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1

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

2

Gastric antisecretory and antiulcer effects of WHR1582A, a compound exerting alpha-2 adrenoceptor agonist activity.  

PubMed

The gastric antisecretory and antiulcer effects of a novel compound, [1-(2,-dimethylphenyl)-3-isobutoxyamidinourea]hydrochloride (WHR1582A), are described. WHR1582A was active in preclinical ulcer models induced by 18-hr pylorus ligation, aspirin, indomethacin, reserpine, stress or cysteamine. WHR1582A inhibited acid secretion in the pylorus-ligated rat and in the anesthetized, lumen-perfused rat. The antisecretory effects of WHR1582A were antagonized by yohimbine, RX781094A and phentolamine. Propranolol, prazosin, corynanthine, methysergide, sulpiride and pimozide were unable to block its activity. WHR1582A blocked acid secretion stimulated by 2-deoxy-D-glucose but was inactive against the direct parietal cell stimulants carbachol and dimaprit. WHR1582A also inhibited electrically stimulated contractions that were mediated via the vagus in the isolated rat stomach preparation. The antisecretory activity of WHR1582A was not due to a reduction in gastric mucosal blood flow. These results demonstrate that WHR1582A is an effective antiulcer-antisecretory agent that exerts its gastric effects through the activation of alpha-2 adrenoceptors located presynapitcally on the vagus. PMID:2883297

DiJoseph, J F; Eash, J R; Mir, G N

1987-04-01

3

Gastric Transmucosal Potential Difference: Effect of Antisecretory and Gastroprotective Drugs  

Microsoft Academic Search

1.Ion transport and electrical resistance of the gastric mucosa are responsible for the generation of the transmucosal potential difference (PD), which is considered an index of mucosal integrity.2.The aim of the present work was to study the effect of some antisecretory and gastroprotective agents on PD in stomachs damaged by ethanol.3.Control PD values measured in anesthetized rats were 35 to

Viera Nosál'ová; Anna Babul'ová; Viktor Bauer

1998-01-01

4

Gastric antisecretory effects of synthetic cannabinoids after central or peripheral administration in the rat.  

PubMed

Previous studies have revealed that cannabinoid (CB)-receptor agonists inhibit gastric acid secretion stimulated by indirectly acting agents, but not by histamine. Aiming to investigate whether central or peripheral mechanisms are involved, the effects of the synthetic CB-receptor agonists WIN55,212-2 and HU-210, administered either intracerebroventricularly (i.c.v.) or intravenously (i.v.) to the anaesthetized rat with lumen-perfused stomach, against gastric acid secretion induced by pentagastrin were tested. Injected i.c.v., both WIN55,212-2 (50 and 100 microg/kg) and HU-210 (25, 50 and 100 microg/kg) were ineffective on either basal secretion or acid output induced by pentagastrin (7.7 microg/kg, i.v.). By contrast, i.v. injections of WIN55,212-2 (100 and 1000 microg/kg) or HU-210 (10-100 microg/kg) significantly inhibited pentagastrin-induced acid secretion, maximal reductions being 75.70 and 82.24% for WIN55,212-2 and HU-210, respectively. The gastric antisecretory effect of HU-210 was prevented by administration of the selective CB(1)-receptor antagonist SR141716A (1000 microg/kg, i.v.). These results show that CB(1)-receptors mediating inhibition of gastric acid secretion in the rat are mainly peripherally located. PMID:15561471

Adami, Maristella; Zamfirova, Rossitsa; Sotirov, Emil; Tashev, Roman; Dobrinova, Yordanka; Todorov, Simeon; Coruzzi, Gabriella

2004-12-15

5

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

2009-12-03

6

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats.  

PubMed

In the present investigation, an ethanol extract of celery [Apium graveolens L. (Apiaceae/Umbelliferae)], at doses of 250 and 500 mg/kg body weight, was evaluated for antigastric ulcer activity using various experimental gastric ulcer models in rats. Ulcers were induced by indomethacin, cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) and cold restraint stress. Gastric secretory studies were undertaken by using pylorus ligation (Shay rat model). In addition to gastric wall mucus (GWM), non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in gastric tissues after 80% ethanol treatment. Pretreatment of celery extract produced dose-dependent reduction in all experimentally induced gastric lesions. Ethanol (80%) decreased the levels of GWM, NP-SH and increase in MDA concentration in gastric tissue. Celery extract showed the ability to significantly replenish the ethanol-induced depleted levels of GWM and gastric mucosal NP-SH. The gastric mucosal MDA level was also significantly lowered in extract pretreated rats. The celery extract showed stomach protection against the models used for ulcerogenesis. Results were further confirmed by using histopathological assessment. The phytochemical screening showed the presence of various chemical constituents such as flavonoids, tannins, volatile oils, alkaloids, sterols and/or triterpenes. Acute toxicity test revealed no deleterious or toxic symptoms or mortality over a period of 14 days. However, the LD(50) was found to be 7.55 g/kg, and showed a large margin of safety. The results suggest that Apium graveolens extract significantly protects the gastric mucosa and suppresses the basal gastric secretion in rats, possibly through its antioxidant potential. PMID:20645778

Al-Howiriny, Tawfeq; Alsheikh, Abdulmalik; Alqasoumi, Saleh; Al-Yahya, Mohammed; ElTahir, Kamal; Rafatullah, Syed

2010-07-01

7

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

8

Development of monoclonal antibodies for detection of Antisecretory Factor activity in human plasma  

Microsoft Academic Search

Antisecretory Factor (AF) is expressed in most tissues and can be demonstrated in plasma and other body fluids. Most of the AF in plasma is in an inactive form and activation of AF occurs after exposure to bacterial toxins or after intake of various dietary components. Patients with chronic diseases involving disturbances in inflammatory and secretory processes may benefit from

Ewa Johansson; Ivar Lönnroth; Ingela Jonson; Stefan Lange; Eva Jennische

2009-01-01

9

Antisecretory activity of plants used to treat gastrointestinal disorders in Mexico  

Microsoft Academic Search

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 300mg\\/kg. From 56 samples tested, both extracts from Chiranthodendron pentadactylon, Hippocratea excelsa and Ocimum basilicum were the most potent with inhibition

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

2006-01-01

10

Gastric antisecretory effects of synthetic cannabinoids after central or peripheral administration in the rat  

Microsoft Academic Search

Previous studies have revealed that cannabinoid (CB)-receptor agonists inhibit gastric acid secretion stimulated by indirectly acting agents, but not by histamine. Aiming to investigate whether central or peripheral mechanisms are involved, the effects of the synthetic CB-receptor agonists WIN55,212-2 and HU-210, administered either intracerebroventricularly (i.c.v.) or intravenously (i.v.) to the anaesthetized rat with lumen-perfused stomach, against gastric acid secretion induced

Maristella Adami; Rossitsa Zamfirova; Emil Sotirov; Roman Tashev; Yordanka Dobrinova; Simeon Todorov; Gabriella Coruzzi

2004-01-01

11

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

2013-07-20

12

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

2013-02-23

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

2005-09-19

14

PD136,450: A CCK 2 (gastrin) receptor antagonist with antisecretory, anxiolytic and antiulcer activity  

Microsoft Academic Search

This study investigated the effects of PD-136,450 (PD), a highly selective ligand for the CCK2 receptor, on gastric acid and pancreatic secretions, gastric cytoprotection and anxious behaviour in the rat and rabbit. PD inhibited gastrin (but not dimaprit) stimulated acid secretion in anaesthetized and conscious rats (IC50 of 1 mg kg-1 sc) and inhibited 14C-aminopyrine uptake in isolated gastric glands

S. M. A. Bastaki; M. Y. Hasan; S. I. Chandranath; A. Schmassmann; A. Garner

2003-01-01

15

Action of pentacaine on gastric acid secretion  

Microsoft Academic Search

The action of pentacaine, a new prospective antiulcer drug with gastric cytoprotective activity, on gastric acid secretion was analysed and compared with the action of other antisecretory drugs. The drugs were given orally or intraduodenally to Wistar rats after pylorus ligation. The gastric acid secretion was studied under basal or stimulated (histamine, pentagastrin, carbachol) conditions. Oral administration of pentacaine, oxethazaine

A. BabuTovfi; V. Nosá?ová; V. Bauer; ?. Buran

1988-01-01

16

Verbascoside isolated from Tectona grandis mediates gastric protection in rats via inhibiting proton pump activity.  

PubMed

Evidences have suggested that Tectona grandis (TG) attenuates gastric mucosal injury; however its mechanism has not yet been established. The aim of present study was to evaluate the gastroprotective mechanism of ethanolic extract of TG (E-EtOH), butanolic fraction (Fr-Bu) and to identify its active constituents. Anti-ulcer activities were evaluated against cold restraint (CRU) and pyloric ligation (PL) induced gastric ulcer models and further confirmed through H(+) K(+)-ATPase inhibitory activity. Cytoprotective activity was evaluated in alcohol (AL) induced gastric ulcer model and further through PGE(2) level. E-EtOH and Fr-Bu attenuated ulcer formation in CRU. Moreover E-EtOH and Fr-Bu displayed potent anti-secretory activity as evident through reduced free acidity and pepsin activity in PL, confirmed further by in vitro inhibition of H(+) K(+)-ATPase activity. In addition cytoprotective potential of E-EtOH and Fr-Bu were apparent with protection in AL model, increased PGE(2) content and enhanced mucin level in PL. Phytochemical investigations of Fr-Bu yielded terpenoides and a phenolic glycoside, verbascoside. The anti-secretory mechanism of verbascoside mediated apparently through inhibition of H(+) K(+)-ATPase with corresponding decrease in plasma gastrin level, is novel to our finding. Gastroprotection elicited by TG might be through proton pump inhibition and consequent augmentation of the defensive mechanism. PMID:20388534

Singh, Neetu; Shukla, Nivedita; Singh, Pratibha; Sharma, Rolee; Rajendran, S M; Maurya, Rakesh; Palit, Gautam

2010-04-11

17

Evaluation of antiulcer and antisecretory potential of Linum usitatissimum fixed oil and possible mechanism of action.  

PubMed

The aim of the study was to evaluate the antiulcer activity of Linum usitatissimum fixed oil against aspirin-, indomethacin-, ethanol-, reserpine-, serotonin- and stress-induced gastric ulceration in rats and histamine-induced gastric ulceration in guinea pigs. Attempts were also made to evaluate the in vitro anticholinergic and antihistaminic activity and in vivo antisecretary and antiulcer activity of oil following pylorus ligation in rats. L. usitatissimum fixed oil exhibited significant antiulcer activity against different ulcerogens in experimental animal models. The fixed oil significantly inhibited acetylcholine- and histamine-induced contraction of guinea pig and rat ileums, respectively, suggesting its anticholinergic and antihistaminic activity. The oil also exhibited significant inhibitory effect on gastric secretion/total acidity and aspirin-induced gastric ulceration in pylorus-ligated rats. The lipoxygenase inhibitory, histamine antagonistic and antisecretory (anticholinergic) effects of the oil could probably have contributed towards antiulcer activity. L. usitatissimum fixed oil may be considered to be a drug of natural origin which possesses significant antiulcer activity. The present observation is the first experimental data showing antiulcer activity of L. usitatissimum fixed oil. PMID:20405222

Kaithwas, Gaurav; Majumdar, Dipak K

2010-04-20

18

Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine  

Microsoft Academic Search

BACKGROUND: Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg\\/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. METHODS: Adult

Martin E Edelsbrunner; Motoko Nakano; Peter Holzer

2009-01-01

19

Gastric lipase: crystal structure and activity  

Microsoft Academic Search

Fat digestion in humans requires not only the classical pancreatic lipase but also gastric lipase, which is stable and active despite the highly acidic stomach environment. We have solved the structure of recombinant human gastric lipase at 3.0 Ĺ resolution, the first structure to be described within the mammalian acid lipase family. This globular enzyme (379 residues) consists of a

Stéphane Canaan; Alain Roussel; Robert Verger; Christian Cambillau

1999-01-01

20

Prostaglandins and gastric mucosal protection by esaprazole in rats.  

PubMed

Esaprazole, N-cyclohexyl-1-piperazineacetamide monohydrochloride, was studied for its activity to prevent gastric mucosal damage induced by several necrotizing agents in the rat. Its effects on acid gastric secretion and the role of gastric mucosal prostaglandin generation were also investigated. Esaprazole, given orally, dose dependently prevented the formation of mucosal damage induced by absolute ethanol, 0.2 N NaOH or 0.6 N HCl. This activity occurred at doses lower than the antisecretory doses. Esaprazole was also found to increase the gastric mucosal prostaglandin content but at doses that exceeded the cytoprotective doses. The failure of indomethacin to impair the gastric mucosal protection provided by esaprazole suggests that mechanisms other than mobilization of endogenous prostaglandins may be involved. PMID:2272352

Zuccari, G; Clavenna, G; Sala, A; Viganň, T; Crivellari, M T; Folco, G

1990-10-01

21

Activated Neutrophils Impair Gastric Cytoprotection: Role of Neutrophil Elastase  

Microsoft Academic Search

Neutrophil elastase decreases production of PGI2 by cultured endothelial cells. Thus, neutrophil elastase may play an important role in gastric mucosal injury by decreasing the tissue level of PGI2, an important gastric cytoprotective substance. We examined whether activated neutrophils inhibit gastric PGI2 production in rats subjected to water-immersion restraint stress. Gastric 6-keto-PGF1a levels were determined by enzyme immunoassay. Gastric mucosal

Naoaki Harada; Kenji Okajima; Wenge Liu; Mitsuhiro Uchiba

2000-01-01

22

Hydrogen potassium adenosine triphosphatase activity inhibition and downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum burmannii in gastric parietal cells  

PubMed Central

This study assessed the gastric acid antisecretory effect of DLBS2411 fractionated from Cinnamomum burmannii. Hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) activity and its gene expression were observed, and the antioxidant activity of DLBS2411 was also investigated. Treatment of DLBS2411 decreased the level of H+/K+ ATPase messenger RNA expression on human embryonic kidney 293 cells and rat gastric parietal cells in a dose-dependent manner, in vitro and ex vivo. DLBS2411 also acted as a competitive inhibitor by showing inhibition in gastric H+/K+ ATPase activity at various pHs. In gastric ulcer animal models induced with indomethacin and ethanol, DLBS2411showed a reduction in the number of petechiae, suggesting that the fraction also confers gastroprotective activity. Moreover, DLBS2411 was also found to have potent antioxidant activity. Taken together, DLBS2411 is a promising novel agent for the management of dyspepsia, a condition of hyperacidity and diseases in the stomach requiring gastroprotection.

