; Pousao-Ferreira, Pedro; Martinez-Rodriguez, Gonzalo

2012-01-01

230

Orally Active Fumagillin Analogues: Transformations of a Reactive Warhead in the Gastric Environment  

PubMed Central

Semisynthetic analogues of fumagillin, 1, inhibit methionine aminopeptidase-2 (MetAP2) and have entered the clinic for the treatment of cancer. An optimized fumagillin analogue, 3 (PPI-2458), was found to be orally active, despite containing a spiroepoxide function that formed a covalent linkage to the target protein. In aqueous acid, 3 underwent ring-opening addition of water and HCl, leading to four products, 4–7, which were characterized in detail. The chlorohydrin, but not the diol, products inhibited MetAP2 under weakly basic conditions, suggesting reversion to epoxide as a step in the mechanism. In agreement, chlorohydrin 6 was shown to revert rapidly to 3 in rat plasma. In an ex vivo assay, rats treated with purified acid degradants demonstrated inhibition of MetAP2 that correlated with the biochemical activity of the compounds. Taken together, the results indicate that degradation of the parent compound was compensated by the formation of active equivalents leading to a pharmacologically useful level of MetAP2 inhibition.

2013-01-01

231

The negative charge of glutamic acid-820 in the gastric H+,K+-ATPase alpha-subunit is essential for K+ activation of the enzyme activity.  

PubMed Central

To investigate the role of Glu820, located in transmembrane domain M6 of the alpha-subunit of gastric H+,K+-ATPase, a number of mutants was prepared and expressed in Sf9 cells using a baculovirus encoding for both H+,K+-ATPase subunits. The wild-type enzyme and the E820D (Glu820-->Asp) mutant showed a similar biphasic activation by K+ on the ATPase activity (maximum at 1 mM). The mutant E820A had a markedly decreased K+ affinity (maximum at 40-100 mM). The other mutants, E820Q, E820N, E820L and E820K, showed no K+-activated ATPase activity at all, whereas all mutants formed a phosphorylated intermediate. After preincubation with K+ before phosphorylation mutant E820D showed a similar K+-sensitivity as the wild-type enzyme. The mutants E820N and E820Q had a 10-20 times lower sensitivity, whereas the other three mutants were hardly sensitive towards K+. Upon preincubation with 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy) imidazo [1,2a]-pyridine (SCH28080), all mutants showed similar sensitivity for this drug as the wild-type enzyme, except mutant E820Q, which could only partly be inhibited, and mutant E820K, which was completely insensitive towards SCH28080. These experiments suggest that, with a relatively large residue at position 820, the binding of SCH28080 is obstructed. The various mutants showed a behaviour in K+-stimulated-dephosphorylation experiments similar to that for K+-activated-ATPase-activity measurements. These results indicate that K+ binding, and indirectly the transition to the E2 form, is only fully possible when a negatively charged residue is present at position 820 in the alpha-subunit.

Hermsen, H P; Swarts, H G; Koenderink, J B; De Pont, J J

1998-01-01

232

The negative charge of glutamic acid-820 in the gastric H+,K+-ATPase alpha-subunit is essential for K+ activation of the enzyme activity.  

PubMed

To investigate the role of Glu820, located in transmembrane domain M6 of the alpha-subunit of gastric H+,K+-ATPase, a number of mutants was prepared and expressed in Sf9 cells using a baculovirus encoding for both H+,K+-ATPase subunits. The wild-type enzyme and the E820D (Glu820-->Asp) mutant showed a similar biphasic activation by K+ on the ATPase activity (maximum at 1 mM). The mutant E820A had a markedly decreased K+ affinity (maximum at 40-100 mM). The other mutants, E820Q, E820N, E820L and E820K, showed no K+-activated ATPase activity at all, whereas all mutants formed a phosphorylated intermediate. After preincubation with K+ before phosphorylation mutant E820D showed a similar K+-sensitivity as the wild-type enzyme. The mutants E820N and E820Q had a 10-20 times lower sensitivity, whereas the other three mutants were hardly sensitive towards K+. Upon preincubation with 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy) imidazo [1,2a]-pyridine (SCH28080), all mutants showed similar sensitivity for this drug as the wild-type enzyme, except mutant E820Q, which could only partly be inhibited, and mutant E820K, which was completely insensitive towards SCH28080. These experiments suggest that, with a relatively large residue at position 820, the binding of SCH28080 is obstructed. The various mutants showed a behaviour in K+-stimulated-dephosphorylation experiments similar to that for K+-activated-ATPase-activity measurements. These results indicate that K+ binding, and indirectly the transition to the E2 form, is only fully possible when a negatively charged residue is present at position 820 in the alpha-subunit. PMID:9531486

Hermsen, H P; Swarts, H G; Koenderink, J B; De Pont, J J

1998-04-15

233

Chemotherapy for gastric cancer  

PubMed Central

Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase II and III studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed. Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase III trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116 study, postoperative chemoradiation has been accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase II studies are showing promising results. Phase III trials are needed.

Sastre, Javier; Garcia-Saenz, Jose Angel; Diaz-Rubio, Eduardo

2006-01-01

234

Role of NK1 and NK2 receptors in mouse gastric mechanical activity  

PubMed Central

The aim of the present study was to examine the role of NK1 and NK2 receptors in the control of mechanical activity of mouse stomach. In this view, the motor effects induced by NK1 and NK2 receptor agonists and antagonists were analyzed, measuring motility as intraluminal pressure changes in mouse-isolated stomach preparations. In parallel, immunohistochemical studies were performed to identify the location of NK1 and NK2 receptors on myenteric neurons and smooth muscle cells.Substance P (SP) induced biphasic effects: a contraction followed by relaxation; neurokinin A (NKA) and [?-Ala8]-NKA(4?10), selective agonist of NK2 receptors, evoked concentration-dependent contractions, whereas [Sar9, Met(O2)11]-SP, selective agonist of NK1 receptors, induced concentration-dependent relaxation.SR48968, NK2 receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation. SR140333, NK1 receptor antagonist, did not modify the spontaneous activity and antagonized the relaxant response to tachykinins, failing to affect the contractile effects.The relaxation to SP or to [Sar9, Met(O2)11]-SP was abolished by tetrodotoxin (TTX) and significantly reduced by N?-nitro-L-arginine methyl ester (L-NAME).NK2-immunoreactivity (NK2-IR) was seen at the level of the smooth muscle cells of both circular and longitudinal muscle layers. NK1-immunoreactive (NK1-IR) neurons were seen in the myenteric ganglia and NK1/nNOS double labeling revealed that some neurons were both NK1-IR and nNOS-IR.These results suggest that, in mouse stomach, NK1 receptors, causing relaxant responses, are present on nitrergic inhibitory myenteric neurons, whereas NK2 receptors, mediating contractile responses, are present at muscular level.

Mule, Flavia; Amato, Antonella; Vannucchi, Maria Giuliana; Faussone-Pellegrini, Maria Simonetta; Serio, Rosa

2006-01-01

235

FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic significance and assessment of downstream pathway activation.  

PubMed

Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P?=?0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P?=?0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P?gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials. PMID:24306956

Betts, Guy; Valentine, Helen; Pritchard, Sue; Swindell, Richard; Williams, Victoria; Morgan, Shethah; Griffiths, Ewen A; Welch, Ian; West, Catharine; Womack, Christopher

2014-02-01

236

Isorhamnetin Inhibits Proliferation and Invasion and Induces Apoptosis through the Modulation of Peroxisome Proliferator-activated Receptor ? Activation Pathway in Gastric Cancer*  

PubMed Central

Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3?-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor ? (PPAR-?) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-? inhibitor. We found that IH increased PPAR-? activity and modulated the expression of PPAR-? regulated genes in GC cells. Also, the increase in PPAR-? activity was reversed in the presence of PPAR-?-specific inhibitor and a mutated PPAR-? dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-?. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-? that are reported to be critical for its activity and could competitively bind to PPAR-?. IH significantly increased the expression of PPAR-? in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-? activation pathway in GC.

Ramachandran, Lalitha; Manu, Kanjoormana Aryan; Shanmugam, Muthu K.; Li, Feng; Siveen, Kodappully Sivaraman; Vali, Shireen; Kapoor, Shweta; Abbasi, Taher; Surana, Rohit; Smoot, Duane T.; Ashktorab, Hassan; Tan, Patrick; Ahn, Kwang Seok; Yap, Chun Wei; Kumar, Alan Prem; Sethi, Gautam

2012-01-01

237

Effects of Anethum graveolens L. seed extracts on experimental gastric irritation models in mice  

PubMed Central

Background As a folk remedy, Anethum graveolens seed (dill) is used for some gastrointestinal ailments. We aimed to evaluate aqueous and ethanolic extracts of anti-ulcer and acute toxicity effects of the Anethum graveolens in mice. Results Gastric mucosal lesions were induced by oral administration of HCl (1 N) and absolute ethanol in mice. The acidity and total acid content of gastric juice were measured in pylorus-ligated mice. LD50 values of the aqueous and ethanolic extracts were 3.04 g/kg, i.p., (1.5, 6.16) and 6.98 g/kg, i.p., (5.69, 8.56), respectively. The efficacy of high dose of extracts (p.o.) was similar to sucralfate. The acidity and total acid content were reduced by the orally or intraperitoneally administration of the extracts. Conclusions The results suggest that A. graveolens seed extracts have significant mucosal protective and antisecretory effects of the gastric mucosa in mice.

Hosseinzadeh, Hossein; Karimi, Gholam_Reza; Ameri, Maryam

2002-01-01

238

Two-channel gastric pacing in patients with diabetic gastroparesis  

PubMed Central

Background Our primary goals were to investigate the effects of two-channel gastric pacing on gastric myoelectrical activity, and energy consumption with the secondary intent to monitor gastric emptying and symptoms in patients with severe diabetic gastroparesis. Methods Four pairs of temporary pacing wires were inserted on the serosa of the stomach at the time of laparotomy to place the Enterra™ System in 19 patients with severe gastroparesis not responding to standard medical therapies. Two of the pairs were for electrical stimulation and the other two for recording. Five days after surgery the optimal pacing parameters for the entrainment of gastric slow waves in each patient were identified by serosal recordings. Two-channel gastric pacing was then initiated for 6 weeks using a newly developed external multi-channel pulse generator. Electrogastrogram (EGG), total symptom score (TSS), and a 4-hour gastric emptying test were assessed at baseline and after 6 weeks of active gastric pacing. Enterra™ device was turned OFF during the duration of this study. Key Results Two-channel gastric pacing at 1.1 times the intrinsic frequency entrained gastric slow waves and normalized gastric dysrhythmia. After 6 weeks of gastric pacing, tachygastria was decreased from 15±3 to 5±1% in the fasting state and from 10±2 to 5±1% postprandially (P<0.05), mean TSS was reduced from 21.3±1.1 to 7.0±1.5 (P<0.05) and mean 4-hour gastric retention improved from 42% to 28% (P=0.05). Conclusions& Inferences Two-channel gastric pacing is a novel treatment approach which is able to normalize and enhance gastric slow wave activity as well as accelerate gastric emptying in patients with diabetic gastroparesis with a good safety profile.

Lin, Zhiyue; Sarosiek, Irene; Forster, Jameson; Ross, Robert A.; Chen, Jiande D.Z.; McCallum, Richard W.

2011-01-01

239

A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model  

PubMed Central

Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual plant extracts and the mixed extracts of 5 plants exhibited weak to moderate antibacterial activity against four G-ve bacteria. Despite Ozoroa insignis being toxic to mice at doses above 1000 mg/kg body wt, the other plant extracts and the combined extract of the 5 plants were tolerated by mice up to 5000 mg/kg body wt. The brine shrimp test results showed the same pattern of toxicity with Ozoroa insignis being the most toxic (LC50?=?10.63 ?g/ml). Phytochemical tests showed that the combined extract of the five plants contained tannins, saponins, steroids, cardiac glycosides, flavonoids and terpenoids. Flavonoids, tannins and terpenoids are known to have antioxidant activity. Conclusion The combined extract of the five plants exhibited a dose-dependent protective activity in the rat ethanol-HCl gastric ulcer model. The extracts also exhibited weak antibacterial activity against four Gram negative bacteria and low acute toxicity in mice and brine shrimps. Although the results support claims by traditional healers who use a decoction of the five plants for treatment of peptic ulcers, more models of gastric ulceration and proper animal toxicity studies are needed to validate possible clinical use of the polyherbal extract. It is also evident that the doses of the crude extracts showing protection of the gastric mucosa are too large for realistic translation to direct clinical application, but further studies using bioassay guided fractionation are important to either identify more practical fractions or active compound/s.

2012-01-01

240

The relationship between gastric motility and nausea: gastric prokinetic agents as treatments.  

PubMed

Nausea is one of a cluster of symptoms described subjectively by patients with delayed gastric emptying. The mechanisms and treatments are unclear (anti-emetic drugs are not fully effective against nausea). Can nausea be relieved by stimulating gastric emptying? Physostigmine (together with atropine) has been shown experimentally to stimulate gastric motility, relieve nausea and restore normal gastric motility. Is this mimicked by gastric prokinetic drugs? The answer is complicated by mixed pharmacology. Metoclopramide increases gastric motility by activating myenteric 5-HT4 receptors but also directly inhibits vomiting via D2 and 5-HT3 receptor antagonism; relationships between increased gastric motility and relief from nausea are therefore unclear. Similarly, the D2 receptor antagonist domperidone has direct anti-emetic activity. Nevertheless, more selective 5-HT4 and motilin receptor agonists (erythromycin, directly stimulating gastric motility) inhibit vomiting in animals; low doses of erythromycin can also relieve symptoms in patients with gastroparesis. Ghrelin stimulates gastric motility and appetite mostly via vagus-dependent pathways, and inhibits vomiting in animals. To date, ghrelin receptor activation has failed to consistently improve gastric emptying or symptoms in patients with gastroparesis. We conclude that nausea can be relieved by gastric prokinetic drugs, but more clinical studies are needed using drugs with selective activity. Other mechanisms (e.g. ghrelin, vagal and central pathways, influencing a mechanistic continuum between appetite and nausea) also require exploration. These and other issues will be further explored in a forthcoming special issue of the European Journal of Pharmacology, which focusses on mechanisms of nausea and vomiting. PMID:23831391

Sanger, Gareth J; Broad, John; Andrews, Paul L R

2013-09-01

241

Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients: A prospective study.  

PubMed

The identification of circulating tumor cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression and measure treatment effects in several types of malignancies. We have previously used OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. GFP-positive cells (GFP+ cells) were counted under a fluorescence microscope. Our results showed that the number of at least 7.735 µm in diameter GFP+ cells (L-GFP+ cells) in the peripheral blood was a significant marker of prognosis in gastric cancer patients. However, tumor cells undergoing epithelial-mesenchymal transition (EMT) have been reported to be smaller in size than cells without EMT features; thus, CTCs undergoing EMT may escape detection with this technique. Therefore, in this study, we analyzed the relationship between patient outcome and the number of GFP+ cells of any size. We obtained peripheral blood samples from 65 patients with gastric cancer. After infection of OBP-401, GFP+ cells were counted and measured. The relationship between the number of GFP+ cells and surgical outcome was analyzed. The median follow-up period of the surviving patients was 36 months. A significant difference in overall survival was found between patients with 0-5 and patients with ?6 L-GFP+ cells. No clear relationship was established between the number of small-sized GFP+ cells and patient prognosis. The number of L-GFP+ cells was significantly related to overall survival in patients with gastric cancer. The detection of L-GFP+ cells using OBP-401 may be a useful prognostic marker in gastric cancer. PMID:24788213

Ito, Hiroaki; Inoue, Haruhiro; Kimura, Satoshi; Ohmori, Tohru; Ishikawa, Fumihiro; Gohda, Keigo; Sato, Jun

2014-07-01

242

Activation of Ca(2+)-dependent K+ current by acetylcholine and histamine in a human gastric epithelial cell line  

Microsoft Academic Search

The effects of acetylcholine (ACh) and histamine (His) on the mem- brane potential and current were examined in JR-1 cells, a mucin-producing epithelial cell line derived from human gastric signet ring cell carcinoma. The tight-seal, whole cell clamp technique was used. The resting membrane potential, the input resistance, and the capacitance of the cells were approximately - 12 mV, 1.4

EIJI HAMADA; TOSHIAKI NAKAJIMA; SHIN-ICHI OTA; AKIRA TERANO; MASAO OMATA; SHINJI NAKADE; KATSUHIKO MIKOSHIBA; YOSHIHISA KURACHI

1993-01-01

243

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NF?B signaling pathway  

PubMed Central

Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NF?B signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NF?B signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NF?B signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.

Wang, Jin; Kang, Wei-Ming; Yu, Jian-Chun; Liu, Yu-Qin; Meng, Qing-Bin; Cao, Zhan-Jiang

2013-01-01

244

The gastric precancerous cascade  

PubMed Central

Invasive gastric carcinoma is preceded by a cascade of precancerous lesions. The first recognized histologic change is active chronic inflammation, which may persist as such: non-atrophic chronic gastritis (no gland loss), or advance to multifocal atrophic gastritis (MAG), the first real step in the precancerous cascade. The following steps are: intestinal metaplasia (first “complete” and then “incomplete”); dysplasia, first low grade and then high grade (equivalent to “carcinoma in situ”). The following step is invasive carcinoma, which is thought to be associated with degradation of the intercellular matrix.

CORREA, Pelayo; PIAZUELO, M Blanca

2012-01-01

245

The gastric precancerous cascade.  

PubMed

Invasive gastric carcinoma is preceded by a cascade of precancerous lesions. The first recognized histologic change is active chronic inflammation, which may persist as such: non-atrophic chronic gastritis (no gland loss), or advance to multifocal atrophic gastritis (MAG), the first real step in the precancerous cascade. The following steps are: intestinal metaplasia (first "complete" and then "incomplete"); dysplasia, first low grade and then high grade (equivalent to "carcinoma in situ"). The following step is invasive carcinoma, which is thought to be associated with degradation of the intercellular matrix. PMID:22188910

Correa, Pelayo; Piazuelo, M Blanca

2012-01-01

246

A comparative pharmacological investigation of three samples of 'Guduchi ghrita' for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats.  

PubMed

This study was undertaken to investigate the impact of formulation factors and adjuvants on the expression of biological activity of Tinospora cordifolia (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita, prepared using plain ghee (clarified butter) obtained from three different sources was studied in albino rats and compared with expressed juice of stem of Guduchi. The test preparations were evaluated against forced-swimming induced hypothermia, gastric ulceration and changes in the hematological parameters. The test drug given in the form of 'ghrita' produced better effect in comparison to the expressed juice. Among the three 'ghrita' preparations evaluated, only the 'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of stress hypothermia and gastric ulceration. The other two preparations 'Nanded Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a marginal effect. In hematological parameters 'Guduchi' juice produced better reversal of the stress-induced changes in comparison to the test 'ghrita' preparations. The present study provides evidence highlighting the importance of formulation factors for the expression of biological activity. PMID:20814518

Savrikar, Shriram S; Dole, Vilas; Ravishankar, B; Shukla, Vinay J

2010-04-01

247

Rapid Gastric Emptying  

MedlinePLUS

... INSTITUTES OF HEALTH U.S. Department of Health and Human Services What is rapid gastric emptying? Rapid gastric ... Health of the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information ...

248

Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity  

PubMed Central

Background Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.

2013-01-01

249

Diversity of Gastric Carcinogenesis  

Microsoft Academic Search

Gastric cancer is still the second leading cause of cancer death worldwide, although the incidence of this disease has been gradually decreasing. The diversity of gastric cancer is well known. However, the mechanism underlying this diversity is still unknown. We have performed experimental and clinical studies on gastric carcinogenesis. These results suggest that the variety in the type and extent

Michio Kaminishi

2005-01-01

250

[Gastric epithelial dysplasia].  

PubMed

Gastric epithelial dysplasia represents the only true histological marker of gastric cancer. In this bringing up to date, such subject is reproposed in consideration of taking into account the most recent acquisitions, subdividing gastric dysplasia into two degrees only: moderate and severe. For the first time an immunophenotypic study is made by means of the evaluation of gastric-entero-pancreatic antigens, which better identify the evolutive potential of the two degrees of gastric dysplasia and, furthermore, the clinical development is evaluated, thus showing the necessity of a strict endoscopic surveillance of such lesion. PMID:11008411

Cornaggia, M; Testino, G

2000-01-01

251

Gastric anti-ulcer activity of leaf fractions obtained of polar extract from Wilbrandia ebracteata in mice  

Microsoft Academic Search

Leaf fractions of Wilbrandia ebracteata were investigated for anti-ulcerogenic effects in ethanol and indomethacin-induced gastric ulcer assays in mice. Protective anti-ulcer effects were detected only in the ethanol-induced ulcer assay effects after pre-treatment with MeOH extract, MeOH chlorophyll-free, chlorophyll residue, HEX, DCM, aqueous MeOH fraction, ethyl acetate (EtOAc) and aqueous fractions. A potent anti-ulcerogenic effect was determined after pre-treatment of

R. G. Coelho; F. G. Gonzalez; M. Sannomiya; L. C. Di Stasi; W. Vilegas

2009-01-01

252

?-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity  

PubMed Central

We examined the effects of altering ?-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 1–10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABAA receptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons.

Herman, Melissa A.; Alayan, Alisa; Sahibzada, Niaz; Bayer, Barbara; Verbalis, Joseph; Dretchen, Kenneth L.

2010-01-01

253

Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice.  

PubMed

Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity. PMID:1444220

Kubota, T; Kase, S; Furukawa, T; Tanino, H; Kuo, T H; Saikawa, Y; Nishibori, H; Ishibiki, K; Kitajima, M; Mabuchi, K

1992-01-01

254

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents  

NASA Technical Reports Server (NTRS)

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

255

Variations in NAG-1 expression of human gastric carcinoma and normal gastric tissues  

PubMed Central

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a member of the transforming growth factor ? (TGF-?) superfamily, has been demonstrated to possess antitumorigenic and proapoptotic activities in gastric cancer cells. In the present study, the expression of NAG-1 was assessed in human gastric carcinoma, tumor-adjacent normal tissues and normal gastric mucosa, with the aim to investigate the role of NAG-1 in the carcinogenesis and development of gastric carcinoma. NAG-1 protein expression was evaluated using immunohistochemical staining, while the expression of NAG-1 mRNA was evaluated using reverse transcription-polymerase chain reaction. It was observed that adenocarcinoma tissues had a lower expression of NAG-1 than normal gastric tissues. Furthermore, moderately and well-differentiated adenocarcinoma tissues expressed more NAG-1 protein than the poorly differentiated adenocarcinoma tissues. The expression of NAG-1 protein in adenocarcinoma tissues did not correlate with tumor-node-metastasis staging, infiltration degree or tumor size. The NAG-1 mRNA expression in adenocarcinoma tissues was also lower than that in normal gastric tissues. In conclusion, NAG-1 was poorly expressed in adenocarcinoma tissues and inversely correlated with the degree of tumor differentiation. These results indicate that NAG-1 may have an anti-oncogenic function in the carcinogenesis and development of gastric carcinoma, and that its attenuated or absent expression may lead to gastric carcinogenesis.

YANG, GONGLI; TAN, QINHUA; XIE, YONGMEI; WEI, BIN; CHEN, ZHIXIN; TANG, CHENGWEI; LI, SHENGBAO; WANG, CHUNHUI

2014-01-01

256

Human lysosomal acid lipase\\/cholesteryl ester hydrolase and human gastric lipase: site-directed mutagenesis of Cys227 and Cys236 results in substrate-dependent reduction of enzymatic activity  

Microsoft Academic Search

Chemical modification studies and site-directed mutagenesis experiments have provided evidence that human lysosomal acid lipase\\/ cholesteryl ester hydrolase (HLAL) , hu- man gastric lipase (HGL), and rat lingual lipase (RLL) are serine esterases. Loss of HLAL and HGL activity was also oh served in the presence of sulfhydryl-reactive substances, sug- gesting that cysteines are likewise essential for substrate hydrc- lysis.

Peter Lohse; Pia Lohse; Soheyla Chahrokh-Zadeh; Dietrich Seidel

257

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes  

PubMed Central

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50?50, by ?100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P?E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ?90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P?E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P?E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ?0.5 and ?0.2, respectively.

Durr, Katharina L.; Tavraz, Neslihan N.; Friedrich, Thomas

2012-01-01

258

Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats  

SciTech Connect

Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.

Poulsen, S.S.; Raaberg, L.; Therkelsen, K.; Skov Olsen, P.; Kirkegaard, P.

1986-07-01

259

Structure-activity relationships of ?-, ?(1)-, ?-, and ?-tomatine and tomatidine against human breast (MDA-MB-231), gastric (KATO-III), and prostate (PC3) cancer cells.  

PubMed

Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid ?-tomatine resulted in the formation of four products with three, two, one, and zero carbohydrate side chains, which were separated by high-performance liquid chromatography (HPLC) and identified by thin-layer chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC(50) values (concentration that inhibits 50% of the cells under the test conditions) of the parent compound and the hydrolysates, isolated by preparative HPLC, against normal human liver and lung cells and human breast, gastric, and prostate cancer cells indicate that (a) the removal of sugars significantly reduced the concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3 prostate cancer cells were about 10 times more susceptible to inhibition by ?-tomatine than the breast and gastric cancer cells or the normal cells, (c) the activity of ?-tomatine against the prostate cancer cells was 200 times greater than that of the aglycone tomatidine, and (d) the activity increased as the number of sugars on the aglycone increased, but this was only statistically significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the alkaloids on tumor necrosis factor ? (TNF-?) was measured in RAW264.7 macrophage cells. There was a statistically significant negative correlation between the dosage of ?- and ?-tomatine and the level of TNF-?. ?-Tomatine was the most effective compound at reducing TNF-?. The dietary significance of the results and future research needs are discussed. PMID:22482398

Choi, Suk Hyun; Ahn, Jun-Bae; Kozukue, Nobuyuki; Kim, Hyun-Jeong; Nishitani, Yosuke; Zhang, Ling; Mizuno, Masashi; Levin, Carol E; Friedman, Mendel

2012-04-18

260

Enhanced antitumor activity of trastuzumab emtansine (T-DM1) in combination with pertuzumab in a HER2-positive gastric cancer model.  

PubMed

Human epidermal growth factor receptor 2 (HER2)-targeted therapy by trastuzumab has become increasingly important for treating HER2-positive cancers, and trastuzumab emtansine (T-DM1) is expected to serve as an effective alternative to trastuzumab. Pertuzumab, a HER2 dimerization inhibitor, showed prolonged progression-free survival when used with trastuzumab for HER2-positive breast cancer. In this study, we investigated the effect of combining T-DM1 and pertuzumab on xenografted gastric tumors. T-DM1 as a single agent showed significant antitumor activity in all the three HER2-high expression tumor models tested (NCI-N87, SCH and 4-1ST) but was ineffective against two HER2-low expression tumors (SNU-16 and MKN-28). Using the T-DM1-sensitive NCI-N87 model, the combination efficacy of T-DM1 and pertuzumab was elucidated. The combination induced significant tumor regression, whereas T-DM1 or pertuzumab alone did not. In cultured NCI-N87 cells stimulated with epidermal growth factor (EGF) or heregulin-?, concomitant treatment of T-DM1 and pertuzumab significantly inhibited proliferation and increased caspase 3/7 activity compared to either agent alone. Only the combination significantly inhibited the phosphorylation of EGFR or HER3, and its downstream factor AKT. Suppressed HER3 phosphorylation by the combination was also seen in the NCI-N87 xenografted tumors. Compared to single agent treatments, the combination treatment significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) against NCI-N87 cells. These findings suggest that T-DM1 in combination with pertuzumab shows significant antitumor activity by increasing AKT signal inhibition and ADCC in HER2-positive gastric cancers. PMID:23783223

Yamashita-Kashima, Yoriko; Shu, Sei; Harada, Naoki; Fujimoto-Ouchi, Kaori

2013-09-01

261

Gastric function measurements in drug development  

PubMed Central

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.

Pohle, Thorsten; Domschke, Wolfram

2003-01-01

262

Targeting receptor tyrosine kinases in gastric cancer  

PubMed Central

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.