Tjandrawinata, Raymond R; Nailufar, Florensia; Arifin, Poppy F

2013-01-01

23

Antisecretory factor suppresses intestinal inflammation and hypersecretion  

PubMed Central

Background—Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin. ?Aims—To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa. ?Methods—Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 µg of toxin A or 3 µg of okadaic acid administered before or after injection of 0.1 µg of recombinant AF (rAF). ?Results—The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF. ?Conclusion—Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system. ?? Keywords: okadaic acid; Clostridium difficile toxin A; diarrhoea; neuropeptide; S5a; rat

Johansson, E; Jennische, E; Lange, S; Lonnroth, I

1997-01-01

24

A pioneer study on the anti-ulcer activities of copper nicotinate complex [CuCl (HNA)2] in experimental gastric ulcer induced by aspirin-pylorus [corrected] ligation model (Shay model).  

PubMed

This study was planned to look for a more rational mechanism(s) that could explain the anti-ulcer activity of copper nicotinate complex, since the mechanism whereby it prevents ulceration still to be investigated. Ulcer and the preventive indexes were scored, mucin, juice volume, total acidity, luminal haemoglobin, total peroxide and total antioxidant as an oxidative stress index (OSI), as well as total DNA fragmentation (as an apoptotic marker) and its percentage ratio in the juice were evaluated. Results confirmed the antisecretory ability of copper nicotinate, as reflected from the significant reduction of gastric juice volume and acid output. Data confirmed also copper nicotinate has a gastrocytoprotective action against ulcer pathogenesis through; enhancement of mucin secretion, reduction each of ulcer index and the mucosal bleeding rate into the gastric lumen; antioxidant activity through scavenging reactive oxygen species (ROS); anti-apoptotic activity through attenuation of the DNA fragmentation in the ulcerous treated group when compared with each of control and aspirin ulcerous untreated groups. This study hypothesized; at least in part, aspirin in the acidic environment of gastric juice become un-ionized and freely penetrate the mucosal barrier reaching to gastric wall. Due to the weak basic nature of cytoplasm of gastric mucosal cells, it accumulates in high concentrations into mucosal cells, and yields a negatively charged anion that is unable to exit the cell. Thus, superficial or deeper erosions are produced and bleeding takes place, within minutes. PMID:18343628

Tuorkey, Muobarak Jaber F-A; Abdul-Aziz, Karolin Kamel

2008-02-21

25

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

26

The effect of omeprazole on gastric myoelectrical activity and emptying.  

PubMed

Omeprazole, a proton pump inhibitor, is widely used for the treatment of patients with peptic ulcer, gastroesophageal reflux disease and functional dyspepsia (FD), although some studies have demonstrated that omeprazole delays gastric emptying. The purpose of this study was to investigate the efficacy of omeprazole on gastric motility including gastric myoelectrical activity and gastric emptying. This study was performed on 12 healthy volunteers. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi-solid meals using the (13)C-acetic acid breath test. EGG and gastric emptying were measured before and after treatment with 20 mg omeprazole orally for 7 days. In the fasting state, the percentage of EGG normogastria increased significantly compared to the baseline. No significant changes were observed in other EGG parameters including the percentage of tachygastria and bradygastria in both fasting and postprandial states, and the power ratios between both before and after ingestion of omeprazole. In addition, administrated omeprazole did not show any significant differences in the gastric emptying parameters such as the half emptying time. We conclude that administration of omeprazole did not affect gastric motility but improved gastric myoelectrical activity. These effects of omeprazole may be one of the mechanisms involved in its efficacy in relieving dyspeptic symptoms in FD patients. PMID:21979407

Kamiya, Takeshi; Shikano, Michiko; Tanaka, Mamoru; Tsukamoto, Hironobu; Ebi, Masahide; Hirata, Yoshikazu; Mizushima, Takashi; Murakami, Kenji; Shimura, Takaya; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi; Kato, Takashi; Imaeda, Kenro; Kataoka, Hiromi; Joh, Takashi

2011-01-01

27

Some pitfalls in antisecretory drug trials  

Microsoft Academic Search

A standard anticholinergic drug was compared to a sustained-release preparation of the same agent. Two 6-hr. doses of glycopyrrolate were equivalent to one dose of a glycopyrrolate Extentab in suppressing basal gastric secretion in subjects with acid-peptic disease.

John G. Moore; Edwin Englert

1967-01-01

28

Activation-Induced Cytidine Deaminase Expression in Gastric Cancer  

Microsoft Academic Search

Helicobacter pylori increases the risk of gastric cancer development and triggers aberrant expression of activation-induced cytidine deaminase (AID). The goal of the present study was to investigate whether AID expression is involved in the development or progression of gastric cancer and the nuclear expression of p53 protein in cancer cells. We examined the expression pattern of the AID and p53

Chang Jae Kim; Jae Hwi Song; Yong Gu Cho; Zhang Cao; Su Young Kim; Suk Woo Nam; Jung Young Lee; Won Sang Park

2007-01-01

29

Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels  

PubMed Central

Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signaling processes involved in intestinal fluid transport. Using cell lines and measurement procedures to isolate the effects on individual membrane transport proteins, crofelemer at 50 ?M had little or no effect on the activity of epithelial Na+ or K+ channels or on cAMP or calcium signaling. Crofelemer inhibited the cystic fibrosis transmembrane regulator (CFTR) Cl? channel with maximum inhibition of ?60% and an IC50 ?7 ?M. Crofelemer action at an extracellular site on CFTR produced voltage-independent block with stabilization of the channel closed state. Crofelemer did not affect the potency of glycine hydrazide or thiazolidinone CFTR inhibitors. Crofelemer action resisted washout, with <50% reversal of CFTR inhibition after 4 h. Crofelemer was also found to strongly inhibit the intestinal calcium-activated Cl? channel TMEM16A by a voltage-independent inhibition mechanism with maximum inhibition >90% and IC50 ?6.5 ?M. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl? channels may account for its intestinal antisecretory activity.

Tradtrantip, Lukmanee; Namkung, Wan

2010-01-01

30

Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.  

PubMed

Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signaling processes involved in intestinal fluid transport. Using cell lines and measurement procedures to isolate the effects on individual membrane transport proteins, crofelemer at 50 microM had little or no effect on the activity of epithelial Na(+) or K(+) channels or on cAMP or calcium signaling. Crofelemer inhibited the cystic fibrosis transmembrane regulator (CFTR) Cl(-) channel with maximum inhibition of approximately 60% and an IC(50) approximately 7 microM. Crofelemer action at an extracellular site on CFTR produced voltage-independent block with stabilization of the channel closed state. Crofelemer did not affect the potency of glycine hydrazide or thiazolidinone CFTR inhibitors. Crofelemer action resisted washout, with <50% reversal of CFTR inhibition after 4 h. Crofelemer was also found to strongly inhibit the intestinal calcium-activated Cl(-) channel TMEM16A by a voltage-independent inhibition mechanism with maximum inhibition >90% and IC(50) approximately 6.5 microM. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl(-) channels may account for its intestinal antisecretory activity. PMID:19808995

Tradtrantip, Lukmanee; Namkung, Wan; Verkman, A S

2009-10-06

31

Structure-activity relationship of dermorphin on gastric secretion.  

PubMed

The amphibian skin heptapeptide dermorphin (DM) administered intracerebroventricularly to rats significantly reduces gastric secretion. Dermorphin and 19 DM homologs and analogs were tested for their effect on gastric volume, pH, H+ ion concentration, and gastric acid output. DM, DM N-terminal pentapeptide and tetrapeptide amides, [D-Met2]DM, [Sar4]DM, [Trp5]DM, [Phe5]DM, [Gly7]DM, [Ser(Bzl)7]DM, and deamidated-DM significantly (P less than 0.01) reduced gastric acid output 2 h after injection. These data provide evidence for the following conclusions on the effect of DM on gastric secretion: ability to inhibit gastric secretion depends on the presence of the D-isomer of Ala at position 2, since [L-Ala2]DM is inactive; the shortest sequence with significant bioactivity is DM N-terminal tetrapeptide amide; the single replacement of amino acid residues in DM elicits a wide range of activities, varying from full biological activity of [Gly7]DM to those analogs with a complete lack of activity, such as [Pro4]DM and [Gly6]DM; and 4) coupling of protective groups to amino and hydroxyl groups of DM results in a significant loss of activity. PMID:3569127

Guglietta, A; Irons, B J; Lazarus, L H; Melchiorri, P

1987-05-01

32

Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats  

Microsoft Academic Search

Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin\\/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle. The PAR-2-activating peptide SLIGRL-NH2, but not the inactive control peptide,

Hiroyuki Nishikawa; Kenzo Kawai; Sachiyo Nishimura; Shuichi Tanaka; Hiromasa Araki; Bahjat Al-Ani; Morley D Hollenberg; Ryotaro Kuroda; Atsufumi Kawabata

2002-01-01

33

Effect of ZnSO4 upon gastric acid secretion and carbonic anhydrase.  

PubMed

Starting from the multiple role zinc holds in the enzymatic processes of the body and from some positive data concerning treatment with zinc sulphate in gastric ulcer, we have studied the effect of ZnSO4 on gastric acid secretion in duodenal ulcer patients, as well as that on purified and gastric mucosa carbonic anhydrase. Gastric secretory testing showed that zinc sulphate administered in doses of 60 ml/day (1% solution) for 10 days reduced basal acid secretion in duodenal ulcer patients by 57.7%. In vitro, concentrations of ZnSO4 ranging between 10(-6) and 10(-2)M, inhibit purified carbonic anhydrase activity in a dose-dependent manner, reaching maximum effect at 10(-2)M, when carbonic anhydrase activity dropped from 2060 +/- 65 IU to 660 +/- 85 IU. A similar dose-dependent inhibition was found with gastric mucosa carbonic anhydrase activity, where ZnSO4 at 10(-2)M reduces enzyme activity from its basal value of 1.58 +/- 0.36 EU/mg to 0.88 +/- 0.21 EU/mg. Besides this effect, zinc sulphate antagonized in vitro the activation of both purified and gastric mucosa carbonic anhydrase by histamine. In conclusion, the mechanism of antisecretory effect of ZnSO4 might well be the inhibition of the carbonic anhydrase in the gastric mucosa. PMID:4077313

Puscas, I; Sturzu, L; Búzás, G

1985-11-01

34

The acetone soluble fraction from bark extract of Stryphnodendron adstringens (Mart.) coville inhibits gastric acid secretion and experimental gastric ulceration in rats.  

PubMed

The acetone soluble fraction from a crude methanol extract of Stryphnodendron adstringens stem bark (AFSAB) was evaluated in acute (ethanol, indomethacin and hypothermic restraint-stress) and chronic (acetic acid) models of gastric ulceration and on basal and bethanechol-stimulated gastric acid secretion in rats. Rats pretreated orally with AFSAB at doses of 400 and 800 mg/kg showed significant decreases of gastric lesion scores in ethanol (62% and 98%) and hypothermic restraint-stress (89% and 88%) models but exerted no significant influence on indomethacin-induced acute or acetic acid-induced chronic ulceration. In pylorus-ligated rats, AFSAB significantly decreased the basal as well as bethanechol-stimulated gastric secretory volume and the total acidity with an elevated pH value. AFSAB failed to modify the gastric mucus and the gastric wall nonprotein-sulphydryl content. These results point to a possible antisecretory effect of AFSAB which account for the observed antiulcer activity in ethanol and hypothermic restraint-stress induced models of acute gastric ulceration. PMID:12203261

Martins, D T O; Lima, J C S; Rao, V S N

2002-08-01

35

Adenosine deaminase, 5?-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis  

Microsoft Academic Search

Adenosine deaminase (ADA), 5?-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. Enzyme activities were given as units per ml gastric juice and units per mg protein in gastric juice. ADA, 5NT and XO activities were found lower and protein

Ilker Durak; Necati Örmeci; Ömer Akyol; Orhan Canbolat; Mustafa Kavutçu; Mahmut Bülbül

1994-01-01

36

Effects of the selective I1 imidazoline receptor agonist, moxonidine, on gastric secretion and gastric mucosal injury in rats.  