Morishita, Asahiro; Gong, Jian; Masaki, Tsutomu

2014-01-01

263

Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia\\/reperfusion in rats  

Microsoft Academic Search

Ischaemia\\/reperfusion (I\\/R) induced gastric lesion, is known to be linked with free radical (FR) formation. Therefore, this model was used to assess the antioxidant effects of Nigella sativa oil (N.O) and thymoquinone (TQ) on gastric mucosal redox state and gastric lesions, 1 and 24 h after reperfusion. Male Wistar rats were subjected to I\\/R and were injected with either N.O

H. S El-Abhar; D. M Abdallah; S Saleh

2003-01-01

264

The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere  

PubMed Central

Introduction Activation of the PI3K/AKT pathway is a common phenomenon in cancer due to multiple mechanisms, including mutation of PI3KCA, loss or mutation of PTEN, or over-expression of receptor tyrosine kinases. We recently developed a novel AKT kinase inhibitor, AZD5363, and demonstrated that HGC27, a cell line harboring both PI3KCA mutation and PTEN loss, displayed the greatest sensitivity to this AKT inhibitor in vitro and in vivo. Case preparation To further elucidate the correlation between AZD5363 response and genetic alterations in gastric cancer (GC) and identify GC patients with both PI3KCA mutations and PTEN loss, we investigated the effects of pharmacological inhibition of AKT on a panel of 20 GC cell lines and genetic aberrations in tumor samples from a cohort of Chinese GC patients. We demonstrated that GC cells with PI3KCA mutations were selectively sensitive to AZD5363. Disease linkage studies showed that PI3KCA activating mutations or PTEN loss were found in 2.7% (4/150) and 23% (14/61) of Chinese GC patients respectively. To further dissect the role of PI3KCA mutation and PTEN loss in response to AKT inhibition, we tested the antitumor activity of AZD5363 in two patient-derived GC xenograft (PDGCX) models harboring either PI3KCA mutation or PTEN loss. Our data indicated that AZD5363 monotherapy treatment led to a moderate response in the PI3KCA mutant PDGCX model. Whilst monotherapy AZD5363 or Taxotere were ineffective in the PTEN negative PDGCX model, significant anti-tumor activity was observed when AZD5363 was combined with Taxotere. Conclusion Our results indicated that PI3KCA mutation is an important determinant of response to AKT inhibition in GC and combination with AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model. It is suggested that AKT inhibitor is an attractive option for treatment of a new segment of GC patients with aberrant PI3K/AKT signaling.

2013-01-01

265

Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons  

PubMed Central

Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ?50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9?min; remaining cells displayed only a decrease in mEPSC frequency. The late-phase decrease in mEPSC frequency was mimicked by the cannabinoid receptor agonists anandamide (AEA) and WIN 55,212-2, and it was blocked by the CB1 receptor antagonist AM251. The biphasic DEX effect was mimicked by AEA. The early increase in mEPSCs was mimicked by activation of transient receptor potential vanilloid type 1 (TRPV1) receptors with capsaicin and by activation of TRPV4 receptors with 4-?-PDD. The increase was reduced, but not blocked, by selective TRPV1 antagonists and in TRPV1 knockout mice; it was blocked completely by the broad-spectrum TRPV antagonist ruthenium red and by combined application of selective TRPV1 and TRPV4 antagonists. The DEX effects were prevented entirely by intracellular infusion of the G-protein inhibitor, GDP?S. Thus, DEX biphasically modulates synaptic glutamate onto a subset of gastric-related PVN neurons, which is likely mediated by induction of a retrograde messenger. The effect includes a TRPV1/4 receptor-mediated transient increase and subsequent CB1 receptor-mediated suppression of glutamate release. Multiphasic modulation of glutamate input to PVN neurons represents a previously unappreciated complexity of control of autonomic output by glucocorticoids and endogenous cannabinoids.

Boychuk, Carie R.; Zsombok, Andrea; Tasker, Jeffrey G.; Smith, Bret N.

2013-01-01

266

Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons.  

PubMed

Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ?50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9?min; remaining cells displayed only a decrease in mEPSC frequency. The late-phase decrease in mEPSC frequency was mimicked by the cannabinoid receptor agonists anandamide (AEA) and WIN 55,212-2, and it was blocked by the CB1 receptor antagonist AM251. The biphasic DEX effect was mimicked by AEA. The early increase in mEPSCs was mimicked by activation of transient receptor potential vanilloid type 1 (TRPV1) receptors with capsaicin and by activation of TRPV4 receptors with 4-?-PDD. The increase was reduced, but not blocked, by selective TRPV1 antagonists and in TRPV1 knockout mice; it was blocked completely by the broad-spectrum TRPV antagonist ruthenium red and by combined application of selective TRPV1 and TRPV4 antagonists. The DEX effects were prevented entirely by intracellular infusion of the G-protein inhibitor, GDP?S. Thus, DEX biphasically modulates synaptic glutamate onto a subset of gastric-related PVN neurons, which is likely mediated by induction of a retrograde messenger. The effect includes a TRPV1/4 receptor-mediated transient increase and subsequent CB1 receptor-mediated suppression of glutamate release. Multiphasic modulation of glutamate input to PVN neurons represents a previously unappreciated complexity of control of autonomic output by glucocorticoids and endogenous cannabinoids. PMID:23386808

Boychuk, Carie R; Zsombok, Andrea; Tasker, Jeffrey G; Smith, Bret N

2013-01-01

267

A novel PP2A enhancer induces caspase-independent apoptosis of MKN28 gastric cancer cells with high MEK activity.  

PubMed

The newly synthesized phosphatidylinositol (PI) derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol (diDCP-LA-PI) significantly enhanced protein phosphatase 2A (PP2A) activity in the cell-free assay. This prompted to assess the antitumor effect of diDCP-LA-PI. diDCP-LA-PI attenuated phosphorylation of mitogen-activated protein kinase (MAPK) kinase (MEK) in Lu65 human lung cancer and MKN28 human gastric cancer cells with high MEK activity. diDCP-LA-PI reduced cell viability in Lu65 and MKN28 cells, but otherwise such effect was not found in 786-O human renal cancer and HUH-7 human hepatoma cells with relatively low MEK activity. For Lu65 and MKN28 cells diDCP-LA-PI increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, but no significant activation of caspase-3, -8, or -9 was obtained. For MKN28 cells diDCP-LA-PI-induced reduction of MEK phosphorylation and cell viability was prevented by knocking-down PP2Ac. Taken together, these results indicate that diDCP-LA-PI induces caspase-independent apoptosis of Lu65 and MKN28 human cancer cells, for the latter cells by suppressing MEK activity through PP2A-catalyzed dephosphorylation. PMID:24508028

Tsuchiya, Ayako; Kanno, Takeshi; Shimizu, Tadashi; Nakao, Syuhei; Tanaka, Akito; Tabata, Chiharu; Nakano, Takashi; Nishizaki, Tomoyuki

2014-05-28

268

Influence of experimental hypokinesia on gastric secretory function  

NASA Technical Reports Server (NTRS)

The gastric secretory function of rats was studied in 4, 8, 16 and 30 day hypokinesia. Inhibition of both the gastric juice secretory and acid producing functions was found. The greatest inhibition was observed on day 8 of limited mobility. By days 16 and 30 of the experiment, a tendency of the gastric secretory activity to return to normal was observed, although it remained reduced.

Markova, O. O.; Vavryshchuk, V. I.; Rozvodovskyy, V. I.; Proshcheruk, V. A.

1980-01-01

269

Management of gastric adenocarcinoma  

Microsoft Academic Search

Gastric adenocarcinoma is the second most common cause of cancer death worldwide. The prognosis for patients with gastric\\u000a adenocarcinoma depends on the stage of the disease at the time of diagnosis and treatment. Early gastric cancer, limited to\\u000a the mucosa and submucosa, is best treated surgically and has a five-year survival rate of 70–95%. Surgical resection remains\\u000a the primary curative

P. Khosravi Shahi; V. M. Díaz Muñoz de la Espada; P. García Alfonso; S. Encina García; Y. Izarzugaza Perón; J. L. Arranz Cozar; B. Hernández Marín; G. Pérez Manga

2007-01-01

270

Laparoscopic adjustable gastric banding  

Microsoft Academic Search

Summary  \\u000a Background: A body mass index (BMI) of 40 or above represents clinically severe obesity, and warrants operative treatment, if requested\\u000a to bariatric surgery. The Adjustable Silicone Gastric Banding (Lap-Band, Bioenterics) and the Swedish Adjustable Gastric\\u000a Band (SAGB, Obtech) are recently produced laparoscopic gastric restrictive procedures. The aim of this study was to assess\\u000a all the possible complications linked to

K. Miller; E. Hell

1999-01-01

271

Update on gastric varices  

PubMed Central

Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding remains a serious complication of portal hypertension, with a high associated mortality. In this review we provide an update on the aetiology, classification and management of gastric varices, including acute bleeding, prevention of rebleeding and primary prophylaxis. We describe the optimum management strategies for gastric varices including drug, endoscopic and radiological therapies, focusing on recent published evidence.

Triantafyllou, Maria; Stanley, Adrian J

2014-01-01

272

A Novel Functional TagSNP Rs7560488 in the DNMT3A1 Promoter Is Associated with Susceptibility to Gastric Cancer by Modulating Promoter Activity  

PubMed Central

DNA-methyltransferase (DNMT)-3A which contains DNMT3A1 and DNMT3A2 isoforms have been suggested to play a crucial role in carcinogenesis and showed aberrant expression in most cancers. Accumulated evidences also indicated that single nucleotide polymorphisms (SNP) in DNMT genes were associated with susceptibility to different tumors. We hypothesized that genetic variants in DNMT3A1 promoter region are associated with gastric cancer risk. We selected the tagSNPs from the HapMap database for the Chinese and genotyped in a case-control study to evaluate the association with gastric cancer (GC) in a Chinese population. We identified that the functional tagSNP rs7560488 T>C associated with a significantly increased risk of GC. In vitro functional analysis by luciferase reporter assay and EMSA indicated that the tagSNP rs7560488 T>C substantially altered transcriptional activity of DNMT3A1 gene via influencing the binding of some transcriptional factors, although a definite transcriptional factor remains to be established. Compared with TT homozygotes, subjects who were TC heterozygotes and CC homozygotes exhibited a reduced expression of DNMT3A1. Furthermore, stratified analysis showed that individuals who harbor TC or CC genotypes less than 60 years old were more susceptible to GC. Our results suggest that the genetic variations in the DNMT3A1 promoter contribute to the susceptibility to GC and also provide an insight that tagSNP rs7560488 T>C may be a promising biomarker for predicting GC genetic susceptibility and a valuable information in GC pathogenesis.

Gong, Pihai; Qiao, Fengchang; Wang, Ling; Cui, He; Sui, Xinyuan; Gao, Jifan; Fan, Hong

2014-01-01

273

Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer.  

PubMed

Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has been shown to be a promising treatment strategy for peritoneal metastasis. The present study focused on the comparative evaluation of the therapeutic efficacy of nanoparticle albumin-bound PTX (Nab-PTX) and i.p. administration of the conventional solvent-based PTX (Sb-PTX). We also investigated the difference in antitumor activity depending on the route of administration in the Nab-PTX treatment. Nab-PTX was administered i.p. or intravenously (i.v.) and Sb-PTX was administered i.p. at equitoxic and equal doses to nude mice bearing gastric cancer OCUM-2MD3 cell subcutaneous and peritoneal xenografts. Therapeutic efficacy of Sb-PTX and Nab-PTX was evaluated as inhibition of tumor growth using a peritoneal metastatic model with subcutaneous xenografts. The survival rate was also investigated using mouse peritoneal models. For assessment of subcutaneous tumors, the change in tumor volume was measured, and for assessment of peritoneal tumors, the weight of ascitic fluid and the total peritoneal tumor burden were measured for each individual mouse. At equitoxic doses, treatment with Nab-PTX resulted in a greater reduction in the size of subcutaneous tumors and the weight of ascites and peritoneal burden as compared with i.p. Sb-PTX (p<0.05). Treatment with i.p. and i.v. Nab-PTX also achieved greater survival benefit than i.p. Sb-PTX (p<0.05). In contrast, there was no significant difference in the degree of tumor reduction and the survival time between both drugs at equal doses. With regard to the route of administration, the antitumor efficacy of Nab-PTX after i.v. administration was equivalent to the efficacy after i.p. administration. These results suggest that i.v. Nab-PTX may be another encouraging treatment option that can target peritoneal dissemination in gastric cancer. PMID:24859429

Kinoshita, Jun; Fushida, Sachio; Tsukada, Tomoya; Oyama, Katsunobu; Watanabe, Toshihumi; Shoji, Masatoshi; Okamoto, Koichi; Nakanuma, Shinichi; Sakai, Seisho; Makino, Isamu; Furukawa, Hiroyuki; Hayashi, Hironori; Nakamura, Keishi; Inokuchi, Masahumi; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Ninomiya, Itasu; Fujimura, Takashi; Masakazu, Yashiro; Hirakawa, Kosei; Ohta, Tetsuo

2014-07-01

274

Experimental Studies of Gastric Dysfunction in Motion Sickness: The Effect of Gastric and Vestibular Stimulation on the Vagal and Splanchnic Gastric Efferents.  

National Technical Information Service (NTIS)

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 ...

A. Niijima Z. Y. Jiang N. G. Daunton R. A. Fox

1991-01-01

275

Angiotensin II promotes the progression of human gastric cancer.  

PubMed

The renin-angiotensin system (RAS) plays an important role in cardiovascular homeostasis, carcinogenesis?related angiogenesis and cell proliferation. The present study was undertaken to determine the expression of angiotensin (Ang) II, Ang II type 1 and 2 receptors (AT1R and AT2R), and the activity of the angiotensin?converting enzyme (ACE) in gastric cancer tissue. The study further examined the roles of Ang II in the growth of gastric cancer cells in nude mice and in the migration and proliferation of MKN45 human gastric cancer cells. Gastric cancer tissue samples were obtained from gastric cancer patients. The levels of Ang II, AT1R and AT2R, as well as ACE activity were increased in tissues from gastric cancer patients compared to healthy tissues. A gastric cancer model was established by intraperitoneally injecting MKN45 human gastric cancer cells in nude mice, intraperitoneally injecting Ang II and measuring the tumor size every two days. Ang II treatment caused an increase in the size and weight of the tumor mass in nude mice, whereas the AT1R antagonist losartan significantly inhibited the size and weight of the tumor. While Ang II enhanced the migratory and proliferative rate of MKN45 human gastric cancer cells, these were significantly reduced following treatment with losartan. These results indicate that RAS is activated in gastric cancer patients and Ang II promotes the progression of gastric cancer in nude mice, as well as the migration and proliferation of MKN45 human gastric cancer cells. PMID:24424956

Huang, Ming-Min; Guo, Ai-Bin; Sun, Jun-Feng; Chen, Xiao-Lin; Yin, Zhen-Yu

2014-03-01

276

CADPE inhibits PMA-stimulated gastric carcinoma cell invasion and matrix metalloproteinase-9 expression by FAK/MEK/ERK-mediated AP-1 activation.  

PubMed

Metastasis is one of the main causes of death for patients with malignant tumors. Aberrant expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Here, we found that caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) could inhibit the migration and invasion of human gastric carcinoma cells in Transwell migration assays. To understand the underlying mechanism, we showed that CADPE significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced increases in MMP-9 expression and activity in a dose-dependent manner. The inhibitory effect of CADPE on MMP-9 expression correlated well with the suppression of MMP-9 promoter activity and the reduction of MMP-9 mRNA. Reporter gene assay and electrophoretic mobility shift assay showed that CADPE inhibited MMP-9 expression by suppressing the activation of the nuclear transcription factor activator protein-1 (AP-1) and c-Fos, but not NF-?B. Moreover, CADPE inhibited PMA-induced phosphorylation of protein kinases involved in AP-1 activation, such as focal adhesion kinase (FAK), mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK), and ERK1/2, whereas CADPE had little effect on the phosphorylation of p38 and c-jun NH(2)-terminal kinase. Taken together, our findings indicate that CADPE could be a unique antitumor agent that specifically inhibits MMP-9 activity by targeting the activation of FAK/MEK/ERK protein kinases and AP-1 transcription factor. PMID:21047770

Han, Honghui; Du, Bing; Pan, Xinhua; Liu, Junchen; Zhao, Qufei; Lian, Xiaoyuan; Qian, Min; Liu, Mingyao

2010-11-01

277

Vection-induced gastric dysrhythmias and motion sickness  

NASA Technical Reports Server (NTRS)

Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects.

Koch, K. L.; Stern, R. M.

1986-01-01

278

Human Primary Gastric Dendritic Cells Induce a Th1 Response to H. pylori  

PubMed Central

Adaptive CD4 T-cell responses are important in the pathogenesis of chronic Helicobacter pylori gastritis. However, the gastric antigen-presenting cells that induce these responses have not yet been identified. Here we show that dendritic cells (DCs) are present in the gastric mucosa of healthy subjects but are more prevalent and more activated in the gastric mucosa of H. pylori -infected subjects. H. pylori induced gastric DCs isolated from noninfected subjects to express increased levels of CD11c, CD86 and CD83, and to secrete proinflammatory cytokines, particularly interleukin (IL)-6 and IL-8. Importantly, gastric DCs pulsed with live H. pylori, but not control DCs, mediated T-cell secretion of interferon-?. The ability of H. pylori to induce gastric DC maturation and stimulate gastric DC activation of Th1 cells implicates gastric DCs as initiators of the immune response to H. pylori.

Bimczok, D; Clements, RH; Waites, KB; Novak, L; Eckhoff, DE; Mannon, PJ; Smith, PD; Smythies, LE

2013-01-01

279

Continent gastric pouch  

Microsoft Academic Search

Between January 1985 and June 1995 a total of 12 patients (9 female, 3 male) underwent total reconstruction of the lower urinary tract using gastric tissue. Their mean age was 10 years (range, 5–25 years). Total gastric bladder substitution was performed in seven patients, whereas five other patients had composite continent reservoirs (stomach plus bowel) created. The diagnoses were cloacal

M. C. Carr; M. E. Mitchell

1996-01-01

280

Epidemiology of gastric cancer  

PubMed Central

The incidence and mortality of gastric cancer have fallen dramatically in US and elsewhere over the past several decades. Nonetheless, gastric cancer remains a major public health issue as the fourth most common cancer and the second leading cause of cancer death worldwide. Demographic trends differ by tumor location and histology. While there has been a marked decline in distal, intestinal type gastric cancers, the incidence of proximal, diffuse type adenocarcinomas of the gastric cardia has been increasing, particularly in the Western countries. Incidence by tumor sub-site also varies widely based on geographic location, race, and socio-economic status. Distal gastric cancer predominates in developing countries, among blacks, and in lower socio-economic groups, whereas proximal tumors are more common in developed countries, among whites, and in higher socio-economic classes. Diverging trends in the incidence of gastric cancer by tumor location suggest that they may represent two diseases with different etiologies. The main risk factors for distal gastric cancer include Helicobacter pylori (H pylori) infection and dietary factors, whereas gastroesophageal reflux disease and obesity play important roles in the development of proximal stomach cancer. The purpose of this review is to examine the epidemiology and risk factors of gastric cancer, and to discuss strategies for primary prevention.

Crew, Katherine D; Neugut, Alfred I

2006-01-01

281

Activation of p38 MAPK through transient receptor potential A1 in a rat model of gastric distension-induced visceral pain.  

PubMed

Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. We reported previously that the activation of ERK1/2, a member of the mitogen-activated protein kinase (MAPK) family, in primary sensory neurons was involved in acute visceral pain. Moreover, we also revealed that this activation of ERK1/2 occurred through transient receptor potential (TRP) A1, a member of the TRP family of ion channels. In contrast, it is known that the activation of p38 MAPK (p38) contributes to the development and maintenance of inflammatory and neuropathic pain. On the basis of these results, the aim of this study was to investigate the involvement of p38 and TRPA1 in acute visceral pain. Male Sprague-Dawley rats were used. Electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. We then examined the phosphorylated-p38 (p-p38) labeling in the dorsal root ganglion (DRG) after GD using immunohistochemistry. Noxious GD induced p-p38 in DRG neurons with a peak at 2 min after GD. We also found a stimulus intensity-dependent increase in the number of p-p38-immunoreactive neurons in the DRG. Intrathecal administration of the p38 inhibitor, SB203580, attenuated the electromyographic response to noxious GD. Furthermore, intrathecal administration of TRPA1 antisense oligodeoxynucleotide decreased the p38 activation in DRG neurons. The activation of p38 pathways in DRG neurons by noxious GD may be correlated with the activation state of the primary afferent neurons through TRPA1, and further, involved in the development of visceral pain. PMID:23222658

Kondo, Takashi; Sakurai, Jun; Miwa, Hiroto; Noguchi, Koichi

2013-01-23

282

Treatment of gastric cancer  

PubMed Central

The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status

Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; Mabilia, Andrea; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

2014-01-01

283

Large gastric lipoma.  

PubMed

Gastric lipoma is a rare benign tumor and seen in five percent of gastro-intestinal lipomas and accounts for less than one percent of all gastric tumors. Gastric lipomas are located submucosally and usually in antral region of Stomach. Computed tomography is considered as valuable tool in the diagnosis of gastrointestinal lipomas. Due to their relative rarity, gastric lipomas are often left out of the differential diagnosis for upper gastro-intestinal submucosal masses. We report a case of 70 year female that presented with upper abdominal pain since last two years. Abdominal Computed tomography revealed a large gastric lipoma in antral region. Patient refused for any surgical intervention due to old age. Patient was provided symptomatic treatment and was under regular followup. PMID:23434967

Sharma, B K; Dhakal, O P

2012-01-01

284

Evaluation of antitumour effects of docetaxel (Taxotere®) on human gastric cancers In vitro and In vivo  

Microsoft Academic Search

In vitro antitumour effects of docetaxel (Taxotere®) were examined in nine cultured human gastric cancer cell lines and 18 clinical gastric cancer specimens. In vivo antitumour effects were examined in human gastric cancer xenografts in nude mice. The activity was compared with paclitaxel (Taxol®). Docetaxel was more effective than paclitaxel in six of the nine cell lines and the effectiveness

M. Tanaka; T. Obata; T. Sasaki

1996-01-01

285

Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer  

Microsoft Academic Search

Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial.

S-H Lee; W K Kang; H Y Kim; J H Kim; S I Lee; J O Park; K Kim; C W Jung; Y S Park; Y-H Im; M H Lee

2004-01-01

286

Significance of gastric mucosal pepsinogen and plasma corticosteroid levels in the course of cinchophen ulceration  

Microsoft Academic Search

Summary  The results reported here have compelling implications concerning gastric mucosal damage in detecting the mechanism of cinchophen-induced\\u000a gastric lesions in dogs. The acute type of cinchophen gastric lesion, a condition characterized by bleeding and\\/or diffuse\\u000a superficial gastric erosions of the fundic gland area, is indicative of so called “stress ulceration” and may be due to activating\\u000a intramucosal pepsinogen during a

Yukio Nagamachi

1977-01-01

287

Clot lysis by gastric juice: an in vitro study  

Microsoft Academic Search

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found

S E Patchett; H Enright; N Afdhal; W OConnell; D P ODonoghue

1989-01-01

288

Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma.  

PubMed

Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis. PMID:8801193

Cahill, R J; Kilgallen, C; Beattie, S; Hamilton, H; O'Morain, C

1996-02-01

289

Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma.  

PubMed Central

Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis.

Cahill, R J; Kilgallen, C; Beattie, S; Hamilton, H; O'Morain, C

1996-01-01

290

Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP  

Microsoft Academic Search

Aims\\/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (cAMP) production was assessed in Chinese hamster lung fibroblast

F. P. M. O'Harte; V. A. Gault; J. C. Parker; P. Harriott; M. H. Mooney; C. J. Bailey; P. R. Flatt

2002-01-01

291

Gastric Bypass Operation for Obesity  

Microsoft Academic Search

. Gastric bypass is considered by many to be the gold standard for surgical treatment of obesity. Gastric bypass was\\u000a a natural evolution from gastric operations that were used for the treatment of peptic ulcer disease. Gastric bypass, first\\u000a described in 1967, has undergone many modifications. It presently exists as a hybrid operation. Gastric bypass operation has\\u000a been extensively scrutinized

Mathias A. L. Fobi; Hoil Lee; Ronald Holness; DeGaulle Cabinda

1998-01-01

292

Additive effects of EGF and IL-1? regulate tumor cell migration and invasion in gastric adenocarcinoma via activation of ERK1/2.  

PubMed

Growth and inflammatory factors are associated with poor prognosis in gastric adenocarcinoma (GA); however, the additive effects of growth and inflammatory factors in GA remain unclear. In this study, we investigated the ability of epidermal growth factor (EGF) and interleukin (IL?1?) to activate extracellular signal-regulated kinase (ERK)1/2 in GA cells, and correlated the relationships between their roles with the metastatic potential both in GA cells and GA tissues. The effects of EGF, IL-1? and EGF plus IL-1? in AGS and MKN-45 GA cells were examined using western blotting, Transwell migration and invasion assays, immunocytochemical staining and an activator protein (AP)-1 luciferase reporter gene assay, and was further characterized in GA tissues by immunohistochemistry. The results exhibited that EGF and IL-1? additively activated ERK1/2, increased migration and invasion than either EGF or IL-1? alone in AGS and MKN-45 cells. The mechanisms were involved in upregulating MMP-9 expression through increasing AP-1 transcriptional activity via ERK1/2 pathway; these effects were dose-dependently inhibited by silencing ERK1/2 or using U0126. In vivo data also confirmed that the overexpression of p-ERK1/2 in GA tissues correlated well with the EGF, IL-1?, EGF plus IL-1?, and was associated with metastasis, which was well correlation with the expression of MMP-9 and c-fos (AP-1). The results demonstrate that growth and inflammatory factors play an important role in metastasis of GA by additively activating ERK-1/2 and AP-1, and upregulating MMP-9. As both cytokines contribute to the migration and invasion of GA cells, EGF/IL-1?/ERK1/2 pathways may be key pathways closely associated with GA progression. PMID:24789460

Han, Junyong; Xie, Yanchuan; Lan, Fenghua; Yu, Yinghao; Liu, Wei; Chen, Jinhua; Zheng, Feng; Ouyang, Xuenong; Lin, Xiangquan; Lin, Yanhong; Huang, Qiaojia; Wang, Lie; Tan, Jianming

2014-07-01

293

Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901  

Microsoft Academic Search

We aimed to study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation, apoptosis, and autophagy in gastric cancer cell line SGC7901. In this study, we showed that LY294002 inhibited the viability of gastric cancer SGC7901 cells. We also showed that LY294002 increased the expression of microtubule- associated protein 1 light chain 3 (LC3), and

Chungen Xing; Baosong Zhu; Huihui Liu; Huihua Yao; Lifeng Zhang

2008-01-01

294

In Oesophageal Squamous Cells Exposed to Acidic Bile Salt Medium, Omeprazole Inhibits IL-8 Expression through Effects on Nuclear Factor-?B and Activator Protein-1  

PubMed Central

Objective Oesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPIs) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts. Design Human primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-?B and AP-1 subunits to the IL-8 promoter was assessed by ChIP assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system. Results Acidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-?B and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-?B subunit) and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration. Conclusions In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-?B and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognized PPI effects might contribute to the healing of reflux oesophagitis.

Huo, Xiaofang; Zhang, Xi; Yu, Chunhua; Zhang, Qiuyang; Cheng, Edaire; Wang, David H.; Pham, Thai H.; Spechler, Stuart J.; Souza, Rhonda F.

2013-01-01

295

Gastric mucosal nerve density  

PubMed Central

Background: Autonomic neuropathy is a frequent diagnosis for the gastrointestinal symptoms or postural hypotension experienced by patients with longstanding diabetes. However, neuropathologic evidence to substantiate the diagnosis is limited. We hypothesized that quantification of nerves in gastric mucosa would confirm the presence of autonomic neuropathy. Methods: Mucosal biopsies from the stomach antrum and fundus were obtained during endoscopy from 15 healthy controls and 13 type 1 diabetic candidates for pancreas transplantation who had secondary diabetic complications affecting the eyes, kidneys, and nerves, including a diagnosis of gastroparesis. Neurologic status was evaluated by neurologic examination, nerve conduction studies, and skin biopsy. Biopsies were processed to quantify gastric mucosal nerves and epidermal nerves. Results: Gastric mucosal nerves from diabetic subjects had reduced density and abnormal morphology compared to control subjects (p < 0.05). The horizontal and vertical meshwork pattern of nerve fibers that normally extends from the base of gastric glands to the basal lamina underlying the epithelial surface was deficient in diabetic subjects. Eleven of the 13 diabetic patients had residual food in the stomach after overnight fasting. Neurologic abnormalities on clinical examination were found in 12 of 13 diabetic subjects and nerve conduction studies were abnormal in all patients. The epidermal nerve fiber density was deficient in skin biopsies from diabetic subjects. Conclusions: In this observational study, gastric mucosal nerves were abnormal in patients with type 1 diabetes with secondary complications and clinical evidence of gastroparesis. Gastric mucosal biopsy is a safe, practical method for histologic diagnosis of gastric autonomic neuropathy.