PubMed Central

1. Previous reports of the effects of alpha 2-adrenoceptor stimulation on gastric secretion are inconsistent because it was not clear whether the compounds were activating alpha 2-adrenoceptors and/or newly described imidazoline receptors. In the present experiments, the effects of moxonidine, an I1-imidazoline receptor agonist and antihypertensive agent, on gastric secretion and on experimental gastric mucosal injury were examined. 2. Moxonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) potently inhibited basal (non-stimulated) gastric acid secretion in conscious rats with an ED50 of 0.04 mg kg-1. Two hours following administration of the highest dose of moxonidine (1.0 mg kg-1), gastric acid output was completely suppressed. Moxonidine also significantly increased intragastric pH, at the two highest doses. 3. The alpha 2-adrenoceptor agonist, clonidine (0.01, 0.1 and 1.0 mg kg-1, i.p.) decreased basal acid secretion at the lowest dose (37%) and at the highest dose (46%), while the intermediate dose did not affect gastric acid output. 4. In an ethanol-induced model of gastric mucosal injury, moxonidine decreased the length of lesions at the lowest and highest doses (0.01 and 1.0 mg kg-1) as well as the number of the lesions, at the highest dose (1.0 mg kg-1). 5. In pylorus-ligated rats, moxonidine significantly decreased acid secretion (all doses), total secretory volume (1.0 mg kg-1) as well as pepsin output (1.0 mg kg-1). 6. In comparison to clonidine, moxonidine appears to be a more potent anti-secretory and gastric-protective compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Glavin, G B; Smyth, D D

1995-01-01

37

Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.  

PubMed Central

The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth.

Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

1994-01-01

38

Plasminogen activator inhibitor (PAI)-1 suppresses inhibition of gastric emptying by cholecystokinin (CCK) in mice.  

PubMed

The intestinal hormone cholecystokinin (CCK) delays gastric emptying and inhibits food intake by actions on vagal afferent neurons. Recent studies suggest plasminogen activator inhibitor (PAI)-1 suppresses the effect of CCK on food intake. In this study we asked whether PAI-1 also modulated CCK effects on gastric emptying. Five minute gastric emptying of liquid test meals was studied in conscious wild type mice (C57BL/6) and in transgenic mice over-expressing PAI-1 in gastric parietal cells (PAI-1H/K? mice), or null for PAI-1. The effects of exogenous PAI-1 and CCK8s on gastric emptying were studied after ip administration. Intragastric peptone delayed gastric emptying in C57BL/6 mice by a mechanism sensitive to the CCK-1 receptor antagonist lorglumide. Peptone did not delay gastric emptying in PAI-1-H/K? mice. Exogenous CCK delayed gastric emptying of a control test meal in C57BL/6 mice and this was attenuated by administration of PAI-1; exogenous CCK had no effect on emptying in PAI-1-H/K? mice. Prior administration of gastrin to increase gastric PAI-1 inhibited CCK-dependent effects on gastric emptying in C57BL/6 mice but not in PAI-1 null mice. Thus, both endogenous and exogenous PAI-1 inhibit the effects of CCK (whether exogenous or endogenous) on gastric emptying. The data are compatible with emerging evidence that gastric PAI-1 modulates vagal effects of CCK. PMID:23816469

Gamble, Joanne; Kenny, Susan; Dockray, Graham J

2013-06-28

39

Helicobacter pylori Activates Gastric Epithelial Cells to Produce Interleukin8 via Protease-Activated Receptor 2  

Microsoft Academic Search

Background\\/Aim: Recently, it has been shown that serine proteases derived from microorganisms stimulate epithelial cells to produce inflammatory mediators through protease-activated receptor (PAR). We investigated the involvement of PAR2 in the interleukin (IL)-8 production by Helicobacter pylori-infected gastric epithelial cells. Methods and Results: Human gastric epithelial cells, MKN45 cells, were used. The expression of PAR2 was assessed by real-time PCR

Hirokazu Kajikawa; Norimasa Yoshida; Kazuhiro Katada; Fumihiro Hirayama; Osamu Handa; Satoshi Kokura; Yuji Naito; Toshikazu Yoshikawa

2007-01-01

40

Rebamipide Decreases the Susceptibility of Gastric Mucosa to Acid-Induced Injury in Rats by Inhibiting Neutrophil Activation  

Microsoft Academic Search

We previously demonstrated that activated neutrophils increased the susceptibility of gastric mucosa to acid-induced injury in rats. As rebamipide, an anti-ulcer agent, inhibits neutrophil activation, we examined whether the rebamipide reduces stress-induced gastric mucosal injury by decreasing susceptibility to acid-induced gastric mucosal injury in rats. Increase in both gastric mucosal permeability and gastric microvascular permeability evaluated by 51Cr-EDTA clearance and

Naoaki Harada; Kenji Okajima; Wenge Liu

2005-01-01

41

Gastric myoelectrical activity in patients with primary biliary cirrhosis  

Microsoft Academic Search

Objective  To examine gastric myoelectrical activity in patients with primary biliary cirrhosis (PBC).\\u000a \\u000a \\u000a \\u000a Materials and methods  The study comprised 11 female PBC patients (average age 53.4 years, range 43–70) and two aged-matched control groups: 11 (53.4 years,\\u000a range 37–78) healthy women, and 10 female patients with chronic hepatitis C, CHC (53.9 years, range 35–66), who were examined\\u000a prior to administration of an antiviral therapy. Every

Anna Kasicka-Jonderko; Beata Krusiec-?widergo?; Krzysztof Jonderko; Joanna Musialik; Maciej Gonciarz; Barbara B?o?ska-Fajfrowska; Zbigniew Gonciarz

2009-01-01

42

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress  

PubMed Central

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis. RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro. In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro. Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.

Singh, Laishram Pradeepkumar; Mishra, Amartya; Saha, Debjit; Swarnakar, Snehasikta

2011-01-01

43

Inhibitory Reflexive Effect of Rectal Distension on Postprandial Gastric Myoelectrical Activity  

Microsoft Academic Search

The aim of the study was to determine the effects of low-volume rectal distension on gastric myoelectrical activity. The study was performed in 14 healthy volunteers in 2 randomized sessions. In the control session, a small balloon was inserted into the rectum 10 cm beyond the anal verge and inflated with 20 ml of air. Gastric myoelectrical activity was recorded

Liwei Qian; William C. Orr; J. D. Z. Chen

2002-01-01

44

Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer.  

PubMed

Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. Taken together, these results suggest that HGF may play a pivotal role in the regulatory circuit between gastric cancer cells and stromal fibroblasts, and neutralization of HGF inhibits both activation and tumor-promoting properties of CAFs. PMID:23402812

Wu, Xiongyan; Chen, Xuehua; Zhou, Quan; Li, Pu; Yu, Beiqin; Li, Jianfang; Qu, Ying; Yan, Jun; Yu, Yingyan; Yan, Min; Zhu, Zhenggang; Liu, Bingya; Su, Liping

2013-02-09

45

Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats  

PubMed Central

The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE2 production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes.

Luiz-Ferreira, Anderson; Cola, Maira; Barbastefano, Victor; de-Faria, Felipe Meira; de Almeida, Ana Beatriz A.; Farias-Silva, Elisangela; Calvo, Tamara Regina; Hiruma-Lima, Clelia A.; Vilegas, Wagner; Souza-Brito, Alba Regina M.

2012-01-01

46

Structure-activity relationships of eighteen somatostatin analogues on gastric secretion.  

PubMed Central

1. The effect of somatostatin and eighteen somatostatin analogues on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 microgram kg-1 hr-1 was found to be 1.29 +/- 0.13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp8 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-simatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.

Brown, M P; Coy, D H; Gomez-Pan, A; Hirst, B H; Hunter, M; Meyers, C; Reed, J D; Schally, A V; Shaw, B

1978-01-01

47

Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptor? Activation  

PubMed Central

Peroxisome proliferator-activated receptor? (PPAR?) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPAR? agonists to promote tumorigenesis in some organs. In the present study, we describe a new gastric tumor mouse model that is dependent on the potent and highly selective PPAR? agonist GW501516 following carcinogen administration. The progression of gastric tumorigenesis was rapid as determined by magnetic resonance imaging and resulted in highly metastatic squamous cell carcinomas of the forestomach within two months. Tumorigenesis was associated with gene expression signatures indicative of cell adhesion, invasion, inflammation, and metabolism. Increased PPAR? expression in tumors correlated with increased PDK1, Akt, ?-catenin, and S100A9 expression. The rapid development of metastatic gastric tumors in this model will be useful for evaluating preventive and therapeutic interventions in this disease.

Pollock, Claire B.; Rodriguez, Olga; Martin, Philip L.; Albanese, Chris; Li, Xin; Kopelovich, Levy; Glazer, Robert I.

2010-01-01

48

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

2008-05-18

49

Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats.  

PubMed

In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound's inhibitory effect on acetylcholinesterase (AChE) activity derived from rat stomach. In in vivo studies, acotiamide (30 and 100mg/kg s.c.) and itopride (100mg/kg s.c.) markedly enhanced normal gastric antral motility in rats. In gastric motility dysfunction models, acotiamide (100mg/kg s.c.) and itopride (100mg/kg s.c.) improved both gastric antral hypomotility and the delayed gastric emptying induced by clonidine, an ?(2)-adrenoceptor agonist. In contrast, mosapride (10mg/kg s.c.) had no effect on these models. Like the AChE inhibitors itopride (30 mg/kg s.c.) and neostigmine (10 ?g/kg s.c.), acotiamide (10mg/kg s.c.) also clearly enhanced gastric body contractions induced by electrical stimulation of the vagus, which were abolished by atropine and hexamethonium, whereas mosapride (3 and 10mg/kg s.c.) did not. In in vitro studies, acotiamide concentration-dependently inhibited rat stomach-derived AChE activity (IC(50)=2.3 ?mol/l). In addition, stomach tissue concentrations of acotiamide after administration at 10mg/kg s.c. were sufficient to produce inhibition of AChE activity in rat stomach. These results suggest that acotiamide stimulates gastric motility and improves gastric motility dysfunction in rats by inhibiting AChE activity, and may suggest a role for acotiamide in improving gastric motility dysfunction in patients with functional dyspepsia. PMID:21651906

Kawachi, Masanao; Matsunaga, Yugo; Tanaka, Takao; Hori, Yuko; Ito, Katsunori; Nagahama, Kenji; Ozaki, Tomoko; Inoue, Naonori; Toda, Ryoko; Yoshii, Kazuyoshi; Hirayama, Masamichi; Kawabata, Yoshihiro; Takei, Mineo

2011-06-01

50

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

51

Role of platelet activating factor on the fibrinolytic activation in the pathogenesis of gastric mucosal damage induced by endothelin-1  

Microsoft Academic Search

We have examined the hypothesis that the release of tissue type plasminogen activator may play a prominent role in endothelin induced gastric mucosal injury. We determined tissue type plasminogen activator activity in the regional blood sample and the concentration of platelet activating factor in the gastric mucosa after the administration of endothelin-1 in a range of 50-500 pmol\\/kg into the

I Kurose; S Miura; D Fukumura; H Tashiro; H Imaeda; H Shiozaki; M Suematsu; H Nagata; E Sekizuka; M Tsuchiya

1992-01-01

52

Disturbances of Gastric Electrical Control Activity after Laparotomic Cholecystectomy Are Related to Interleukin6 Concentrations  

Microsoft Academic Search

Background: The aim of the present study was to characterize the disturbances of gastric electrical control activity after cholecystectomy and to correlate electrogastrographic (EGG) findings with inflammatory markers. Patients and Methods: 52 adult patients were examined in conjunction with planned laparotomic or laparoscopic cholecystectomy. Gastric myoelectrical activity was recorded with a MicroDigitrapper device using three Ag-AgCl disposable skin electrodes. The

P. Maruna; R. Frasko; J. Lindner

2009-01-01

53

Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice  

PubMed Central

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostanoid biosynthesis, plays a key role in gastrointestinal carcinogenesis. Among various prostanoids, prostaglandin E2 (PGE2) appears to be most responsible for cancer development. To investigate the role of PGE2 in gastric tumorigenesis, we constructed transgenic mice simultaneously expressing COX-2 and microsomal prostaglandin E synthase (mPGES)-1 in the gastric epithelial cells. The transgenic mice developed metaplasia, hyperplasia and tumorous growths in the glandular stomach with heavy macrophage infiltrations. Although gastric bacterial counts in the transgenic mice were within the normal range, treatment with antibiotics significantly suppressed activation of the macrophages and tumorous hyperplasia. Importantly, the antibiotics treatment did not affect the macrophage accumulation. Notably, treatment of the transgenic mice with lipopolysaccharides induced proinflammatory cytokines through Toll-like receptor 4 in the gastric epithelial cells. These results indicate that an increased level of PGE2 enhances macrophage infiltration, and that they are activated through epithelial cells by the gastric flora, resulting in gastric metaplasia and tumorous growth. Furthermore, Helicobacter infection upregulated epithelial PGE2 production, suggesting that the COX-2/mPGES-1 pathway contributes to the Helicobacter-associated gastric tumorigenesis.

Oshima, Hiroko; Oshima, Masanobu; Inaba, Kayo; Taketo, Makoto M

2004-01-01

54

Insulin-Induced Hypoglycemia Stimulates Gastric Vagal Activity and Motor Function without Increasing Cardiac Vagal Activity  

Microsoft Academic Search

Background\\/Aims: We investigated whether increasing the efferent vagal activity by insulin-induced hypoglycemia would enhance gastric emptying and volumes in healthy subjects. Methods: Twenty healthy volunteers (10 males) were examined with and without vagal stimulation by insulin-induced hypoglycemia using a glucose clamp technique. Stomach function was tested by drinking meat soup (0.04 kcal ml–1) at a rate of 100 ml min–1

Ina Elen Hjelland; Nils Petter Oveland; Katrine Leversen; Arnold Berstad; Trygve Hausken

2005-01-01

55

Proliferative activity of epithelium of the surface and pits of the gastric mucosa after aspirin injury  

Microsoft Academic Search

The proliferative activity of the surface epithelium of the gastric mucosa and the epithelium of the gastric pits in albino mice was studied after injury by aspirin (200 mg\\/kg). An intraperitoneal injection of3H-thymidine was given to all the animals 1 h before sacrifice. The mitotic index and index of labeled nuclei were counted on autoradiographs 3, 10, and 20 days

G. V. Tsodikov; V. V. Klimenko; S. N. Laz'kova

1979-01-01

56

The comparative gastric ulcerogenic activities of non-steroid anti-inflammatory drugs  

Microsoft Academic Search

A new gastric assay was employed to screen for the ulcerogenic activity of non-steroid anti-inflammatory (NSAI) analgesic drugs. The technique involves exposing rats to brief periods of cold stress, which is not itself sufficient to cause mucosal damage, but does specifically sensitize the stomach to irritant or ulcerogenic actions of NSAI drugs. The assessment of gastric ulcerogenicity of some well-known

K. D. Rainsford

1977-01-01

57

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

PubMed

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. PMID:23494120

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

2013-03-14

58

Activation of Wnt signaling inhibits the pro-apoptotic role of Notch in gastric cancer cells.  

PubMed

Notch and Wnt signaling play critical roles in the regulation of development and diseases. Several studies have previously reported that Notch may be a therapeutic target in the treatment of various types of human cancer. In this study, we report that activation of Notch1 inhibits the proliferation of BGC-823 gastric cancer cells. However, the activation of the Wnt/??catenin signaling pathway promotes the growth of BGC-823 cells. Furthermore, the combinational activation of the two signaling pathways promotes the proliferation of BGC-823 cells. These data suggest that the activation of Wnt signaling overcomes the pro-apoptotic role of Notch in BGC-823 gastric cancer cells. PMID:23563575

Li, Hong; Mo, Juan; Jia, Guizhi; Liu, Chao; Luan, Zhidong; Guan, Yifu

2013-04-03

59

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

60

Physical activity and physical function changes in obese individuals after gastric bypass surgery  

Microsoft Academic Search

BackgroundLittle is known about the effects of gastric bypass surgery (GBS) on physical activity and physical function. We examined the physical activity, physical function, psychosocial correlates to physical activity participation, and health-related quality of life of patients before and after GBS.

Deborah A. Josbeno; John M. Jakicic; Andrea Hergenroeder; George M. Eid

2010-01-01

61

Rebamipide Attenuates Indomethacin-Induced Gastric Mucosal Lesion Formation by Inhibiting Activation of Leukocytes in Rats  

Microsoft Academic Search

Granulocyte elastase released from activatedleukocytes plays an important role in leukocyteinfiltration. Since activated leukocytes have been shownto be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidalantiinflammatory drugs, inhibition of granulocyteelastase release from activated leukocytes may be usefulin the prevention of these lesions. Rebamipide, a novel antiulcer agent, inhibited granulocyte elastaserelease from activated neutrophils in vitro. Rebamipideand

Kazunori Murakami; Kenji Okajima; Mitsuhiro Uchiba; Naoaki Harada; Masayoshi Johno; Hiroaki Okabe; Kiyoshi Takatsuki

1997-01-01

62

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

63

Ca Activated K+ Channel Kca3.1 as a Determinant of Gastric Acid Secretion  

Microsoft Academic Search

The Ca2+ activated K+ channel Kca3.1 is expressed in a variety of tissues. In the gastric gland it is expressed in the basolateral cell membrane. To determine the functional significance of Kca3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional Kca3.1 (Kca3.1-\\/-) and from their wild type littermates (Kca3.1+\\/+).

Anand Rotte; Venkanna Pasham; Andreas F. Mack; Madhuri Bhandaru; Syed M. Qadri; Melanie Eichenmüller; Peter Ruth; Florian Lang

2011-01-01

64

Ca2+ Activated K+ Channel Kca3.1 as a Determinant of Gastric Acid Secretion  

Microsoft Academic Search

The Ca2+ activated K+ channel Kca3.1 is expressed in a variety of tissues. In the gastric gland it is expressed in the basolateral cell membrane. To determine the functional significance of Kca3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional Kca3.1 (Kca3.1-\\/-) and from their wild type littermates (Kca3.1+\\/+).

Anand Rotte; Venkanna Pasham; Andreas F. Mack; Madhuri Bhandaru; Syed M. Qadri; Melanie Eichenmüller; Peter Ruth; Florian Lang

2011-01-01

65

Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa  

Microsoft Academic Search

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Our previous study demonstrated increased ERK activation and MAP kinase phosphatase-1 (MKP-1) overexpression in PHT gastric mucosa. However, it remains unknown which tyrosine kinase receptors are involved in ERK activation and whether ERK activation results in increased cell proliferation. We examined whether EGF receptor (EGF-R) is

Hirofumi Kawanaka; Morimasa Tomikawa; Dolgor Baatar; Michael K. Jones; Rama Pai; Imre L. Szabo; Keizo Sugimachi; I. James Sarfeh; Andrzej S. Tarnawski

2001-01-01

66

Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer  

PubMed Central

Background The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer. Methods The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines. Results Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53. Conclusions In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.

2010-01-01

67

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

68

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

PubMed

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 PGE? 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 E? (PGE?) 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. PMID:22611307

Takeuchi, Koji

2012-05-14

69

Biomarkers for antitumor activity of bevacizumab in gastric cancer models  

PubMed Central

Background Bevacizumab is a humanized monoclonal antibody to human vascular endothelial cell growth factor (VEGF) and has been used for many types of cancers such as colorectal cancer, non-small cell lung cancer, breast cancer, and glioblastoma. Bevacizumab might be effective against gastric cancer, because VEGF has been reported to be involved in the development of gastric cancer as well as other cancers. On the other hand, there are no established biomarkers to predict the bevacizumab efficacy in spite of clinical needs. Therefore, we tried to identify the predictive markers for efficacy of bevacizumab in gastric cancer patients by using bevacizumab-sensitive and insensitive tumor models. Methods Nine human gastric and two colorectal cancer mouse xenografts were examined for their sensitivity to bevacizumab. We examined expression levels of angiogenic factors by ELISA, bioactivity of VEGF by phosphorylation of VEGFR2 in HUVEC after addition of tumor homogenate, tumor microvessel density by CD31-immunostaining, and polymorphisms of the VEGF gene by HybriProbe™ assay. Results Of the 9 human gastric cancer xenograft models used, GXF97, MKN-45, MKN-28, 4-1ST, SC-08-JCK, and SC-09-JCK were bevacizumab-sensitive, whereas SCH, SC-10-JCK, and NCI-N87 were insensitive. The sensitivity of the gastric cancer model to bevacizumab was not related to histological type or HER2 status. All tumors with high levels of VEGF were bevacizumab-sensitive except for one, SC-10-JCK, which had high levels of VEGF. The reason for the refractoriness was non-bioactivity on the phosphorylation of VEGFR2 and micro-vessel formation of VEGF, but was not explained by the VEGF allele or VEGF165b. We also examined the expression levels of other angiogenic factors in the 11 gastrointestinal tumor tissues. In the refractory models including SC-10-JCK, tumor levels of another angiogenic factor, bFGF, were relatively high. The VEGF/bFGF ratio correlated more closely with sensitivity to bevacizumab than with the VEGF level. Conclusions VEGF levels and VEGF/bFGF ratios in tumors were related to bevacizumab sensitivity of the xenografts tested. Further clinical investigation into useful predictive markers for bevacizumab sensitivity is warranted.

2012-01-01

70

Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats  

Microsoft Academic Search

In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound's inhibitory effect on acetylcholinesterase (AChE) activity derived from rat

Masanao Kawachi; Yugo Matsunaga; Takao Tanaka; Yuko Hori; Katsunori Ito; Kenji Nagahama; Tomoko Ozaki; Naonori Inoue; Ryoko Toda; Kazuyoshi Yoshii; Masamichi Hirayama; Yoshihiro Kawabata; Mineo Takei

2011-01-01

71

Diamine oxidase activity in gastric and duodenal mucosa of man and other mammals with special reference to the pyloric junction  

Microsoft Academic Search

In the gastric mucosa of human subjects and of various mammals methylation was accepted as the main pathway of histamine catabolism. However, augmentation of gastric acid secretion by aminoguanidine, the strong inhibitor of diamine oxidase, indicated an influence of diamine oxidase activity on this secretory process. Therefore a careful reinvestigation of the occurrence of diamine oxidase activity was started from

J. Kusche; W. Lorenz; C.-D. Stahlknecht; A. Friedrich; A. Schmidt; K. Boo; G. Reichert

1978-01-01

72

Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats  

Microsoft Academic Search

The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric erosions and concentration of lipid peroxides in the gastric mucosa increased with time after administration of indomethacin (20 mg\\/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significantly decreased and

T Yoshikawa; Y Naito; A Kishi; T Tomii; T Kaneko; S Iinuma; H Ichikawa; M Yasuda; S Takahashi; M Kondo

1993-01-01

73

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

74

Effects of Rebamipide, a Novel Anti-Ulcer Agent, on Gastric Mucosal Injury Induced by Platelet-Activating Factor in Rats  

Microsoft Academic Search

We examined the role of gastric mucosal bloodflow, lipid peroxidation, and neutrophil accumulationmediated by platelet-activating factor in the protectiveeffect of rebamipide against gastric mucosal injury in rats. The intravenous injection ofplatelet-activating factor induced hyperemia andhemorrhagic erosions in rat stomachs. Rebamipide did notaffect the decrease in the gastric mucosal blood flow induced by platelet-activating factor. Theincrease in gastric injury score afterplatelet-activating

Satoshi Kokura; Toshikazu Yoshikawa; Yuji Naito; Hiroshi Ichikawa; Hirohisa Takano; Shuji Takahashi; Takashi Tomii; Norimasa Yoshida; Motoharu Kondo

1997-01-01

75

Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells  

PubMed Central

The gastric pathogen Helicobacter pylori (H. pylori) is linked to peptic ulcer and gastric cancer, but the relevant pathophysiological mechanisms are unclear. We now report that H. pylori stimulates the expression of plasminogen activator inhibitor (PAI)-1, urokinase plasminogen activator (uPA), and its receptor (uPAR) in gastric epithelial cells and the consequences for epithelial cell proliferation. Real-time PCR of biopsies from gastric corpus, but not antrum, showed significantly increased PAI-1, uPA, and uPAR in H. pylori-positive patients. Transfection of primary human gastric epithelial cells with uPA, PAI-1, or uPAR promoters in luciferase reporter constructs revealed expression of all three in H+/K+ATPase- and vesicular monoamine transporter 2-expressing cells; uPA was also expressed in pepsinogen- and uPAR-containing trefoil peptide-1-expressing cells. In each case expression was increased in response to H. pylori and for uPA, but not PAI-1 or uPAR, required the virulence factor CagE. H. pylori also stimulated soluble and cell surface-bound uPA activity, and both were further increased by PAI-1 knockdown, consistent with PAI-1 inhibition of endogenous uPA. H. pylori stimulated epithelial cell proliferation, which was inhibited by uPA immunoneutralization and uPAR knockdown; exogenous uPA also stimulated proliferation that was further increased after PAI-1 knockdown. The proliferative effects of uPA were inhibited by immunoneutralization of the EGF receptor and of heparin-binding EGF (HB-EGF) by the mutant diphtheria toxin CRM197 and an EGF receptor tyrosine kinase inhibitor. H. pylori induction of uPA therefore leads to epithelial proliferation through activation of HB-EGF and is normally inhibited by concomitant induction of PAI-1; treatments directed at inhibition of uPA may slow the progression to gastric cancer.

Kenny, Susan; Duval, Cedric; Sammut, Stephen J.; Steele, Islay; Pritchard, D. Mark; Atherton, John C.; Argent, Richard H.; Dimaline, Rod; Dockray, Graham J.; Varro, Andrea

2008-01-01

76

Gastric peroxisome proliferator activator receptor-? expression and cytoprotective actions of its ligands against ischemia-reperfusion injury in rats  

PubMed Central

The beneficial effects by peroxisome proliferator-activated receptor-? (PPAR-?) on gastric injury induced by ischemia-reperfusion have been confirmed, however, the precise mechanism of its cytoprotection is not elucidated thoroughly. The aim of the present study was to determine the gastric localization of PPAR-? expression in the rat gastric mucosa, and to clarify the mechanism of its cytoprotective properties. The gastric expression of PPAR-? was confirmed by RT-PCR and western blot, and localized on gastric epithelial cells. The protective effect of PPAR-? ligands, pioglitazone or 15-deoxy-?12,14-prostaglandin J2, on gastric ischemia-reperfusion injury was reversed by the co-administration with PPAR-? antagonist. The gastric expression of tumor necrosis factor-? and cytokine-induced neutrophil chemoattractant-1 increased significantly in rats treated ischemia-reperfusion, and these increases were significantly inhibited by treatment with pioglitazone. Among the 1,032 probes, 18 probes were up-regulated at least 1.5-fold, 17 were down-regulated at least 1.5-fold by pioglitazone. The network including calnexin, endoplasmic reticulum stress protein, heat shock proteins, and proteasome genes was induced by pioglitazone treatment. In conclusion, activation of gastric epithelial PPAR-? receptor by its ligands may represent a novel therapeutic approach for gastric inflammation via up-regulation of heat shock proteins and endoplasmic reticulum-related proteins.

Naito, Yuji; Takagi, Tomohisa; Katada, Kazuhiro; Tomatsuri, Naoya; Mizushima, Katsura; Handa, Osamu; Kokura, Satoshi; Yagi, Nobuaki; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

2011-01-01

77

Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury.  