Selim, M.M.; Wendelschafer-Crabb, G.; Redmon, J.B.; Khoruts, A.; Hodges, J.S.; Koch, K.; Walk, D.; Kennedy, W.R.

2010-01-01

296

Biomagnetic characterization of spatiotemporal parameters of the gastric slow wave.  

PubMed

Certain gastric disorders affect spatiotemporal parameters of the gastric slow wave. Whereas the electrogastrogram (EGG) evaluates electric potentials to determine primarily temporal parameters, fundamental physical limitations imposed by the volume conduction properties of the abdomen suggest the evaluation of gastric magnetic fields. We used a multichannel superconducting quantum interference device magnetometer to study the magnetogastrogram (MGG) in 20 normal human subjects before and after a test meal. We computed the frequency and amplitude parameters of the gastric slow wave from MGG. We identified normal gastric slow wave activity with a frequency of 2.6 +/- 0.5 cycles per minute (cpm) preprandial and 2.8 +/- 0.3 cpm postprandial. In addition to frequency and amplitude, the use of surface current density mapping applied to the multichannel MGG allowed us to visualize the propagating slow wave and compute its propagation velocity (6.6 +/- 1.0 mm s(-1) preprandial and 7.4 +/- 0.4 mm s(-1) postprandial). Whereas MGG and EGG signals exhibited strong correlation, there was very little correlation between the MGG and manometry. The MGG not only records frequency dynamics of the gastric slow wave, but also characterizes gastric propagation. The MGG primarily reflects the underlying gastric electrical activity, but not its mechanical activity. PMID:16918726

Bradshaw, L A; Irimia, A; Sims, J A; Gallucci, M R; Palmer, R L; Richards, W O

2006-08-01

297

IL-1?-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9  

PubMed Central

Background Interleukin-1? (IL-1?) has been implicated in the progression of gastric adenocarcinoma (GA); however, the molecular mechanisms of action of IL-1? in GA are poorly characterized. P38 and JNK are the major MAPK family members that regulate IL-1? signaling pathways. Here, we investigated the role of both p38 and JNK in IL-1?-induced GA cell migration, invasion and metastatic potential. Methods The effects of IL-1?-induced p38 and JNK activation in GA cells were determined using in vitro Transwell migration and invasion assays of MKN-45 and AGS cells, or an in vivo metastasis assay in nude mice. The IL-1?-induced p38 signaling pathway was further characterized in GA cells. Activation of the IL-1?/p38 signaling pathway was also assessed in human primary GA tissues by immunohistochemistry. Results IL-1?-induced activation of p38 increased GA cell migration and invasion in vitro and promoted the metastatic potential of GA cells in vivo; these effects were attenuated by p38 siRNA or the p38 inhibitor SB202190. MMP2 or MMP9 siRNAs and the MMP2/9 inhibitor BiPS also inhibited IL-1?-induced GA cell migration and invasion in vitro. IL-1?-induced p38 activation significantly increased MMP2 and MMP9 mRNA and protein expression and activity. Luciferase reporter assays demonstrated that the activator protein-1 (AP-1) and the AP-1 binding sites of the MMP9 promoter (?670/MMP9) were activated by IL-1?-induced p38 activation. Phospho-p38 was significantly upregulated in human GA tissues (compared to matched non-neoplastic tissues), and significantly associated with lymph node metastasis, and invasion beyond the serosa. Expression of phospho-p38 significantly correlated with IL-1?, MMP2, MMP9, and c-fos expression in both human GA tissues and GA cell metastases in the lungs of nude mice. IL-1? was also capable of activating JNK in GA cells, but activation of JNK was not associated with GA cell migration and invasion. Therefore, IL-1?-induced the migration and invasion in GA cells were regulated by p38, but not by JNK. Conclusions IL-1?-induced p38 activation and the IL-1?/p38/AP-1(c-fos)/MMP2 & MMP9 pathway play an important role in metastasis in GA; this pathway may provide a novel therapeutic target for GA.

2014-01-01

298

Small molecule R1498 as a well-tolerated and orally active kinase inhibitor for hepatocellular carcinoma and gastric cancer treatment via targeting angiogenesis and mitosis pathways.  

PubMed

Protein kinases play important roles in tumor development and progression. Lots of kinase inhibitors have entered into market and show promising clinical benefits. Here we report the discovery of a novel small molecule, well-tolerated, orally active kinase inhibitor, R1498, majorly targeting both angiogenic and mitotic pathways for the treatment of hepatocellular carcinoma (HCC) and gastric cancer (GC). A series of biochemical and cell-based assays indicated that the target kinase cluster of R1498 included Aurora kinases and VEGFR2 et al. R1498 showed moderate in vitro growth inhibition on a panel of tumor cells with IC50 of micromole range. The in vivo anti-tumor efficacy of R1498 was evaluated on a panel of GC and HCC xenografts in a parallel comparison with another multikinase inhibitor sorafenib. R1498 demonstrated superior efficacy and toxicity profile over sorafenib in all test models with >80% tumor growth inhibition and tumor regression in some xenogratfts. The therapeutic potential of R1498 was also highlighted by its efficacy on three human GC primary tumor derived xenograft models with 10-30% tumor regression rate. R1498 was shown to actively inhibit the Aurora A activity in vivo, and decrease the vascularization in tumors. Furthermore, R1498 presented good in vivo exposure and therapeutic window in the pharmacokinetic and dose range finding studies. Theses evidences indicate that R1498 is a potent, well-tolerated, orally active multitarget kinase inhibitor with a unique antiangiogenic and antiproliferative profile, and provide strong confidence for further development for HCC and GC therapy. PMID:23755206

Zhang, Chao; Wu, Xihan; Zhang, Meifang; Zhu, Liangcheng; Zhao, Rong; Xu, Danqing; Lin, Zhaohu; Liang, Chungen; Chen, Taiping; Chen, Li; Ren, Yi; Zhang, Joe; Qin, Ning; Zhang, Xiongwen

2013-01-01

299

Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and {beta}-adrenergic receptor signaling pathways  

SciTech Connect

Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor ({alpha}7 nAChR) and {beta}-adrenergic receptors. Treatment of cells with {alpha}-bungarotoxin ({alpha}-BTX, {alpha}7nAChR antagonist) or propranolol ({beta}-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE{sub 2} and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE{sub 2} induction can only be suppressed by propranolol, but not {alpha}-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis.

Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.; Yu Jun; Leung, W.K. [Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong (Hong Kong); Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong (Hong Kong); Cho, C.H. [Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong (Hong Kong); Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong (Hong Kong); Sung, J.J.Y. [Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong (Hong Kong); Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR (Hong Kong)], E-mail: joesung@cuhk.edu.hku

2008-12-01

300

Dietary monosodium glutamate enhances gastric secretion.  

PubMed

Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT(3) receptors in the gastric mucosa. PMID:20224184

Khropycheva, Raisa; Uneyama, Hisayuki; Torii, Kunio; Zolotarev, Vasiliy

2009-01-01

301

[Gastric proton pump: genes and their expression].  

PubMed

The gastric proton pump (H+/K(+)-ATPase) is a typical P-type ATPase consisting of the alpha and beta subunits and secreting acid into stomach. This enzyme is similar to Na+/K(+)-ATPase in primary structure and gene organization. The exon/intron organizations of the genes for the two subunits of H+/K(+)-ATPase are highly similar to those of the corresponding subunits of Na+/K(+)-ATPase. In contrast to Na+/K(+)-ATPase subunits, alpha and beta subunits of H+/K(+)-ATPase are expressed specifically in gastric parietal cells. Consistently, a sequence motif [(G/C)PuPu(G/C)NGAT(A/T)PuPy] in the 5'upstream regions of the H+/K(+)-ATPase subunit genes was recognized by the gastric mucosal nuclear protein(s). We found that two novel zinc-finger proteins (GATA-GT1 and GATA-GT2) are present in the gastric parietal cells and bind to this motif. These proteins activate the transcription of the reporter gene connected with the 5'-upstream regions of the H+/K(+)-ATPase subunit genes. These results suggest that gastric GATA-DNA binding proteins have roles in activating transcription of H+/K(+)-ATPase genes in parietal cells. PMID:8920687

Futai, M

1996-04-01

302

Gallic acid inhibits gastric cancer cells metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity  

SciTech Connect

Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-?B activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity. Thus, GA might be a potential agent in treating gastric cancer. Highlights: ? GA could downregulate AKT signal via increased expression of RhoB. ? GA inhibits metastasis in vitro in gastric carcinoma. ? GA inhibits tumor growth in nude mice model.

Ho, Hsieh-Hsun [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Chi-Sen [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan (China); Ho, Wei-Chi [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China)] [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China); Liao, Sheng-You [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Lin, Wea-Lung [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Wang, Chau-Jong, E-mail: wcj@csmu.edu.tw [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China) [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

2013-01-01

303

Occupation and gastric cancer  

PubMed Central

Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration.

Raj, A; Mayberry, J; Podas, T

2003-01-01

304

Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats.  

PubMed

The effects of acute systemic administration of duloxetine, amitriptyline, mirtazapine and fluoxetine were compared in experimental models of gastric ulcer in rats. Compared with the vehicle control group, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), mirtazapine (10 and 20 mg/kg, i.p.) and fluoxetine (5 and 10 mg/kg, i.p.) significantly protected against water-immersion plus restraint stress-induced gastric lesions, as evidenced by dose-dependent decrease in ulcer index and score for intraluminal bleeding. Duloxetine (20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), fluoxetine (10 and 20 mg/kg, i.p.) and mirtazapine (5, 10 and 20 mg/kg, i.p.) significantly decreased indomethacin (30 mg/kg, i.p.)-induced gastric lesions and intraluminal bleeding. In reserpine (25 mg/kg, i.p.)-induced gastric ulcer experiment, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (5, 10 and 20 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.) and mirtazapine (5 mg/kg, i.p.) significantly attenuated gastric lesions and intraluminal bleeding. These results (a) highlighted the relationship in correlating antiulcer effect of drugs from different antidepressant classes across various animal gastric ulcer models and (b) suggested that antidepressants that differently affected both norepinephrine and serotonin levels (such as duloxetine, amitriptyline and mirtazapine) had more potent and efficacious antiulcer effect in various gastric ulcer animal models than drugs that only affected serotonin level (such as fluoxetine). PMID:22789173

Ji, Cheng-Xue; Fan, Dong-Sheng; Li, Wei; Guo, Liang; Liang, Zi-Liang; Xu, Rui-Ming; Zhang, Jian-Jun

2012-09-15

305

Induction in gastric mucosal prostaglandin and nitric oxide by Helicobacter pylori is dependent on MAPK/ERK-mediated activation of IKK-? and cPLA2: modulatory effect of ghrelin.  

PubMed

Among the key factors defining the extent of gastric mucosal inflammatory involvement in response to Helicobacter pylori is the excessive generation of prostaglandin (PGE2) and nitric oxide (NO), caused by the overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and triggered by the activation of mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase, p38 and ERK, and nuclear translocation of the cognate transcription factors. In this study, we report on the role of MAPK/ERK in the regulation of H. pylori LPS-induced gastric mucosal expression of COX-2 and iNOS. We show that ERK activation by the LPS leads to phosphorylation of the inhibitory ?B kinase-? (IKK-?) and cytosolic phospholipase A2 (cPLA2), and is reflected in the upsurge in NF-?B nuclear translocation, induction in COX-2 and iNOS expression, and up-regulation in cPLA2 activity. The modulatory effect of peptide hormone, ghrelin, on the LPS-induced changes, although associated with further enhancement in ERK, IKK-?, and cPLA2 phosphorylation, was reflected in the suppression of IKK-? and cPLA2 activity through S-nitrosylation. While the effect of ghrelin on S-nitrosylation was susceptible to suppression by the inhibitors of Src/Akt pathway, the inhibition of ERK activation caused the blockage in IKK-? and cPLA2 phosphorylation as well as S-nitrosylation. Taken together, our data show that H. pylori-induced ERK activation plays a critical role in up-regulation of gastric mucosal PGE2 and NO generation at the level of IKK-? and cPLA2 activation, and that ghrelin counters these proinflammatory consequences of the LPS through Src/Akt-dependent S-nitrosylation. PMID:23563696

Slomiany, B L; Slomiany, A

2013-06-01

306

Neural mechanism of acupuncture-modulated gastric motility  

PubMed Central

AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism. METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed. RESULTS: Acupuncture-stimulation by exciting A? and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals. CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of A? and/or C afferent fibers can markedly modulate gastrointestinal motility.

Li, Yu-Qing; Zhu, Bing; Rong, Pei-Jing; Ben, Hui; Li, Yan-Hua

2007-01-01

307

Regulation of gastric hormones by systemic rapamycin  

PubMed Central

The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine kinase, is an intracellular fuel sensor critical for cellular energy homeostasis. Gastrointestinal endocrine cells play a vital role in the regulation of energy balance by secreting hormones that inform the brain about energy supply. Here we showed the localization of mTOR signaling molecules in more than 90 % of gastric ghrelin cells and 36 ± 3% of gastrin cells, while no somatostatin-positive cell showed phospho-S6K1 immunoreactivity. Inhibition of mTOR significantly stimulated expression of gastric ghrelin mRNA and protein, and the concentration of plasma ghrelin (2.06±0.34 vs. 12.53±3.9 ng/ml, p<0.05), inhibited gastrin synthesis and secretion (75.01±6.71 vs. 54.04±3.65 pg/ml, p<0.05), but had no effect on somatostatin production (165.2±25.07 vs. 178.9±29.14 pg/ml, p=0.73). Gastric mTOR is a gastric sensor whose activity is linked to the differential regulation of gastric hormone production and release.

Xu, Geyang; Li, Yin; An, Wenjiao; Zhao, Jing; Xiang, Xinxin; Ding, Li; Li, Ziru; Guan, Youfei; Wang, Xian; Tang, Chaoshu; Zhu, Yi; Wang, Nanping; Li, Xiaoying; Mulholland, Michael; Zhang, Weizhen

2010-01-01

308

Honey and apoptosis in human gastric mucosa.  

PubMed

Background: Gastric cancer is the fourth most common malignancy in the world. Honey is a complex mixture of special biological active constituents. Honey possesses antioxidant and antitumor properties. Nutritional studies have indicated that consumption of honey modulates the risk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisive role in precancerous changes. Our chief study was conducted to assess the relationship between consumption of honey and apoptosis in human gastric mucosa. Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred to two hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62 subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire (FFQ) and apoptosis was detected by TUNEL technique. We tested polynomial curve to find the best fit between honey consumption and apoptosis. Results: A positive relation between honey consumption and apoptosis was found (P=0.024). Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honey amount) - 0.533(honey amount)2 +1.833×10-5(honey amount)7. Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis in gastric mucosa. PMID:24688918

Ghaffari, Aida; Somi, Mohammad H; Safaiyan, Abdolrasoul; Modaresi, Jabiz; Ostadrahimi, Alireza

2012-01-01

309

Gastric adenocarcinoma presenting with gastric outlet obstruction in a child.  

PubMed

Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5?cm × 2?cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction. PMID:24707411

Al-Hussaini, Abdulrahman; Alghamdi, Salem; Alsaaran, Rasha; Al-Kasim, Fawaz; Habib, Zakaria; Ourfali, Nouri

2014-01-01

310

Gastric Adenocarcinoma Presenting with Gastric Outlet Obstruction in a Child  

PubMed Central

Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5?cm × 2?cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction.

Al-Hussaini, Abdulrahman; AlGhamdi, Salem; Al-Kasim, Fawaz; Habib, Zakaria; Ourfali, Nouri

2014-01-01

311

Role of Notch signaling pathway in gastric cancer pathogenesis.  

PubMed

Notch signaling pathway is activated dynamically during evolution playing significant role in cell fate determination and differentiation. It has been known that alterations of this pathway may lead to human malignancies, including gastric cancer. Despite a decline in the overall incidence, this disease still remains an important global health problem. Therefore, a better understanding of the molecular alterations underlying gastric cancer may contribute to the development of rationally designed molecular targeted therapies. It has been reported that Notch1 receptor could become a prognostic marker of gastric cancer and novel target for gastric cancer therapy. Among the novel and targeted approaches for the treatment of gastric cancer is also the process of Notch receptors regulation by specific microRNA. ?-secretase inhibitors are also taken into consideration. PMID:23788953

Brzozowa, Marlena; Miela?czyk, Lukasz; Michalski, Marek; Malinowski, Lukasz; Kowalczyk-Ziomek, Gra?yna; Helewski, Krzysztof; Harabin-S?owi?ska, Marzena; Wojnicz, Romuald

2013-01-01

312

Role of Notch signaling pathway in gastric cancer pathogenesis  

PubMed Central

Notch signaling pathway is activated dynamically during evolution playing significant role in cell fate determination and differentiation. It has been known that alterations of this pathway may lead to human malignancies, including gastric cancer. Despite a decline in the overall incidence, this disease still remains an important global health problem. Therefore, a better understanding of the molecular alterations underlying gastric cancer may contribute to the development of rationally designed molecular targeted therapies. It has been reported that Notch1 receptor could become a prognostic marker of gastric cancer and novel target for gastric cancer therapy. Among the novel and targeted approaches for the treatment of gastric cancer is also the process of Notch receptors regulation by specific microRNA. ?-secretase inhibitors are also taken into consideration.

Mielanczyk, Lukasz; Michalski, Marek; Malinowski, Lukasz; Kowalczyk-Ziomek, Grazyna; Helewski, Krzysztof; Harabin-Slowinska, Marzena; Wojnicz, Romuald

2013-01-01

313

A review on gastric leptin: the exocrine secretion of a gastric hormone  

PubMed Central

A major advance in the understanding of the regulation of food intake has been the discovery of the adipokine leptin a hormone secreted by the adipose tissue. After crossing the blood-brain barrier, leptin reaches its main site of action at the level of the hypothalamic cells where it plays fundamental roles in the control of appetite and in the regulation of energy expenditure. At first considered as a hormone specific to the white adipose tissue, it was rapidly found to be expressed by other tissues. Among these, the gastric mucosa has been demonstrated to secrete large amounts of leptin. Secretion of leptin by the gastric chief cells was found to be an exocrine secretion. Leptin is secreted towards the gastric lumen into the gastric juice. We found that while secretion of leptin by the white adipose tissue is constitutive, secretion by the gastric cells is a regulated one responding very rapidly to secretory stimuli such as food intake. Exocrine-secreted leptin survives the hydrolytic conditions of the gastric juice by forming a complex with its soluble receptor. This soluble receptor is synthesized by the gastric cells and the leptin-leptin receptor complex gets formed at the level of the gastric chief cell secretory granules before being released into the gastric lumen. The leptin-leptin receptor upon resisting the hydrolytic conditions of the gastric juice is channelled, to the duodenum. Transmembrane leptin receptors expressed at the luminal membrane of the duodenal enterocytes interact with the luminal leptin. Leptin is actively transcytosed by the duodenal enterocytes. From the apical membrane it is transferred to the Golgi apparatus where it binds again its soluble receptor. The newly formed leptin-leptin receptor complex is then secreted baso-laterally into the intestinal mucosa to reach the blood capillaries and circulation thus reaching the hypothalamus where its action regulates food intake. Exocrine-secreted gastric leptin participates in the short term regulation of food intake independently from that secreted by the adipose tissue. Adipose tissue leptin on the other hand, regulates in the long term energy storage. Both tissues work in tandem to ensure management of food intake and energy expenditure.

Cammisotto, Philippe

2012-01-01

314

Endoscopic treatment for early gastric cancer  

PubMed Central

Gastric cancer remains one of the most common causes of cancer death. However the proportion of early gastric cancer (EGC) at diagnosis is increasing. Endoscopic treatment for EGC is actively performed worldwide in cases meeting specific criteria. Endoscopic mucosal resection can treat EGC with comparable results to surgery for selected cases. Endoscopic submucosal dissection (ESD) increases the en bloc and complete resection rates and reduces the local recurrence rate. ESD has been performed with expanded indication and is expected to be more widely used in the treatment of EGC through the technological advances in the near future. This review will describe the techniques, indications and outcomes of endoscopic treatment for EGC.

Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J.

2014-01-01

315

Gastric volvulus with partial and complete gastric necrosis  

PubMed Central

Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature.

Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

2014-01-01

316

Congenital gastric teratoma with gastric perforation mimicking meconium peritonitis.  

PubMed

A case of congenital immature gastric teratoma along with spontaneous gastric perforation in a 1-day-old boy is presented. The clinical features are similar to those of meconium peritonitis. Coincidentally, the child had an arachnoid cyst at 25 months of age. To the best of the authors knowledge, this case of congenital immature gastric teratoma associated with gastric perforation mimicking meconium peritonitis, is the first description in the English-language literature. PMID:11987111

Park, Woo-Hyun; Choi, Soon-Ok; Kim, Jong-In

2002-05-01

317

Gastric cancer and trastuzumab: first biologic therapy in gastric cancer  

PubMed Central

Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer.

Gunturu, Krishna S.; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.

2013-01-01

318

Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.  

PubMed Central

The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied. Images FIG. 1 FIG. 2 FIG. 3

Nilsson, O.; Wangberg, B.; Johansson, L.; Modlin, I. M.; Ahlman, H.

1992-01-01

319

Acute Gastric Necrosis Due to Gastric Outlet Obstruction Accompanied with Gastric Cancer and Trichophytobezoar  

PubMed Central

Gastric necrosis due to gastric outlet obstruction is a very rare condition, but it might be fatal if missed or if diagnosis is delayed. Our patient was a 73-year-old male complaining of abdominal pain, distension and dyspnea for 1 day. In plain radiography and computed tomography, a markedly distended stomach and decreased enhancement at the gastric wall were noted. He underwent explo-laparotomy, and near-total gastric mucosal necrosis accompanied by sludge from the soaked laver was noted. A total gastrectomy with esophagojejunostomy was performed, and he recovered without sequelae. Final pathologic examination revealed advanced gastric cancer at the antrum with near-total gastric mucosal necrosis.

Lee, Dosang; Sung, Kiyoung

2011-01-01

320

Gastric Electrical Stimulation  

PubMed Central

Executive Summary Objective The objective of this analysis was to assess the effectiveness, safety and cost-effectiveness of gastric electrical stimulation (GES) for the treatment of chronic, symptomatic refractory gastroparesis and morbid obesity. Background Gastroparesis - Epidemiology Gastroparesis (GP) broadly refers to impaired gastric emptying in the absence of obstruction. Clinically, this can range from the incidental detection of delayed gastric emptying in an asymptomatic person to patients with severe nausea, vomiting and malnutrition. Symptoms of GP are nonspecific and may mimic structural disorders such as ulcer disease, partial gastric or small bowel obstruction, gastric cancer, and pancreaticobiliary disorders. Gastroparesis may occur in association with diabetes, gastric surgery (consequence of peptic ulcer surgery and vagotomy) or for unknown reasons (idiopathic gastroparesis). Symptoms include early satiety, nausea, vomiting, abdominal pain and weight loss. The majority of patients with GP are women. The relationship between upper gastrointestinal symptoms and the rate of gastric emptying is considered to be weak. Some patients with markedly delayed gastric emptying are asymptomatic and sometimes, severe symptoms may remit spontaneously. Idiopathic GP may represent the most common form of GP. In one tertiary referral retrospective series, the etiologies in 146 GP patients were 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson’s disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction and 6% miscellaneous causes. The true prevalence of digestive symptoms in patients with diabetes and the relationship of these symptoms to delayed gastric emptying are unknown. Delayed gastric emptying is present in 27% to 58% of patients with type 1 diabetes and 30% with type 2 diabetes. However, highly variable rates of gastric emptying have been reported in type 1 and 2 diabetes, suggesting that development of GP in patients with diabetes is neither universal nor inevitable. In a review of studies examining gastric emptying in patients with diabetes compared to control patients, investigators noted that in many cases the magnitude of the delay in gastric emptying is modest. GP may occur as a complication of a number of different surgical procedures. For example, vagal nerve injury may occur in 4% to 40% of patients who undergo laparoscopic fundoplication1 for gastroesophageal reflux disease. The prevalence of severe, refractory GP is scantily reported in the literature. Using data from a past study, it has been estimated that the prevalence of severe, symptomatic and refractory GP in the United States population is 0.017%. Assuming an Ontario population of 13 million, this would correspond to approximately 2,000 people in Ontario having severe, symptomatic, refractory GP. The incidence of severe refractory GP estimated by the United States Food and Drug Administration (FDA) is approximately 4,000 per year in the United States. This corresponds to about 150 patients in Ontario. Using expert opinion and FDA data, the incidence of severe refractory GP in Ontario is estimated to be about 20 to 150 per year. Treatment for Gastroparesis To date, there have been no long-term studies confirming the beneficial effects of maintaining euglycemia on GP symptoms. However, it has been suggested that consistent findings of physiologic studies in healthy volunteers and diabetes patients provides an argument to strive for near-normal blood glucose levels in affected diabetes patients. Dietary measures (e.g., low fibre, low fat food), prokinetic drugs (e.g., domperidone, metoclopramide and erythromycin) and antiemetic or antinausea drugs (e.g, phenothiazines, diphenhydramine) are generally effective for symptomatic relief in the majority of patients with GP. For patients with chronic, symptomatic GP who are refractory to drug treatment, surgical options may include jejunostomy tube for feeding, gastrotomy tube for stomach decompression and pyloroplasty for gastric emptying. Few small studies

2006-01-01

321

Laparoscopic gastric bypass versus laparoscopic adjustable gastric banding  

Microsoft Academic Search

BackgroundIndications for and results of laparoscopic adjustable gastric banding (LAGB) and laparoscopic gastric bypass (LGB) are still controversial, especially between Europe and the United States. The recent availability of gastric bandings in the United States made it necessary to compare the two techniques.

Laurent Biertho; Rudolf Steffen; Thomas Ricklin; Fritz F Horber; Alfons Pomp; William B Inabnet; Daniel Herron; Michel Gagner

2003-01-01

322

New spiral bacterium in gastric mucosa  

Microsoft Academic Search

A new spiral bacterium, distinct from Campylobacter pylori, was found in the gastric mucosa of six patients with gastrointestinal symptoms. All patients had chronic active type B gastritis and four had oesophagitis. Culture and microscopy for C pylori infection was negative. These unculturable spiral organisms were probably an incidental finding in patients presenting for upper gastrointestinal endoscopy, but it is

C A McNulty; J C Dent; A Curry; J S Uff; G A Ford; M W Gear; S P Wilkinson

1989-01-01

323

Mouse Models of Gastric Cancer  

PubMed Central

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field.

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

324

Abdominal Surface Potentials and Their Relation to Gastric Motility.  

National Technical Information Service (NTIS)

Reports in the American and Soviet literature have discussed the recording of electrical activity from electrodes on the surface of the abdomen (electrogastrogram or EGG) as a means of measuring gastric motility for research and clinical purposes. The com...

J. K. Stevens N. Worrall

1968-01-01

325

Activation of PGE2-secretion from gastric mucosa by a type I phospholipase C is mediated by a direct release of arachidonic acid.  

PubMed

We investigated the effects of an exogenous Type I phospholipase C (PLC) from clostridium perfringens on arachidonic acid release and prostaglandin synthesis from gastric mucosa by determining PGE2 release from organ cultured rabbit mucosal biopsies as well as PGE2 synthesis and substrate-dependent inactivation of the prostaglandin cyclooxygenase from endogenously released arachidonic acid in mucosal homogenate. PLC dose dependently stimulated PGE2 secretion from organ cultured mucosa to 145% and 245% at 0.1 and 1.0 U/ml during a 60 minute culture period. This effect was not affected by the calmodulin antagonist N-(6-aminohexyl)-1-5-chloro-1-naphthalene-sulfonamide (W-7) or the intracellular calcium chelator 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). PLC could not be substituted by phorbol-12-myristate 13-acetate (PMA), an analogue of the diacylglycerol second messenger functions. During a 15 minute preincubation of mucosal homogenate at 37 degrees C, 1mM CaCl2 stimulated PGE2 synthesis from endogenous arachidonic acid about 5-fold compared to an EDTA-control. In contrast, the residual prostaglandin synthesizing capacity, determined by incubation with excess 14C-labelled arachidonic acid, was reduced by CaCl2 to 37% of the EDTA-value. Quinacrine, an inhibitor of arachidonic acid release from phosphatidylethanolamine, reduced both the stimulation of PGE2 synthesis and the inactivation of prostaglandin cyclooxygenase. Therefore we conclude, that this Ca(2+)-effect reflects activation of the Ca-dependent phospholipase A2 (PLA2) and, as a consequence, substrate-induced inactivation of the prostaglandin cyclooxygenase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1304434

Preclik, G; Stange, E F; Ditschuneit, H

1992-01-01

326

GASTRIC MOTOR DISTURBANCES IN PATIENTS WITH IDIOPATHIC RAPID GASTRIC EMPTYING  

PubMed Central

Background and Aims The mechanisms of “idiopathic” rapid gastric emptying, which is associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. Methods Fasting and postprandial (300kCal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; 7 had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. Results While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (p = 0.002) body mass index (BMI) than normal gastric emptying. MRI visualized propagating contractions at ~ 3 cpm in healthy people and patients. Compared to controls (0.16 ± 0.02, Mean ± SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2–14.0) in patients with rapid (0.24 ± 0.03) but not normal gastric emptying (0.10 ± 0.03). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. Conclusions MRI provides a noninvasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia.