PubMed

Our previous studies demonstrated that ethanol injury triggers the angiogenic response in gastric mucosa bordering necrosis. The present study was aimed to determine whether vascular endothelial growth factor (VEGF) (a potent angiogenic peptide selectively acting on endothelial cells) and Ras (a mediator of cell proliferation and a putative regulator of VEGF expression) are involved in gastric angiogenesis after ethanol injury. We studied the angiogenic response and expression of VEGF and Ras in gastric mucosa after ethanol injury. Ethanol damage triggered 1) angiogenesis in the gastric mucosa bordering necrosis, 2) significant increases in VEGF mRNA and protein expression, and 3) significant increases in the expression of Ki-ras mRNA and Ras proteins. Neutralizing anti-VEGF antibody significantly reduced (by greater than threefold) the angiogenic response to ethanol-induced injury. Moreover, mevastatin, an inhibitor of Ras activation, completely blocked the induction of VEGF expression in cultured primary endothelial cells. Because, in other tissues, VEGF is one of the most potent angiogenic factors and VEGF expression is dependent on Ras, our data indicate that Ras and VEGF are involved in gastric mucosal angiogenesis after ethanol injury. PMID:10362637

Jones, M K; Itani, R M; Wang, H; Tomikawa, M; Sarfeh, I J; Szabo, S; Tarnawski, A S

1999-06-01

78

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

Microsoft Academic Search

BackgroundGastric 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

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

2009-01-01

79

AKT Activation and Telomerase Reverse Transcriptase Expression are Concurrently Associated with Prognosis of Gastric Cancer.  

PubMed

AKT is a protein in the phosphatidylinositol-3 kinase (PI3K) pathway and associated with diverse pro-tumoral responses. Activation of the human telomere reverse transcriptase (hTERT) is one of AKT's tumorigenic effects. In this study, the significance of AKT phosphorylation and hTERT on prognosis of gastric cancer were examined. AKT activation by epidermal growth factor increased hTERT expression and telomerase activity. In contrast, AKT inactivation by inhibitors and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric cancer cells. In 40 gastric cancer tissues, significant correlations were found among the levels of phosphorylated AKT (pAKT), hTERT expression, and telomer length. The pAKT levels or the levels of pAKT/hTERT were not associated with clinicopathological parameters, including stage and nodal metastasis. However, survival rates of the pAKT-high patients or the pAKT-high and hTERT-high patients were significantly poorer than those in other patients. These findings suggest that AKT and hTERT are good molecular targets for the treatment of gastric cancer. PMID:23969493

Sasaki, Takamitsu; Kuniyasu, Hiroki; Luo, Yi; Kitayoshi, Misaho; Tanabe, Eriko; Kato, Daisuke; Shinya, Satoshi; Fujii, Kiyomu; Ohmori, Hitoshi; Yamashita, Yuichi

2013-08-21

80

Antimicrobial activities of Eugenol and Cinnamaldehyde against the human gastric pathogen Helicobacter pylori  

Microsoft Academic Search

BACKGROUND: Eradication of Helicobacter pylori is an important objective in overcoming gastric diseases. Many regimens are currently available but none of them could achieve 100% success in eradication. Eugenol and cinnamaldehyde that are commonly used in various food preparations are known to possess antimicrobial activity against a wide spectrum of bacteria. AIM: The present study was performed to assess the

Shaik Mahaboob Ali; Aleem A Khan; Irshad Ahmed; M Musaddiq; Khaja S Ahmed; H Polasa; L Venkateswar Rao; Chittoor M Habibullah; Leonardo A Sechi; Niyaz Ahmed

2005-01-01

81

Systemic activation of K-ras rapidly induces gastric hyperplasia and metaplasia in mice.  

PubMed

Mouse models with conditional activation of K-ras (K-ras(G12D)) are used widely to investigate the role of oncogenic K-ras in a tissue-specific manner. However, the effect of ubiquitous activation of K-ras in adult mice has not been well studied. Herein, we report that systemic activation of K-ras in mice leads to rapid changes in gastric cellular homeostasis. Conditional activation of K-ras results in activation of the MAPK pathway and hyperproliferation of squamous epithelium in the forestomach and metaplasia in the glandular stomach. Parietal cells almost completely disappear from the upper part of the stomach adjacent to forestomach of K-ras activated mice. CDX2, a caudal-related homeobox transcription factor normally expressed in the intestine, is upregulated in parts of the stomach, following activation of K-ras in mice. Cyclooxygenase 2 (COX-2), a mediator of inflammation, is also upregulated in parts of the stomach of the K-ras activated mice with concomitant infiltration of hematopoietic cells in the hyperplastic tissue. Moreover, in K-ras activated mice, the expression of putative progenitor cell marker Dcamkl1 is upregulated in the glandular stomach. Expression of CD44, a candidate stomach cancer stem cell marker, is also increased in forestomach and the glandular stomach. These results suggest that cells of the stomach, potentially stem or progenitor cells, are highly susceptible to K-ras activation-induced initiation of gastric precancerous lesions. The histological changes in the K-ras activated mice resemble the pre-neoplastic changes that take place during gastric carcinogenesis in humans. Thus, a mouse model with systemic K-ras(G12D) activation could be useful for studying the early molecular events leading to gastric carcinogenesis. PMID:21761008

Matkar, Smita S; Durham, Amy; Brice, Angela; Wang, Timothy C; Rustgi, Anil K; Hua, Xianxin

2011-04-01

82

Systemic activation of K-ras rapidly induces gastric hyperplasia and metaplasia in mice  

PubMed Central

Mouse models with conditional activation of K-ras (K-rasG12D) are used widely to investigate the role of oncogenic K-ras in a tissue-specific manner. However, the effect of ubiquitous activation of K-ras in adult mice has not been well studied. Herein, we report that systemic activation of K-ras in mice leads to rapid changes in gastric cellular homeostasis. Conditional activation of K-ras results in activation of the MAPK pathway and hyperproliferation of squamous epithelium in the forestomach and metaplasia in the glandular stomach. Parietal cells almost completely disappear from the upper part of the stomach adjacent to forestomach of K-ras activated mice. CDX2, a caudal-related homeobox transcription factor normally expressed in the intestine, is upregulated in parts of the stomach, following activation of K-ras in mice. Cyclooxygenase 2 (COX-2), a mediator of inflammation, is also upregulated in parts of the stomach of the K-ras activated mice with concomitant infiltration of hematopoietic cells in the hyperplastic tissue. Moreover, in K-ras activated mice, the expression of putative progenitor cell marker Dcamkl1 is upregulated in the glandular stomach. Expression of CD44, a candidate stomach cancer stem cell marker, is also increased in forestomach and the glandular stomach. These results suggest that cells of the stomach, potentially stem or progenitor cells, are highly susceptible to K-ras activation-induced initiation of gastric precancerous lesions. The histological changes in the K-ras activated mice resemble the pre-neoplastic changes that take place during gastric carcinogenesis in humans. Thus, a mouse model with systemic K-rasG12D activation could be useful for studying the early molecular events leading to gastric carcinogenesis.

Matkar, Smita S; Durham, Amy; Brice, Angela; Wang, Timothy C; Rustgi, Anil K; Hua, Xianxin

2011-01-01

83

Convective washout reduces the antidiarrheal efficacy of enterocyte surface-targeted antisecretory drugs  

PubMed Central

Secretory diarrheas such as cholera are a major cause of morbidity and mortality in developing countries. We previously introduced the concept of antisecretory therapy for diarrhea using chloride channel inhibitors targeting the cystic fibrosis transmembrane conductance regulator channel pore on the extracellular surface of enterocytes. However, a concern with this strategy is that rapid fluid secretion could cause convective drug washout that would limit the efficacy of extracellularly targeted inhibitors. Here, we developed a convection–diffusion model of washout in an anatomically accurate three-dimensional model of human intestine comprising cylindrical crypts and villi secreting fluid into a central lumen. Input parameters included initial lumen flow and inhibitor concentration, inhibitor dissociation constant (Kd), crypt/villus secretion, and inhibitor diffusion. We modeled both membrane-impermeant and permeable inhibitors. The model predicted greatly reduced inhibitor efficacy for high crypt fluid secretion as occurs in cholera. We conclude that the antisecretory efficacy of an orally administered membrane-impermeant, surface-targeted inhibitor requires both (a) high inhibitor affinity (low nanomolar Kd) to obtain sufficiently high luminal inhibitor concentration (>100-fold Kd), and (b) sustained high luminal inhibitor concentration or slow inhibitor dissociation compared with oral administration frequency. Efficacy of a surface-targeted permeable inhibitor delivered from the blood requires high inhibitor permeability and blood concentration (relative to Kd).

Jin, Byung-Ju; Thiagarajah, Jay R.

2013-01-01

84

Sympathetic support of energy expenditure and sympathetic nervous system activity after gastric bypass surgery  

PubMed Central

Resting energy expenditure (REE) is partially dependent on the sympathetic nervous system as evidenced by the fact REE decreases during systemic beta-adrenergic blockade. It is not known how gastric bypass affects the sympathetically mediated component of REE or muscle sympathetic nerve activity (MSNA). We measured REE before and after beta-blockade in female subjects approximately three years post-gastric bypass surgery and in female obese individuals for comparison. We also measured MSNA in a subset of these subjects. The gastric bypass subjects had no change in REE after systemic beta-blockade, reflecting a lack of sympathetic support of REE, in contrast to obese subjects where REE was reduced by beta-blockade by approximately 5% (P<0.05). The gastric bypass subjects, while still overweight (BMI = 29.3 vs 38.0 kg/m2 for obese subjects, P<0.05), also had significantly lower MSNA compared to obese subjects (10.9 ± 2.3 vs. 21.9 ± 4.1 bursts/min, P<0.05). The reasons for low MSNA and a lack of sympathetically mediated support of REE after gastric bypass are likely multifactorial and may be related to changes in insulin sensitivity, body composition, and leptin, among other factors. These findings may have important consequences for the maintenance of weight loss after gastric bypass. Longitudinal studies are needed to further explore the changes in sympathetic support of REE and if changes in MSNA or tissue responsiveness are related to the sympathetic support of REE.

Curry, Timothy B.; Somaraju, Madhuri; Hines, Casey N.; Groenewald, Cornelius B.; Miles, John M.; Joyner, Michael J.; Charkoudian, Nisha

2012-01-01

85

Electro-acupuncture of Foot YangMing regulates gastric activity possibly through mediation of the dorsal vagal complex.  

PubMed

Acupuncture at some specific acupoints of Foot Yangming can regulate gastric activity. However, its precise mechanism remains unknown. In our study, the effects and mechanism of electro-acupuncture (EA) at Tsusanli (ST 36), Shangchuhsu (ST 37) on the regulation of gastric activity were observed. EA at Tsusanli showed that gastric electric change had a significantly higher frequency and wave amplitude as compared to that of the Shangchuhsu group and other groups. EA at Shangchuhsu demonstrated the change of gastric electric was greater than that of the non-acupoint group and the control group. After bilateral vagotomy, the change of electro gastric graph (EGG) of EA at Tsusanlis was not significant compared to the control group. In the mean time, we have observed the electric discharge of the neurons in NTS and DMV. The frequency of electro-physiological activity in nucleus of solitary tract (NTS) and dorsal motor nucleus of the vagus nerve (DMV) in Tsusanli group and Shangchuhsu group were markedly increased compared with that in other groups. The results have indicated that EA at Tsusanli and Shangchuhsu not only regulate gastric activity, but also activate neurons in NTS and DMV significantly. Our study suggests that the effect of EA at Tsusanli and Shangchuhsu on the gastric activity may partially depend upon integrated nerve pathway and related central neurons in dorsal vagal complex. PMID:17597504

Wang, Jing-Jie; Ming, Qin; Liu, Xiao-Dong; Huang, Yu-Xin; Chen, Liang-Wei; Qiu, Jian-Yong; Duan, Li; Cao, Rong; Rao, Zhi-Ren

2007-01-01

86

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

87

Gene expression and effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer  

PubMed Central

The effects of chemotherapy on gastrointestinal cancer are influenced by the chemotherapeutic sensitivity of the cancer cells. Determining the expression of genes related to chemotherapeutic sensitivity has been used as a molecular method. The aim of the study was to clarify the relationships between the expression of genes related to chemotherapeutic sensitivity and the effects of orally active derivatives of fluoropyrimidine on gastric and colorectal cancer. Forty-five patients who underwent adjuvant chemotherapy containing orally active derivatives of fluoropyrimidine after undergoing curative surgery for gastric or colorectal cancer were enrolled. Twenty-four patients had colorectal cancer and 21 patients had gastric cancer. Total RNA was extracted from formalin-fixed, paraffin-embedded specimens of the resected tumors, and the expression of 11 genes was measured using the RT-PCR method. We then analyzed the relationships between the gene expression and the postoperative relapse rate as well as the relationships between clinicopathological factors and postoperative relapse rate. The median observation period of the subjects was 41 months. Twelve out of the 21 gastric cancer patients (57%) and 11 out of the 24 colorectal cancer patients (46%) relapsed. Although the results of a univariate analysis revealed that expression of none of the evaluated genes was related to relapse in the gastric cancer patients, excision repair cross-complementing gene 1 (ERCC1) overexpression was related to the relapse rate in colorectal cancer patients (p=0.023). When 1.295 was set as the cut-off value for ERCC1 overexpression using the receiver operating characteristic (ROC) curve, 67% of patients with ERCC1 overexpression and 25% of patients without ERCC1 overexpression relapsed. The relapse-free survival rate was lower in the group with ERCC1 overexpression than in the group without ERCC1 overexpression (p=0.046). ERCC1 overexpression appears to be a useful predictor of relapse in colorectal cancer patients receiving adjuvant therapy with regimens including orally active derivatives of fluoropyrimidine.