Bharucha, Adil E.; Manduca, Armando; Lake, David S.; Fidler, Jeff; Edwards, Phillip; Grimm, Roger C.; Zinsmeister, Alan R.; Riederer, Stephen J.

2011-01-01

327

Molecular biology of gastric cancer  

Microsoft Academic Search

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic

Eiichi Tahara

1995-01-01

328

Evaluation of gastro protective activity of Fish Oil (Omega 3 Fatty Acids) against experimentally induced acute gastric ulceration in Rats  

Microsoft Academic Search

Fish oils contain the omega-3-fatty acids eicosapentaenoic acid and docosahexaenoic acid precursors of certain eicosanoids that are known to have a wide range of clinical use. The present study was conducted to evaluate the anti ulcer activity of fish oil in HCl-ethanol induced acute ulcer model. The animals were divided into five groups with six rats in each group. Ranitidine

Divakar. V; Sylvia Shanthakumar; Sarath Babu; Karpaga Vinayaga; Raja Muthiah

2012-01-01

329

Gastric emptying following vagotomy and antrectomy and proximal gastric vagotomy.  

PubMed Central

Gastric emptying of solid meals labelled with 129Cs was studied in patients for up to one year after vagotomy and antrectomy or after proximal gastric vagotomy. Significant delay was found one month after vagotomy and antrectomy but this had returned to normal by six months. No delay was found after proximal gastric vagotomy. The effect of posture on gastric emptying was also studied in the same subjects. No significant differences were found between gastric emptying in the supine or sitting positions after solid meals.

Kalbasi, H; Hudson, F R; Herring, A; Moss, S; Glass, H I; Spencer, J

1975-01-01

330

Chronic gastric anisakiasis provoking a bleeding gastric ulcer  

PubMed Central

Gastric anisakiasis is a parasitic disease caused by the gastric mucosal penetration of the Anisakis larvae ingested with raw fish. Acute gastric anisakiasis is diagnosed by the endoscopic visualization of Anisakis larvae along with mucosal edema, erythema, hemorrhage, and/or an ulcer, whereas chronic anisakiasis is often observed as a localized tumor commonly occurring in the submucosal layer, and is characterized by eosinophilic granuloma with edema and embedded Anisakis larvae on pathological examination of surgical specimens. We report here a case of chronic gastric anisakiasis provoking a bleeding gastric ulcer, which is a rare clinical manifestation of this condition.

Kang, Dong Baek; Park, Won Cheol

2014-01-01

331

Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.  

PubMed

The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity. PMID:20645773

Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuro?lu, Mehmet Emin

2010-07-01

332

Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors  

PubMed Central

We evaluated the effects of two laboratory stressors (speech preparation and isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and the extent to which autonomic responses to these stressors and somatization predict reports of motion sickness during exposure to a rotating optokinetic drum. Both stressors prompted a decrease in preejection period (PEP) and respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced decreases in RSA and higher somatization scores predicted increased reports of motion sickness during drum rotation. These results demonstrate that laboratory stressors concurrently affect gastric myoelectrical activity and autonomic control of the heart, and that stressor-induced decreases in RSA and higher levels of somatization predict motion sickness susceptibility.

GIANAROS, PETER J.; QUIGLEY, KAREN S.; MORDKOFF, J. TOBY; STERN, ROBERT M.

2010-01-01

333

Managing Gastric Linitis Plastica  

PubMed Central

Gastric linitis plastica is a diffuse type of cancer which is characterised by a thickening and rigidity of the stomach wall. It is notorious for its failure to cause early symptoms, and patients with symptoms generally have a more advanced form of the disease. We report our 18-month-long experience of managing gastric linitis plastica at Barnsley District General Hospital, UK. In our series of 8 patients, only one patient was offered surgery; the rest were offered palliative or supportive treatment. The findings in our series were consistent with the available evidence that curative treatment is not an option for the majority of cases with linitis plastica.

Jafferbhoy, Sadaf; Shiwani, Hanif; Rustum, Quatullah

2013-01-01

334

Extraction of gastric slow waves from electrogastrograms: combining independent component analysis and adaptive signal enhancement.  

PubMed

The electrogastrogram (EGG), a cutaneous measurement of gastric electrical activity, is a mixture of gastric slow waves and noise. To detect the propagation of gastric slow waves, it is desired to obtain gastric slow waves in each of multichannel EGGs. Recently, independent component analysis (ICA) has shown its efficiency in separating the gastric slow wave from noisy multichannel EGGs. However, this method is not able to recover gastric slow waves in each of the multichannel EGGs. In this paper, a two-stage combined method was proposed for extracting gastric slow waves. First, ICA was performed to separate the gastric slow wave component from noisy multichannel EGGs. Second, adaptive signal enhancement with a reference input derived by the ICA in the first stage was employed to extract gastric slow waves in each channel. Quantitative analysis showed that, with the proposed method, the maximum root-mean-square error between the estimated time lag and its theoretical value in the simulations was only 0.65. The results from real EGG data demonstrated that the combined method was able to extract gastric slow waves from individual channels of EGGs which are important to identify the slow wave propagation. Therefore, the proposed method can be used to detect propagation of gastric slow waves from multichannel EGGs. PMID:15865135

Liang, H

2005-03-01

335

Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells  

SciTech Connect

Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M-BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.

Yasuda, Hiroshi [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan)]. E-mail: hiroshi-yasuda@showa-university-fujigaoka.gr.jp; Hirata, Shuko [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan); Inoue, Kazuaki [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan); Mashima, Hirosato [Department of Gastroenterology, University of Tokyo, Tokyo (Japan); Ohnishi, Hirohide [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Yoshiba, Makoto [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan)

2007-03-02

336

Mouse Models of Gastric Carcinogenesis  

PubMed Central

Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

Yu, Sungsook; Yang, Mijeong

2014-01-01

337

beta-Glucoronidase and the gastric epithelial cell. A study using organ culture.  

PubMed

In an attempt to determine the significance of increased beta-glucuronidase content of gastric juice of patients with gastric carcinoma, gastric mucosal cells were exposed, in organ culture technique, to a known gastric carcinogen and indices of carcinogenic activity were studied in the ambient fluid and in the mucosal cells. Isotopic methods were used to determine cell viability. Indices of carcinogenic activity in the ambient fluid were beta-glucuronidase and lactate production and changes in the LDH isoenzyme pattern of the homogenates of the exposed cells were also studied. Incubation with the carcinogen resulted in increased production of beta-glucuronidase and lactate, suggesting the increased beta-glucuronidase activity in the gastric juice of patients with gastric cancer indicates malignancy. PMID:615735

Tayler, R; Orwell, R L; Piper, D W

1977-01-01

338

Usefulness of Indocyanine Green Angiography for Evaluation of Blood Supply in a Reconstructed Gastric Tube During Esophagectomy  

PubMed Central

We report a case of necrosis of a reconstructed gastric tube in a 77-year-old male patient who had undergone esophagectomy. At the time of admission, the patient had active gastric ulcers, but these were resolved by treatment with a proton pump inhibitor. Subtotal esophagectomy with gastric tube reconstruction was performed. Visually, the reconstructed gastric tube appeared to be well perfused with blood. Using indocyanine green (ICG) fluorescence imaging the gastroepiploic vessels were well enhanced and no enhancement was visable 3 to 4 cm from the tip of the gastric tube. Four days after esophagectomy, gastric tube necrosis was confirmed, necessitating a second operation. The necrosis of the gastric tube matched the area that had been shown to lack blood perfusion by ICG angiography imaging. It seems that ICG angiography is useful for the evaluation of perfusion in a reconstructed gastric tube.

Ishiguro, Toru; Kumagai, Youichi; Ono, Tomojiro; Imaizumi, Hideko; Honjo, Hiroaki; Suzuki, Okihide; Ito, Tetsuya; Haga, Norihiro; Kuwabara, Kohki; Sobajima, Jun; Kumamoto, Kensuke; Ishibashi, Keiichoro; Baba, Hiroyuki; Ishida, Hideyuki; Kawano, Tatsuyuki

2012-01-01

339

Gastric cancer: overview.  

PubMed

This review provides a state of the art description of gastric cancer etiology, the infectious agent, host factors, the precancerous cascade, clinical aspects, and prevention strategies. The biology of Helicobacter pylori, the primary causative agent, is discussed as well as the environmental factors that may modulate its effects. PMID:23639637

Correa, Pelayo

2013-06-01

340

Gastric Motility: The Electrogastrogram.  

National Technical Information Service (NTIS)

A method is described for recording gastric motility, the EGG, in the intact organism. The method is based upon detection of the substantial potentials generated by the stomach through electrodes placed on the skin of the abdomen. Methods for analyzing th...

R. W. Russell R. M. Stern

1967-01-01

341

Brain regulation of gastric secretion: influence of neuropeptides.  

PubMed Central

Several neuropeptides injected intracisternally were assessed for their effects on gastric secretion in rats. Bombesin (1 microgram) completely suppressed gastric acid secretion, produced the volume of gastric secretion, and partially blocked insulin- or 2-deoxy-D-glucose-induced stimulation of gastric acid output. The inhibitory effect of this peptide is dose-dependent, long-acting, reversible, and specific. Bombesin response appears to be central nervous system-mediated; its expression is not dependent on the vagus nerve or the adrenal glands, and does not rely on a decrease in gastrin secretion. Among seven other peptides tested, only beta-endorphin and a potent gonadotropin releasing-factor (gonadoliberin) agonist significantly reduced gastric acid secretion, with an activity ca. 100 times less than that of bombesin. The presence of bombesin-like material in rat brain and the high potency of bombesin to inhibit gastric secretion suggest that this peptide may be of physiologic significance as a chemical messenger involved in brain modulation of gastric secretion.

Tache, Y; Vale, W; Rivier, J; Brown, M

1980-01-01

342

Blunted Peripheral and Central Responses to Gastric Mechanical and Electrical Stimulations in Diet-induced Obese Rats  

PubMed Central

Background/Aims The increase in the prevalence of obesity is attributed to increased food intake and decreased physical activity in addition to genetic factors. Altered gut functions have been reported in obese subjects, whereas, little is known on the possible alterations in brain-gut interactions in obesity. The aim of the study was to explore possible alterations in gastric myoelectrical activity, gastric emptying, autonomic functions and central neuronal responses to gastric stimulations in diet-induced obese rats. Methods Gastric myoelectrical activity, gastric emptying and heart rate variability were recorded in lean and obese rats; extracellular neuronal activity in the ventromedial hypothalamus and its responses to gastric stimulations were also assessed. Results (1) Gastric emptying was significantly accelerated but gastric myoelectrical activity was not altered in obese rats; (2) the normal autonomic responses to feeding were absent in obese rats, suggesting an impairment of postprandial modulation of autonomic functions; and (3) central neuronal responses to gastric stimulations (both balloon distention and electrical stimulation) were blunted in obese rats, suggesting impairment in the brain-gut interaction. Conclusions In diet-induced obese rats, gastric emptying is accelerated, postprandial modulations of autonomic functions is altered and central neuronal responses to gastric stimulations are attenuated. These alterations in peripheral, autonomic and brain-gut interactions may help better understand pathogenesis of obesity and develop novel therapeutic approaches for obesity.

Zhang, Jing; Sha, Weihong; Zhu, Hongbing

2013-01-01

343

The role of sensory C-fibers in response of vagal afferent stimulation by gastric distension in rats with experimental chronic gastric ulcer.  

PubMed

There is growing evidence that gastric vagal afferent input may contribute to the altered sensations associated with gastrointestinal disorders. The aim of our study was to evaluate gastric vagal afferents (VA) activity in rats with experimental gastric ulcer and ulcer healing. The study was carried out on rats with gastric ulcer (GU), including, a group with perivagal capsaicin pretreatment (CAP), a group with capsaicin administration in gastric ulcer (CAP+GU) animals and control rats. In all rats electrical VA activity was recorded and analysed. In GU rats recordings were carried out in chronic ulcer and ulcer healing. In GU and CAP+GU groups gastric balloon distensions with vagal recording was performed on 3(rd) day after ulcer induction. Usually, experimental GU healed spontaneously within 2 weeks. Three days after acetic acid application when GU fully develop, the frequency of the basal VA activity was almost 3-times higher than in the control intact rats and remained elevayed until 4(th) week after ulcer induction. VA response to gastric distension increased concomitantly with increased balloon volume in both GU and control animals, but it was several times higher in GU rats. Perivagal capsaicin application decreased the frequency of spontaneous VA activity and decreased the response of VA to gastric distension. In CAP+GU, spontaneous activity as well as the response to gastric distension were higher than in CAP rats. Our study shows that GU induced inflammatory changes increase sensitivity of gastric VA. Capsaicin-sensitive vagal afferent fibers may play some role in this phenomenon. Peripheral sensitization of VA persists even when gastric ulcer is completely healed. PMID:18812637

Zurowski, D; Dobrek, ?; Bugajski, A; Thor, P J

2008-08-01

344

Transcatheter arterial embolization in gastric cancer patients with acute bleeding  

Microsoft Academic Search

The safety and clinical effectiveness of transcatheter arterial embolization for bleeding associated with unresectable gastric\\u000a cancer was evaluated. Twenty-three patients with bleeding from unresectable gastric cancer underwent transcatheter arterial\\u000a embolization. Of the 23 patients, eight showed signs of active bleeding, such as contrast extravasation or pseudoaneurysm,\\u000a seven showed only tumor staining, and the remaining eight patients showed negative angiographic findings.