ARAKAWA, SATOSHI; OZAWA, SOJI; KAWASE, JIN; OSHIMA, HISANORI; NAGATA, HIDETOSHI; ATSUTA, KOJI; UMEMOTO, SHUNJI

2010-01-01

88

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

89

Superior Antitumor Activity of Nanoparticle Albumin-Bound Paclitaxel in Experimental Gastric Cancer  

PubMed Central

Gastric cancer is the second common cause of cancer related death worldwide and lacks highly effective treatment for advanced disease. Nab-paclitaxel is a novel microtubule-inhibitory cytotoxic agent that has not been tested in gastric cancer as of yet. In this study, human gastric cancer cell lines AGS, NCI-N87 and SNU16 were studied. Nab-paclitaxel inhibited cell proliferation with an IC50 of 5 nM in SNU16, 23 nM in AGS and 49 nM in NCI-N87 cells after 72-hour treatment, which was lower than that of oxaliplatin (1.05 ?M to 1.51 ?M) and epirubicin (0.12 ?M to 0.25 ?M). Nab-paclitaxel treatment increased expression of the mitotic-spindle associated phospho-stathmin irrespective of the baseline total or phosphorylated stathmin level, and induced mitotic cell death as confirmed through increased expression of cleaved-PARP and caspase-3. After a two-week nab-paclitaxel, oxaliplatin or epirubicin treatment, the average in vivo local tumor growth inhibition rate was 77, 17.2 and 21.4 percent, respectively (p?=?0.002). Effects of therapy on tumoral proliferative and apoptotic indices corresponded with tumor growth inhibition data, while expression of phospho-stathmin also increased in tissues. There was an increase in median animal survival after nab-paclitaxel treatment (93 days) compared to controls (31 days, p?=?0.0007), oxaliplatin (40 days, p?=?0.0007) or to docetaxel therapy (81 days, p?=?0.0416). The strong antitumor activity of nab-paclitaxel in experimental gastric cancer supports such microtubule-inhibitory strategy for clinical application. Nab-paclitaxel benefits were observed independent from phosphorylated stathmin expression at baseline, putting into question the consideration of nab-paclitaxel use in gastric cancer based on this putative biomarker.

Zhang, Changhua; Awasthi, Niranjan; Schwarz, Margaret A.; Hinz, Stefan; Schwarz, Roderich E.

2013-01-01

90

Superior antitumor activity of nanoparticle albumin-bound paclitaxel in experimental gastric cancer.  

PubMed

Gastric cancer is the second common cause of cancer related death worldwide and lacks highly effective treatment for advanced disease. Nab-paclitaxel is a novel microtubule-inhibitory cytotoxic agent that has not been tested in gastric cancer as of yet. In this study, human gastric cancer cell lines AGS, NCI-N87 and SNU16 were studied. Nab-paclitaxel inhibited cell proliferation with an IC50 of 5 nM in SNU16, 23 nM in AGS and 49 nM in NCI-N87 cells after 72-hour treatment, which was lower than that of oxaliplatin (1.05 ?M to 1.51 ?M) and epirubicin (0.12 ?M to 0.25 ?M). Nab-paclitaxel treatment increased expression of the mitotic-spindle associated phospho-stathmin irrespective of the baseline total or phosphorylated stathmin level, and induced mitotic cell death as confirmed through increased expression of cleaved-PARP and caspase-3. After a two-week nab-paclitaxel, oxaliplatin or epirubicin treatment, the average in vivo local tumor growth inhibition rate was 77, 17.2 and 21.4 percent, respectively (p?=?0.002). Effects of therapy on tumoral proliferative and apoptotic indices corresponded with tumor growth inhibition data, while expression of phospho-stathmin also increased in tissues. There was an increase in median animal survival after nab-paclitaxel treatment (93 days) compared to controls (31 days, p?=?0.0007), oxaliplatin (40 days, p?=?0.0007) or to docetaxel therapy (81 days, p?=?0.0416). The strong antitumor activity of nab-paclitaxel in experimental gastric cancer supports such microtubule-inhibitory strategy for clinical application. Nab-paclitaxel benefits were observed independent from phosphorylated stathmin expression at baseline, putting into question the consideration of nab-paclitaxel use in gastric cancer based on this putative biomarker. PMID:23460921

Zhang, Changhua; Awasthi, Niranjan; Schwarz, Margaret A; Hinz, Stefan; Schwarz, Roderich E

2013-02-27

91

Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control Study  

Microsoft Academic Search

BackgroundCagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer.MethodsIn the discovery phase, a total of 580 SNPs within +\\/?5 kbp of 30 candidate genes were

Jae Jeong Yang; Lisa Y. Cho; Seung Hyun Ma; Kwang-Pil Ko; Aesun Shin; Bo Youl Choi; Dong Soo Han; Kyu Sang Song; Yong Sung Kim; Soung-Hoon Chang; Hai-Rim Shin; Daehee Kang; Keun-Young Yoo; Sue K. Park

2011-01-01

92

Disruption of glial function regulates the effects of electro-acupuncture at Tsusanli on gastric activity in rats.  

PubMed

According to recent evidence, acupuncture at Tsusanli (ST 36) can regulate gastric activity. And this regulation mainly depends upon neural basis or structure and may probably relate to the central neurons in the dorsal vagal complex. However, whether the glias of the dorsal vagal complex participate in the regulation of gastric activity, when electro-acupuncture (EA) at Tsusanli, still remains to be interpreted. In this study, we observed the effect of EA at Tsusanli (ST 36) on regulation of gastric activity. Propentofylline (PPF), a glial metabolic inhibitor, was used to inhibit the function of glial cells. EA at Tsusanli showed that the expressions of glial fibrillary acidic protein (GFAP) and OX42 increased significantly compared to that of the control group, and gastric electric change was obvious, with significantly higher frequency and wave amplitude compared to the control group. The expressions of GFAP and OX42 were decreased markedly when pretreated with PPF group than without PPF pretreatment group. Compared to the Tsusanli group and the control group, the changes of electro gastric graph (EGG) were significantly decreased in PPF pretreatment group. On the other hand, we observed the changes of spontaneous electro-activity of the DVC (dorsal vagal complex) in our previous experiment. The results indicated that EA at Tsusanli could activate glial cells in the dorsal vagal complex and regulate gastric activity. PPF blocked the function of glia, thus the effect of EA at Tsusanli on gastric activity was weakened. Our study suggested that this electro-acupuncture regulation of gastric activity was possibly related with glia of the dorsal vagal complex. PMID:19655404

Wang, Sheng-Zhi; Liu, Xiao-Dong; Huang, Yu-Xin; Ma, Qing-Jiu; Wang, Jing-Jie

2009-01-01

93

Integrative network analysis reveals active microRNAs and their functions in gastric cancer  

PubMed Central

Background MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs. Results We integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate. Conclusions This study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.

2011-01-01

94

Effects of Octreotide and Erythromycin on Gastric Myoelectrical and Motor Activities in Patients with Gastroparesis  

Microsoft Academic Search

Simultaneous recordings of gastric manometry andmyoelectrical activity were made in 10 patients withgastroparesis. Intravenous erythromycin (100 mg) wasadministered in the fasting state for a period of 30 min. Subcutaneous injection of octreotide(100 µg) was administered before one of the fouridentical test meals. It was found that octreotidesignificantly decreased the antral motility index(30-min fasting: 4.51 ± 1.04 vs 1.75 ±0.97, P

J. D. Z. Chen; Z. Y. Lin; M. C. EDMUNDS III; R. W. Mccallum

1998-01-01

95

Wnt\\/beta-Catenin Signaling Enhances Cyclooxygenase2 (COX2) Transcriptional Activity in Gastric Cancer Cells  

Microsoft Academic Search

BackgroundIncreased 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 FindingsHere we

Felipe Nuńez; Soraya Bravo; Fernando Cruzat; Martín Montecino; Giancarlo V. de Ferrari; Moray Campbell

2011-01-01

96

Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer  

Microsoft Academic Search

BACKGROUND: The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic

Da-zhi Xu; Qi-rong Geng; Ying Tian; Mu-yan Cai; Xin-juan Fang; You-qing Zhan; Zhi-wei Zhou; Wei Li; Ying-bo Chen; Xiao-wei Sun; Yuan-xiang Guan; Yuan-fang Li; Tong-yu Lin

2010-01-01

97

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

98

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.  

PubMed

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa. PMID:11679970

Kawanaka, H; Tomikawa, M; Jones, M K; Szabo, I L; Pai, R; Baatar, D; Tsugawa, K; Sugimachi, K; Sarfeh, I J; Tarnawski, A S

2001-11-01

99

Gastric expression of plasminogen activator inhibitor (PAI)-1 is associated with hyperphagia and obesity in mice.  

PubMed

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. PMID:23254194

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

2012-12-18

100

Curcumin suppresses gastric NF-?B activation and macromolecular leakage in Helicobacter pylori-infected rats  

PubMed Central

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

Sintara, Kawiya; Thong-Ngam, Duangporn; Patumraj, Suthiluk; Klaikeaw, Naruemon; Chatsuwan, Tanittha

2010-01-01

101

The effect of rebamipide on gastric xanthine oxidase activity and type conversion in ethanol-treated rats  

Microsoft Academic Search

Rebamipide, a novel antipeptic ulcer drug, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4-yl]-propionic acid, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intraperitoneal administration of rebamipide at 60 mg\\/kg body weight reduced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of rebamipide

Keun Huh; Uk S. Shin; Sang H. Lee

1996-01-01

102

Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men  

Microsoft Academic Search

OBJECTIVE:The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity.METHODS:Thirteen older (65–84 yr) and 13 young (18–32 yr) healthy men received isovolumetric, intraduodenal (ID) infusions of

Caroline G. MacIntosh; Michael Horowitz; Marc A. M. T. Verhagen; Andre J. P. M. Smout; Judith Wishart; Howard Morris; Elizabeth Goble; John E. Morley; Ian M. Chapman

2001-01-01

103

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-? via the PI 3-kinase–Akt signaling pathway  

Microsoft Academic Search

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-? in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2)

Hirofumi Kawanaka; Michael K. Jones; Imre L. Szabo; Dolgor Baatar; Rama Pai; Kouji Tsugawa; Keizo Sugimachi; I. James Sarfeh; Andrzej S. Tarnawski

2002-01-01

104

Separation of gastric electrical control activity from simultaneous MGG/EGG recordings using independent component analysis.  

PubMed

Spatiotemporal parameters of gastric electrical control activity such as its amplitude, direction and propagation velocity are physiological parameters of distinctive clinical interest due to their potential use for differentiating between the healthy and diseased states of the human stomach. Whereas their time evolution is relatively well behaved in the case of healthy subjects, significant deviations from normal have been observed in patients suffering from a number of gastric diseases such as gastroparesis and gastropathy. For this reason, monitoring ECA parameters noninvasively may offer a useful test for the presence of such diseases whose diagnosis remains problematic. Here, we describe a method for computing ECA direction and orientation from simultaneous, noninvasive magnetogastrographic (MGG) and electrogastrographic (EGG) recordings. We demonstrate how independent component analysis and standard frequency analysis methods can be used to predict the locations and orientations of gastric current dipoles from MGG/EGG data. We compare our MGG-based dipole parameters to analogous ones obtained from simultaneous EGG recordings within the experimental framework of a human model. We find that magnetic recordings are superior in their ability to portray the underlying physiology of the stomach. PMID:17946157

Irimia, Andrie; Gallucci, Michael R; Richards, William O; Bradshaw, L Alan

2006-01-01

105

GESTATIONAL AGE AT BIRTH AND RISK OF GASTRIC ACID-RELATED DISORDERS IN YOUNG ADULTHOOD  

PubMed Central

Purpose Preterm birth is associated with gastric acid-related disorders in infancy, but no studies have examined this association beyond early childhood. We used antisecretory medication data to explore whether preterm birth is associated with gastric acid-related disorders in young adulthood. Methods National cohort study of 626,811 individuals born in Sweden in 1973–1979, followed up for antisecretory (proton pump inhibitor and H2-receptor antagonist) medication prescriptions from all outpatient and inpatient pharmacies nationwide in 2005–2009 (ages 25.5–37.0 years). We excluded individuals with congenital anomalies, and examined potential confounding by other comorbidities identified on the basis of oral anti-inflammatory or corticosteroid medication prescription. Results Gestational age at birth was inversely associated with antisecretory medication prescription in young adulthood. Adjusted odds ratios for ?1 antisecretory medication prescription/year were 3.38 (95% CI, 1.73–6.62) for individuals born at 22–27 weeks, 1.38 (95% CI, 1.19–1.60) for those born at 28–34 weeks, and 1.19 (95% CI, 1.06–1.32) for those born at 35–36 weeks, relative to those born full-term (37–42 weeks). Exclusion of individuals who were prescribed oral anti-inflammatory or corticosteroid medications (?1/year) had little effect on these results. Conclusion These findings suggest that low gestational age at birth may be independently associated with an increased risk of gastric acid-related disorders in young adulthood.

Crump, Casey; Winkleby, Marilyn A.; Sundquist, Jan; Sundquist, Kristina

2012-01-01

106

Premalignant lesions in gastric cancer  

Microsoft Academic Search

Despite a plateau in incidence, gastric cancer is one of the most common cancers worldwide and causes considerable morbidity\\u000a and mortality. Premalignant gastric lesions are well known risk factors for the development of intestinal-type gastric adenocarcinomas.\\u000a In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages

Kazuo Yashima; Shuji Sasaki; Masaharu Koda; Koichiro Kawaguchi; Kenichi Harada; Yoshikazu Murawaki

2010-01-01

107

Physical Activity Predicts Weight Loss Following Gastric Bypass Surgery: Findings from a Support Group Survey  

Microsoft Academic Search

Background  Patient adherence to recommended eating and physical activity behaviors is considered important to weight loss outcomes following\\u000a gastric bypass surgery, but there has been little systematic research in this area to investigate behavioral predictors of\\u000a weight loss.\\u000a \\u000a \\u000a \\u000a Method  We developed a measure of postsurgical behaviors, the bariatric surgery self-management questionnaire (BSSQ). A survey was\\u000a conducted of 200 patients attending postsurgical support

Garry Welch; Cheryl Wesolowski; Bernadette Piepul; Jay Kuhn; John Romanelli; Jane Garb

2008-01-01

108

Physical Activity in Gastric Bypass Patients: Associations with Weight Loss and Psychosocial Functioning at 12Month Follow-Up  

Microsoft Academic Search

Background  This study examined self-reported frequency and intensity of physical activity in gastric bypass patients, and the relationship\\u000a between physical activity and weight loss and psychosocial outcomes during 12-month postoperative follow-up.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Participants were 131 obese patients who underwent gastric bypass surgery and completed psychometrically established measures\\u000a assessing physical activity, depression, and physical and mental health preoperatively and at a 12-month follow-up

Patricia H. Rosenberger; Kathryn Elizabeth Henderson; Marney A. White; Robin M. Masheb; Carlos M. Grilo

109

Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin  

Microsoft Academic Search

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory\\u000a drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole\\u000a against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric\\u000a gavage were 1% methocel as vehicle; esomeprazole 10, 30, or

O. Pastoris; M. Verri; F. Boschi; O. Kastsiuchenka; B. Balestra; F. Pace; M. Tonini; G. Natale

2008-01-01

110

Salovum Egg Yolk Containing Antisecretory Factor As an Adjunct Therapy in Severe Cholera in Adult Males: A Pilot Study  

PubMed Central

Cholera involves stimulation of intestinal secretory process in response to cholera toxin leading to profuse watery diarrhoea that might cause death due to dehydration unless timely rehydration therapy is initiated. Efforts to identify and test potential antisecretory agents are ongoing. Antisecretory factor (AF) is a naturally-occurring protein produced in the human secretory organs, including the intestine, with antisectory properties demonstrated in animal and human models of secretory diarrhoea. Salovum egg yolk powder contains proteins with antisecretory properties in a much higher (500 times) concentration than that of normal hen eggs. This is achieved by feeding hens with specially-processed cereals, capable of inducing proteins with antisecretory properties in the yolk. The aim of the study was to examine the effect of Salovum egg yolk powder containing AF in the treatment of adult cholera patients. In an open, randomized controlled trial (pilot study), 40 adult male patients with severe cholera were studied: 20 received standard treatment (oral rehydration solution, antibiotic, and usual hospital diet) plus Salovum egg yolk powder (study group) and 20 received standard treatment alone (control group). All the patients received tablet doxycycline (300 mg) once immediately after randomization. Written informed consent was obtained from each subject before enrollment. The main outcome measures were stool weight and duration of diarrhoea. The demographic and baseline clinical characteristics of the study patients were comparable between the groups. No significant differences were found in the mean stool weight, g/kg of body-weight during the first 24 hours [study vs control group, mean±standard deviation (SD), 218±119 vs 195±136], second 24 hours (mean±SD, 23±39 vs 22±34), and cumulative up to 72 hours (mean±SD, 245±152 vs 218±169). The duration (hours) of diarrhoea after admission in the hospital was also similar in both the groups (mean±SD, 33±14 vs 32±10). No adverse effect was observed. Salovum egg powder containing AF as an adjunct therapy in the treatment of severe cholera could not demonstrate any beneficial effect. Further studies with higher doses of Salovum egg yolk powder might be considered in future to establish its antisecretory effect.

Ashraf, Hasan; Olesen, Maryam; Salam, Mohammed A.; Gyr, Niklaus; Meier, Remy

2011-01-01

111

Psychosocial and physical activity changes after gastric restrictive procedures for morbid obesity.  

PubMed

Gastric restrictive procedures for morbid obesity are frequently performed to reduce problems arising from the physical limitations and social isolation of massive obesity. Numerous reports have described changes in weight after gastric restrictive operations, yet few studies have documented changes in the secondary effects of obesity. This report deals with changes in psychosocial status and physical activity occurring in 240 patients who remained in the study 3 years after surgery. These patients were members of a group of 310 patients who were entered into a prospective randomized trial to assess the relative benefits of three forms of gastric restrictive procedure. Prior to operation, and at yearly intervals after operation, the physical activities and psychosocial status of each patient was assessed by a standardized semi-structured interview. At the time of the three-year interview the median weight loss for these patients was 29.5 kg which represents 53% of excess weight lost. This weight loss was associated with a marked reduction in the amount of food eaten. There was a significant increase in the number of patients smoking more than 20 cigarettes a day and a mild increase in alcohol intake. There were significant improvements in the level of self-image and state of happiness. The social lives and sex lives of the majority of patients were improved and a significantly greater number of patients reported being in a stable emotional relationship at 3 years after operation than did so pre-operatively. There was a marked increase in the number of patients in full-time or part-time employment from 38% prior to surgery to 60% at 3 years after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2206119

Hawke, A; O'Brien, P; Watts, J M; Hall, J; Dunstan, R E; Walsh, J F; Slavotinek, A H; Elmslie, R G

1990-10-01

112

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

113

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

2012-07-11

114

Ethanol Injury Triggers Activation of Adrenomedullin and Its Receptor Genes in Gastric Mucosa  

Microsoft Academic Search

Adrenomedullin (AM) is a potent vasodilatorypeptide, which is present in the stomach. However, itsprecise function in the gastric mucosa is unknown. Theexpression and localization of AM and its receptor in gastric mucosa injured by ethanol also havenot been explored, forming the basis for this study.Gastric samples of rats were obtained at 0 and 8 hr and1, 2, and 4 days

Hongtao Wang; Morimasa Tomikawa; Michael K. Jones; I. James Sarfeh; Andrzej S. Tarnawski

1999-01-01

115

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

116

Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of N-[3-(3-(1-piperidinylmethyl) phenoxy)propyl]-hydroxyacetamide 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex (MX1)-MX1.  

PubMed

MX1 (N-[3-(3-(1-piperidinylmethyl)phenoxy)propyl]-hydroxyacetamide+ ++ 2-hydroxypropane-1,2,3-tricarboxylate bismuth (3+) complex) is a novel salt of the active metabolite of H2-antagonist roxatidine with a complex of bismuth with citric acid. In a model of ethanol-induced ulcers in male Wistar rats, both roxatidine and the bismuth salt reduced the number and the total length of lesions. Comparison of roxatidine and MX1 at equimolar doses of 160 mumol kg-1 showed a more potent cytoprotective effect of MX1. The potency of anti-secretory and antiacidic effects of MX1 was more than twice that of roxatidine on histamine-stimulated secretion in female Wistar pylorus-ligated rats. Microbiological tests with the reference bismuth preparation De-Nol showed prominent anti-Helicobacter properties of MX1 in-vitro. Both test compounds had similar range of MICs to Helicobacter pylori, from 4 to 64 microgram bismuth mL-1. The cytoprotective, antisecretory, anti-acidic and anti-Helicobacter properties of the new agent MX1 warrant further more extensive pharmacological and clinical trials. PMID:8737057

Ivanov, C; Petkov, O; Petrov, P; Taskov, M; Athanassova, R; Tsvetkova, E; Kotsev, V; Lyutakov, G; Nikolov, G; Savov, E

1996-03-01

117

Activated CD8+ T cells contribute to clearance of gastric Cryptosporidium muris infections.  

PubMed

The role of CD4+ and CD8+ T lymphocytes in the development of a protective immune response against Cryptosporidium muris infection was studied by the reconstitution of severe combined immunodeficient (SCID) mice with well-defined populations of either naive or immune CD8+ or CD4+ T lymphocytes. Adoptive transfer of both naive and immune CD4+ T lymphocyte subpopulations protects SCID mice against cryptosporidiosis. Moreover, a significant biological impact of activated CD8+ T cells against gastric cryptosporidiosis was observed. The significant difference in the course and intensity of the infection in reconstituted SCID mice was found to be dependent on the protective function of both the CD4+ and CD8+ T-cell populations transferred. While SCID mice reconstituted with either immune or naive CD4+ or immune CD8+ T-cell subpopulations resolved the infection within 29, 37 and 51 days post-infection, respectively, those reconstituted with naive CD8+ T cells suffered from chronic infection similar to control SCID mice. Reconstitution with CD4+ T cells resulted in suppression of oocyst excretion and shortening of patent period in comparison with SCID mice reconstituted with CD8+ T cells. Thus, although CD4+ T cells are considered important in protective immunity, our results are the first to demonstrate the involvement of activated CD8+ T lymphocytes in the protection of mice against gastric cryptosporidiosis. PMID:21204850

Kvá?, M; Kodádková, A; Sak, B; Kv?to?ová, D; Jalovecká, M; Rost, M; Salát, J

2011-04-01

118

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

119

Activation of STAT3 in Human Gastric Cancer Cells via Interleukin (IL)-6-Type Cytokine Signaling Correlates with Clinical Implications  

PubMed Central

Background The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays important roles in oncogenesis, angiogenesis, immunity, and tumor cell invasion. In the present study, we investigated the association of interleukin (IL)-6/STAT3 signaling pathway with T lymphocytes and clinical implication in patients with gastric cancer. Methods Seventy one patients who underwent gastrectomy due to gastric adenocarcinoma were studied. Blood samples were collected before and after surgical gastrectomy to quantify the levels of IL-6, IL-10 and VEGF using an enzyme-linked immunosorbent assay, as well as T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and natural killer (NK) cells by a flow cytometry. Furthermore, the expression of IL-6, survivin, STAT3, STAT3 phosphorylation (p-STAT3), and VEGF were determined in human gastric cancer and adjacent normal mucosa through Western blot and immunohistochemistry. Results Postoperative levels of IL-6, IL-10 and VEGF in serum were significantly lower than preoperative levels. Percentages of T-cell subsets and NK cells in blood were significantly increased after postoperative-week 1 as compared to preoperative group, which was further augmented at 1 month after gastrectomy. In addition, the expression of IL-6, survivin, STAT3, p-STAT3, and VEGF were increased in human gastric cancer tissues as compared to adjacent normal mucosa. Their expression was associated with TNM stage of gastric cancer. The level of STAT3 activation in clinical samples was correlated with IL-6 expression. All gastric tumor samples, which expressed p-STAT3, also expressed IL-6 with weak expression detected in adjacent normal mucosa. Conclusion Increased IL-6-induced activation of STAT3 was observed in neoplastic gastric tissue, which positively correlated with tumor progression. Moreover, IL-6 and STAT3 downstream signals such as IL-10 and VEGF were reduced in patients after removal of gastric cancer as compared to pre-operation. Therefore, inhibition of the IL-6/STAT3 signaling pathway may provide a new therapeutic strategy against gastric cancer.

Xu, Aman; Meng, Xiangning; Gao, Shile; Qi, Yijun; Zhu, Liang; Li, Tuanjie; Li, Weiping; Dong, Liuyi

2013-01-01

120

Portal hypertensive gastric mucosa has reduced activation of MAP kinase (ERK2) in response to alcohol injury: a key to impaired healing?  

PubMed

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Because our previous study showed that ulcer-induced activation of mitogen-activated protein (MAP) kinase (ERK) plays a pivotal role in gastric mucosal healing, we investigated whether ERK activation is altered in PHT gastric mucosa following alcohol injury. We studied ERK2 phosphorylation and activity and expression of MAP kinase phosphatase-1 (MKP-1) in gastric mucosa of PHT and sham-operated (SO) normal rats both at baseline and following alcohol injury. In SO gastric mucosa, ERK2 phosphorylation and activity were significantly increased time-dependently following alcohol injury: by 221% and 137%, respectively at 24 h vs. baseline. In contrast, in PHT gastric mucosa following alcohol injury, neither ERK2 phosphorylation nor activity was increased versus baseline. In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats. Because ERK2 is crucial for mucosal healing, reduced ERK2 activation resulting from the overexpression of MKP-1 might be the basis for the impaired mucosal healing in PHT gastric mucosa. PMID:11259371

Kawanaka, H; Tomikawa, M; Jones, M K; Pai, R; Szabo, I L; Sugimachi, K; Sarfeh, I J; Tarnawski, A S

2001-01-05

121

Detection of active bleeding from gastric antral vascular ectasia by capsule endoscopy.  