Hyun Joo Lee; Ji Hoon Shin; Hyun-Ki Yoon; Gi-Young Ko; Dong-Il Gwon; Ho-Young Song; Kyu-Bo Sung

2009-01-01

345

Genetic alterations of the CHOP gene in gastric cancers  

Microsoft Academic Search

CHOP, a member of the C\\/EBP family of the transcriptional factor, showed a tumor suppressor activity by binding to TCF and\\u000a inhibiting the Wnt signaling pathway. In this study, to determine whether genetic alterations of CHOP gene are involved in the development and\\/or progression of the gastric cancers, we have screened a set of 47 gastric adenoma\\u000a and 81 sporadic

Jae Hwi Song; Jong Kyung Park; Jeong Whan Yoon; Suk Woo Nam; Jung Young Lee; Won Sang Park

2011-01-01

346

Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c-myc  

Microsoft Academic Search

Apoptosis plays a major role in gastrointestinal epithelial cell turnover, ulcerogenesis and tumorigenesis. We have examined apoptosis induction by non-steroidal anti-inflammatory drugs (NSAIDs) in human gastric (AGS) cancer cells and the role of protein kinase C (PKC) and apoptosis-related oncogenes. After treatment with aspirin or indomethacin, cell growth was quantified by MTT assay, and apoptosis was determined by acridine orange

G H Zhu; B C Y Wong; M C Eggo; C K Ching; S T Yuen; E Y T Chan; K C Lai; S K Lam; BCY Wong

1999-01-01

347

Bactericidal activities of the cationic steroid CSA13 and the cathelicidin peptide LL37 against Helicobacter pylori in simulated gastric juice  

Microsoft Academic Search

Background  The worldwide appearance of drug-resistant strains of H. pylori motivates a search for new agents with therapeutic potential against this family of bacteria that colonizes the stomach,\\u000a and is associated with adenocarcinoma development. This study was designed to assess in vitro the anti-H. pylori potential of cathelicidin LL-37 peptide, which is naturally present in gastric juice, its optimized synthetic analog

Katarzyna Leszczy?ska; Andrzej Namiot; David E Fein; Qi Wen; Zbigniew Namiot; Paul B Savage; Scott Diamond; Paul A Janmey; Robert Bucki

2009-01-01

348

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole  

PubMed Central

Background Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Methods Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. Results 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p?=?0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p?gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. Trial registration ClinicalTrial.gov: NCT01136317

2014-01-01

349

Specific food structures supress appetite through reduced gastric emptying rate  

PubMed Central

The aim of this study was to determine the extent to which gastric layering and retention of a meal could be used to reduce appetite using the same caloric load. Liquid (control) and semi-solid (active) meals were produced with the same protein, fat, carbohydrate, and mass. These were fed to 10 volunteers on separate days in a crossover study, and subjective appetite ratings, gastric contents, and plasma cholecystokinin (CCK) were assessed over a period of 3 h. The active meal showed food boluses in the stomach persisting for ?45 min, slower emptying rates, and lower plasma CCK levels over the first hour. After the first hour, both gastric emptying rates and plasma CCK levels were similar for both systems and slightly increased compared with the unfed situation. Despite the lower plasma CCK levels for the active meal over the first hour, this meal reduced appetite more than the control meal over the 3 h of the study. For a moderately increased plasma CCK level in the fed state, appetite was correlated with the volume of gastric contents rather than gastric emptying rates or plasma CCK. This suggests that enhanced gastric retention was the key factor in decreasing appetite and was probably mediated by a combination of intestinal nutrient sensing and increased viscosity in the stomach.

Rafiee, Hameed; Malcolm, Paul; Salt, Louise; van Aken, George

2013-01-01

350

Guanosine negatively modulates the gastric motor function in mouse.  

PubMed

The aim of the present study was to evaluate if guanine-based purines may affect the gastric motor function in mouse. Thus, the influence of guanosine on the gastric emptying rate in vivo was determined and its effects on spontaneous gastric mechanical activity, detected as changes of the intraluminal pressure, were analyzed in vitro before and after different treatments. Gastric gavage of guanosine (1.75-10 mg/kg) delayed the gastric emptying. Guanosine (30 ?M-1 mM) induced a concentration-dependent relaxation of isolated stomach, which was not affected by the inhibition of the purine nucleoside phosphorylase enzyme by 4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-H. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine, a membrane nucleoside transporter inhibitor, but not affected by 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine, a nonselective adenosine receptor antagonist, or by tetrodotoxin, a blocker of neuronal voltage-dependent Na(+) channels. Moreover, guanosine-induced effects persisted in the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase or tetraethylammonium, a nonselective potassium channel blocker, but they were progressively reduced by increasing concentrations of 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor. Lastly, the levels of cyclic adenosine monophosphate (cAMP), measured by ELISA, in gastric full thickness preparations were increased by guanosine. In conclusion, our data indicate that, in mouse, guanosine is able to modulate negatively the gastric motor function, reducing gastric emptying and inducing muscular relaxation. The latter is dependent by its cellular uptake and involves adenylyl cyclase activation and increase in cAMP intracellular levels, while it is independent on neural action potentials, adenosine receptors, and K(+) channel activation. PMID:23839776

Zizzo, Maria Grazia; Mulè, Flavia; Amato, Antonella; Maiorana, Francesca; Mudò, Giuseppa; Belluardo, Natale; Serio, Rosa

2013-12-01

351

Antisecretory Drugs for Diarrheal Disease  

Microsoft Academic Search

Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2–3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory

Michael J. G. Farthing

2006-01-01

352

Gastric cancer risk after vagotomy.  

PubMed Central

The risk of gastric cancer after vagotomy for benign gastric and duodenal disease was examined in a population based cohort of 7198 patients operated on during 1971-79 and followed up until 1988. After exclusion of the first year of follow up there were 34 cases of gastric cancer compared with 25.6 expected (standardised incidence ratio (SIR) = 1.33; 95% confidence intervals (CI) 0.92 to 1.86). Separate analyses by duration of follow up, sex, age at operation, underlying diagnosis, and operative procedures did not show any significant increased or decreased risk of gastric cancer in any of the subgroups. In conclusion, decreased gastric acid secretion after vagotomy does not increase the risk of gastric cancer in the first 10 years after operation or in the subgroup followed up for 10-18 years. A longer follow-up is needed before an excess risk can be excluded.

Lundegardh, G; Ekbom, A; McLaughlin, J K; Nyren, O

1994-01-01

353

Evidence for the essential role of Helicobacter pylori in gastric ulcer disease  

Microsoft Academic Search

Helicobacter pylori (H pylori) eradication heals chronic active type B gastritis and dramatically changes the natural history of duodenal ulcer disease. There are few data concerning the role of anti-H pylori treatment in gastric ulcer disease. A total of 83 patients presenting with H pylori positive active gastric ulcer disease were treated with omeprazole and antibiotics (amoxicillin, ciprofloxacin, roxithromycin) in

J Labenz; G Börsch

1994-01-01

354

Role of neutrophil elastase in stress-induced gastric mucosal injury in rats  

Microsoft Academic Search

Activated neutrophils play an important role in tissue injury by releasing various inflammatory mediators capable of damaging endothelial cells. To investigate whether neutrophil elastase (NE) is involved in stress-induced gastric mucosal injury, we examined the effects of 2 NE inhibitors (ONO-5046 and L-658 758) as well as nitrogen mustard-induced leukocytopenia on the formation of gastric mucosal lesions, gastric mucosal blood

Wenge Liu; Kenji Okajima; Kazunori Murakami; Naoaki Harada; Hirotaka Isobe; Tetsumi Irie

1998-01-01

355

Recent Advances in the Physiology of Gastric Acid Secretion  

PubMed Central

The classic scheme of gastric acid secretion which divided the digestive period into cephalic, gastric and antral phases has become obsolete in the last 10 years. These “phases” are now seen as concurrently acting mechanisms which depend upon one another to be fully efficient. About half of all gastrin released during a meal is dependent upon vagal stimulation of the antrum. Also, vagotomy desensitizes the acid-secreting parietal cells to the effect of all other types of stimuli. The number of parietal cells (parietal cell mass) varies greatly according to the gastric secretory activity of each individual. It is highest with duodenal ulcer and lowest with gastric ulcer. Parietal cell hyperplasia or atrophy can be induced experimentally, but the factors controlling the size of the parietal cell mass in man have not been studied. A scheme of acid secretion which incorporates recent advances is presented. ImagesFig. 1

Perey, Bernard J. F.

1963-01-01

356

Roles of gastric GATA DNA-binding proteins.  

PubMed

The gastric H+/K(+)-ATPase is a P-type ATPase that is specifically expressed in gastric parietal cells and is responsible for acid secretion into the stomach. We have found one or more gastric mucosal nuclear proteins that recognize a sequence motif in the 5'-upstream regions of the H+/K(+)-ATPase alpha- and beta-subunit genes. This gastric motif, (G/C)PuPu(G/C)NGAT(A/T)PuPy, may be a binding site for a positive transcriptional regulator that functions specifically in parietal cells. We further demonstrated using cDNA cloning and in situ hybridization that novel zinc-finger proteins (GATA-GT1 and GATA-GT2) are present in the gastric parietal cells and bind to this motif. The proteins activate the transcription of the reporter gene with the 5'-upstream region of the H+/K(+)-ATPase beta-subunit gene. These results suggest that gastric GATA DNA-binding proteins have important roles in transcriptional activation of H+/K(+)-ATPase genes in the parietal cells. PMID:8867276

Maeda, M; Kubo, K; Nishi, T; Futai, M

1996-03-01

357

Laparoscopic Adjustable Gastric Banding  

Microsoft Academic Search

. We introduced open adjustable silicone gastric banding (ASGB) for treatment of morbid obesity in our institution\\u000a in 1991. It was done in a prospective study comparing ASGB with vertical banded gastroplasty (VBG) with regard to weight loss.\\u000a After 200 cases of open ASGB and 210 VBG procedures and the encouraging weight loss results, we started laparoscopic placement\\u000a of the

Mitiku Belachew; Marc Legrand; Vernon Vincent; Michel Lismonde; Nicole Le Docte; Veronique Deschamps

1998-01-01

358

Interleukin-6 Mediates Epithelial-Stromal Interactions and Promotes Gastric Tumorigenesis  

PubMed Central

Interleukin-6 (IL-6) is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial–stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6–positive cells in the stroma showed positive staining for the fibroblast marker ?-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6?/?) mice with wild-type (WT) mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6?/? mice, compared with WT mice. Impaired tumor development in IL-6?/? mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3–related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell–conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1) receptor antagonist and siRNA inhibition of IL-1? in the fibroblasts. IL-1? mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1? in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.

Kinoshita, Hiroto; Hirata, Yoshihiro; Nakagawa, Hayato; Sakamoto, Kei; Hayakawa, Yoku; Takahashi, Ryota; Nakata, Wachiko; Sakitani, Kosuke; Serizawa, Takako; Hikiba, Yohko; Akanuma, Masao; Shibata, Wataru; Maeda, Shin; Koike, Kazuhiko

2013-01-01

359

Effects of Opuntia ficus-indica var. Saboten stem on gastric damages in rats.  

PubMed

The effects of the dried stem powder of Opuntia ficus-indica var. saboten (OF-s) were investigated on gastric lesion and ulcer models in rats. It showed significant inhibition in HCl ethanol-induced gastric lesion at the doses of 200 and 600 mg/kg p.o. and in HCl.aspirin-induced gastric lesion at 600 mg/kg p.o. OF-s also showed significant inhibition in indomethacin-induced gastric lesion at the doses of 200 and 600 mg/kg, p.o. However, it did not affect both the aspirin-induced and Shay ulcers in rats. It also did not affect gastric juice secretion, acid output and pH. These data indicate that OF-s only possesses pronounced inhibitory action on gastric lesion without antiulcer activity in rats. PMID:11885695

Lee, Eun Bang; Hyun, Jin Ee; Li, Da Wei; Moon, Yung In

2002-02-01

360

Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a rat model.  

PubMed

Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a stimulator of gastric vagal afferent nerves. The aim of the present study was to examine the possibility that l-Glu supplementation of a protein-rich liquid diet may prevent the incidence of diarrhoea during repetitive intra-gastric tube feeding. The gastric vagal afferent nerve recording of rats indicated that intra-gastric administration of a protein-rich liquid diet supplemented with 0·5 % monosodium glutamate enhanced the basal afferent activities seen with the protein-rich diet alone. The examination of the faeces showed that the addition of monosodium glutamate to the liquid diet significantly prevented the incidence of diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra-gastric tube feeding by sending visceral glutamate information from the stomach to the brain. PMID:21733333

Somekawa, Shinji; Hayashi, Naoki; Niijima, Akira; Uneyama, Hisayuki; Torii, Kunio

2012-01-01

361

Gastric cancer after laparoscopic adjustable gastric banding: case report  

PubMed Central

Gastric cancer in patients who have undergone bariatric surgery is rare. The authors present a case of stomach cancer in a patient 6 years after adjustable silicone gastric band placement. The tumour was located below the band, not in its direct vicinity. Aetiological and risk factors of stomach cancer incidence in obese patients are discussed in this case study.

Janczak, Przemyslaw; Modzelewski, Bogdan

2012-01-01

362

Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats.  

PubMed

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes. PMID:23965296

Xu, Luo; Qu, Zhuling; Guo, Feifei; Pang, Mingjie; Gao, Shengli; Zhu, Hai; Gu, Fang; Sun, Xiangrong

2013-10-01

363

Pharmacological evidence for the participation of NO-cGMP-KATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat.  

PubMed

Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whether these increased NO levels are associated with activation of intracellular signaling pathways. Thus, the purpose of this study was to investigate the role of NO-cGMP-KATP pathway in the gastric protective effect of curcumin during indomethacin-induced gastric injury in the rat. Adult female Wistar rats were gavaged with curcumin (3-300mg/kg, p.o.) or omeprazole (30mg/kg, p.o.) 30min before indomethacin insult (30mg/kg, p.o.). Other groups of rats were administered L-NAME (70mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1mg/kg, i.p.; blocker of ATP-sensitive potassium (KATP) channels) 30min before curcumin (30mg/kg, p.o.). 3h after indomethacin administration, rats were sacrificed and gastric injury was evaluated by determining total damaged area. A sample of gastric tissue was harvested and processed to quantify organic nitrite levels. Curcumin significantly protected against indomethacin-induced gastric injury and this effect was comparable to gastroprotective effect by omeprazole. L-NAME, ODQ and glibenclamide significantly prevented the curcumin-mediated gastric protective effect in the indomethacin-induced gastric injury model. Furthermore, curcumin administration induced a significant increase in gastric nitric oxide levels as compared to vehicle administration. Our results show for the first time that curcumin activates NO/cGMP/KATP pathway during its gastro protective action. PMID:24607410

Díaz-Triste, Nadia Estela; González-García, Martha Patricia; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

2014-05-01

364

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer  

PubMed Central

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-?-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of ?-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the ?-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of