PubMed

Gastric antral vascular ectasia (GAVE) has been recognized as one of the important causes of occult and obscure gastrointestinal bleeding. The diagnosis is typically made based on the characteristic endoscopic features, including longitudinal row of flat, reddish stripes radiating from the pylorus into the antrum that resemble the stripes on a watermelon. These appearances, however, can easily be misinterpreted as moderate to severe gastritis. Although it is believed that capsule endoscopy (CE) is not helpful for the study of the stomach with its large lumen, GAVE can be more likely to be detected at CE rather than conventional endoscopy. CE can be regarded as "physiologic" endoscopy, without the need for gastric inflation and subsequent compression of the vasculature. The blood flow of the ecstatic vessels may be diminished in an inflated stomach. Therefore, GAVE may be prominent in CE. We herein describe a case of active bleeding from GAVE detected by CE and would like to emphasize a possibility that CE can improve diagnostic yields for GAVE. PMID:23515703

Ohira, Tetsuya; Hokama, Akira; Kinjo, Nagisa; Nakamoto, Manabu; Kobashigawa, Chiharu; Kise, Yuya; Yamashiro, Satoshi; Kinjo, Fukunori; Kuniyoshi, Yukio; Fujita, Jiro

2013-03-16

122

The Role of Peroxisome Proliferator-Activated Receptors in the Esophageal, Gastric, and Colorectal Cancer  

PubMed Central

Tumors of the gastrointestinal tract are among the most frequent human malignancies and account for approximately 30% of cancer-related deaths worldwide. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control diverse cellular functions such as proliferation, differentiation, and cell death. Owing to their involvement in so many processes, they play crucial roles also in the development and physiology of the gastrointestinal tract. Consistently, PPARs deregulation has been implicated in several pathophysiological conditions, including chronic inflammation and cancer development. This paper summarizes the current knowledge on the role that the various PPAR isoforms play in the pathogenesis of the esophageal, gastric, and intestinal cancer. Elucidation of the molecular mechanisms underlying PPARs' signaling pathways will provide insights into their possible use as predictive biomarkers in the initial stages of the process. In addition, this understanding will provide the basis for new molecular targets in cancer therapy and chemoprevention.

Fucci, Alessandra; Colangelo, Tommaso; Votino, Carolina; Pancione, Massimo; Sabatino, Lina; Colantuoni, Vittorio

2012-01-01

123

3,3'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway.  

PubMed

Recent studies have revealed that 3,3-diindolylmethane (DIM) has antitumor effects in both in vivo and in vitro tumor models. However, the biological function of DIM in human gastric cancer cells is unknown. Genetic and biological studies have confirmed the importance of the novel Hippo tumor-suppressor pathway in regulating cell proliferation, apoptosis, organ size and tumorigenesis in mammals. Thus, the purpose of this study was to investigate the cytotoxic effects of DIM in human gastric cancer cells and to elucidate whether DIM induces cell death by activating the Hippo signaling pathway. Two human gastric cancer cell lines (SNU-1 and SNU-484) were used to investigate the DIM response. DIM significantly inhibited the proliferation of human gastric cancer cells in a dose-dependent manner. The percentage of G1 phase cells increased 24 h following DIM treatment. DIM reduced CDK2, CDK4, CDK6 and cyclin D1 protein levels, while increasing p53 protein levels. DIM induced the levels of cleaved poly(ADP-ribose) polymerase, cleaved-caspase-9, and diminished pro-caspase-3 protein production. In addition, DIM increased pLATS1, Mob1, pMob1, pYAP and Ras association domain family 1 (RASSF1) protein levels and reduced Yap protein production levels. DIM stimulated the binding of RASSF1 with the Mst1/2-LATS1-Mob1 complex, promoting an active Hippo signaling pathway and favoring YAP phosphorylation (pYAP) that inactivates cell proliferation. Furthermore, DIM inhibited the growth of human gastric tumors in a xenograft mouse model. These results indicate that DIM suppresses the growth of gastric cancer cells by activating the Hippo signaling pathway. PMID:24008339

Li, Xiu Juan; Park, Eun Sung; Park, Man Hee; Kim, Soo Mi

2013-09-04

124

Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A2A adenosine receptor in rats  

PubMed Central

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin induce gastric mucosal lesions in part by the activation of inflammatory cells and the production of proinflammatory cytokines. The activation of adenosine A2A receptors inhibits inflammation by increasing cyclic AMP in leukocytes and reducing both the production of various proinflammatory cytokines and neutrophil chemotaxis. The aim of present study was to determine whether administration of an orally active adenosine A2A receptor agonist (4-[3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-piperidine-1-carboxylic acid methyl ester; ATL-313) ameliorated indomethacin-induced gastric mucosal lesions in rats. Methods Gastric lesions were produced by oral gavage of indomethacin (30 mg/kg). ATL-313 (1–10 ?g/kg) was given orally just before the indomethacin administration. Results The ulcer index induced by indomethacin was significantly (>50%) reduced by pretreatment with ATL-313 and this effect was blocked completely by the addition of equimolar ZM241385, a selective A2A receptor antagonist. The gastric content of myeloperoxidase (MPO) and proinflammatory cytokines was significantly reduced by 10 ?g/kg ATL-313, but gastric mucosal prostaglandin 2 (PGE2) was not affected. Conclusion We conclude that ATL-313 does not inhibit the mucosal damaging effect of indomethacin, but it does block secondary injury due to stomach inflammation. A2A agonists may represent a class of new therapeutic drugs for NSAID-induced gastric ulcers.

Koizumi, Shigeto; Otaka, Michiro; Jin, Mario; Linden, Joel; Watanabe, Sumio; Ohnishi, Hirohide

2010-01-01

125

The effect of general anaesthesia on gastric myoelectric activity in experimental pigs  

PubMed Central

Background Surface electrogastrography (EGG) is a non-invasive method for clinical assessment of gastric myoelectrical activity. Different forms of general anaesthesia might have various effects on porcine EGG. The aim of this study was to evaluate the impact of different anaesthetic agents on EGG in experimental pigs. Methods Four 15-minute EGG intervals were recorded and analysed. A baseline EGG recording was started 20?minutes after intramuscular injection of ketamine and azaperone (periods A and B). Four different regimens of general anaesthesia followed immediately after the baseline EGG (5 pigs in each experimental group): thiopental, isoflurane, nitrous oxide and isoflurane plus nitrous oxide. EGG recordings followed for the next 30?minutes under general anaesthesia (periods C and D). The dominant frequencies of slow waves were compared between the baseline intervals A and B and periods C and D under general anaesthesia. Results The mean dominant frequency was within the normal range (2.3 – 3.5?cycles per minute) in all animals in all regimens. Thiopental general anaesthesia did not influence any change of the dominant frequency of slow waves. Nitrous oxide general anaesthesia increased the dominant frequency of slow waves in a statistically significant manner (baseline: 2.93?±?0.53 and 3.01?±?0.53; under general anaesthesia: 3.25?±?0.34 and 3.29?±?0.38?cycles per minute; p?gastric myoelectric activity assessed by the dominant frequency of slow waves during EGG remained within the normal range although some of them achieved statistical significance. Thus all tested agents used for general anaesthesia can be recommended in preclinical studies with porcine models focused on gastric myoelectric activity without any risk of compromising the results. Thiopental seems to be the most suitable as it did not cause any changes at all.

2013-01-01

126

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: Potential therapeutic implications  

Microsoft Academic Search

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against

Hirofumi Kawanaka; Morimasa Tomikawa; Michael K. Jones; Imre L. Szabo; Rama Pai; Dolgor Baatar; Kouji Tsugawa; Keizo Sugimachi; I. James Sarfeh; Andrzej S. Tarnawski

2001-01-01

127

Regulation of Interleukin-6 Promoter Activation in Gastric Epithelial Cells Infected with Helicobacter pylori  

PubMed Central

The regulation of Helicobacter pylori induced interleukin (IL)-6 in the gastric epithelium remains unclear. Primary gastric epithelial cells and MKN28 cells were cocultured with H. pylori and its isogenic cag pathogenicity island (PAI) mutant and/or oipA mutants. H. pylori infection-induced IL-6 mRNA expression and IL-6 protein production, which was further enhanced by the cag PAI and OipA. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that full IL-6 transcription required binding sites for nuclear factor-?B (NF-?B), cAMP response element (CRE), CCAAT/enhancer binding protein (C/EBP), and activator protein (AP)-1. The cag PAI and OipA were involved in binding to NF-?B, AP-1, CRE, and C/EBP sites. The cag PAI activated the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) pathways; OipA activated the p38 pathway. Transfection of dominant negative G-protein confirmed roles for Raf, Rac1, and RhoA in IL-6 induction. Overall, the cag PAI-related IL-6 signal transduction pathway involved the Ras/Raf/MEK1/2/ERK/AP-1/CRE pathway and the JNK/AP-1/CRE pathway; the OipA-related pathway is p38/AP-1/CRE and both the cag PAI and OipA appear to be involved in the RhoA/Rac1/NF-?B pathway. Combination of different pathways by the cag PAI and OipA will lead to the maximum IL-6 induction.

Lu, Hong; Wu, Jeng Yih; Kudo, Takahiko; Ohno, Tomoyuki; Graham, David Y.; Yamaoka, Yoshio

2005-01-01

128

Prognostic role of telomerase activity in gastric adenocarcinoma: A meta-analysis  

PubMed Central

Activation of telomerase is involved in carcinogenesis in most types of cancers. However, the prognostic value of telomerase activity (TA) in patients with gastric carcinoma (GC) remains controversial. We conducted a meta-analysis to assess the relationship between TA and the clinical outcome of GC. A meta-analysis of 18 studies (886 patients) was performed to evaluate the association between TA and metastasis-related parameters in GC patients by searching databases, including PubMed, MEDLINE, EMBASE, Web of Science databases, Cochrane Library and the Chinese Biomedical Literature database (CBM) (last search updated in October 2011). We used the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between TA and metastasis of GC. Our analysis results indicated that high telomerase activity expression tended to be associated with the presence of lymph node metastasis (866 patients) (OR=2.03, 95% CI 1.21–3.39, p=0.007), the depth of invasion (886 patients) (OR=1.87, 95% CI 1.30–2.70, p=0.0007), distant metastasis (407 patients) (OR=2.71, 95% CI 1.59–4.63, p=0.0002), tumor size (466 patients) (OR=2.14, 95% CI 1.31–3.50, p=0.002) and TNM stage (711 patients) (OR=2.39, 95% CI 1.30–4.41, p=0.005). However, high TA expression was not associated with the presence of histologic differentiation (791 patients) (OR=1.51, 95% CI 0.73–3.11, p=0.26). In conclusion, telomerase overexpression not only plays a key role in primary initiation, but also promotes invasion and metastatic progression of GC. These findings raise the possibility of using TA to screen for the prognosis of gastric cancer.

LU, MU-HAN; DENG, JIA-QI; CAO, YA-LING; FANG, DIAN-CHUN; ZHANG, YAO; YANG, SHI-MING

2012-01-01

129

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

Microsoft Academic Search

Summary  In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output,\\u000a but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays\\u000a a role in the regulation of gastric acid.\\u000a \\u000a \\u000a \\u000a Introduction  Gastric acid secretion is a complex process regulated by neuronal and hormonal

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

2009-01-01

130

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

2013-05-25

131

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

PubMed

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-G(R) 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-G(R) 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. PMID:21193525

Nřrsett, 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; Varro, Andrea

2010-12-30

132

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

133

Nuclear translocation of small G protein RhoA via active transportation in gastric cancer cells.  

PubMed

Recent studies have shown the localization of RhoA in the cell nucleus, in addition to its cellular distribution in the cytosol and cell membrane. Our previous results that a high amount of RhoA was detected in gastric cancer cell nucleus and application of anticancer drug Taxol could reduce RhoA nuclear localization, suggest a relationship between nuclear translocation of RhoA and tumor progression. However, the mechanism and biological function of RhoA nuclear translocation remain unclear. The aim of the present study was to explore the mole-cular mechanism(s) for RhoA protein entering the nucleus in the human gastric cancer cell line AGS. Using immunofluorescence microscopy we observed not only a partial colocalization of RhoA with importin ?, mainly surrounding and on the nuclear membrane, but also an intensive colocalization of RhoA with NF-?B P50 in both cytoplasm and nucleus, particularly in the cell nucleoli. A strong association between RhoA and importin ? as well as RhoA and NF-?B P50 was revealed by co-immunoprecipitation and western blotting. Moreover, AGS cells treated with the nuclear export inhibitor, leptomycin B (LMB), showed an increase of RhoA protein amount in the nucleus, indicating an active transport process for nuclear export of RhoA. Taken together, our results suggest that nuclear translocation of RhoA in AGS cells is via active transportation, a process through importin ? in a NF-?B-dependent manner. PMID:23900609

Xu, Jin; Li, Yueying; Yang, Xiaoming; Chen, Yongchang; Chen, Min

2013-07-25

134

Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed gastric emptying in a canine model of diabetic gastroparesis.  

PubMed

1. The aim of the present study was to evaluate the effects of mitemcinal (GM-611), an orally active motilin receptor agonist, on delayed gastric emptying in a canine model of diabetic gastroparesis and to compare these effects with those of cisapride. 2. Moderate hyperglycaemia was induced by a single intravenous injection of a mixture of streptozotocin (30 mg/kg) and alloxan (50 mg/kg). Dogs that maintained moderate hyperglycaemia (fasting plasma glucose 200-300 mg/dL) without insulin treatment were selected and gastric emptying in these dogs was determined by the paracetamol method. 3. One year after the onset of diabetes, there was no difference in the gastric emptying of normal and diabetic dogs. However, after 5 years, the diabetic dogs showed delayed gastric emptying. The motor nerve conduction velocity of the tibial nerve was significantly lower in diabetic dogs compared with normal dogs at both time points. 4. Histopathological examination at the end of the study showed that there were fewer nerve fibres in both dorsal vagal and tibial nerves of diabetic dogs compared with normal dogs. The onset of delayed gastric emptying is thought to have occurred gradually, in parallel with abnormal autonomic nerve function induced by the long period of moderate hyperglycaemia. 5. Oral administration of mitemcinal (0.125, 0.25 or 0.5 mg/kg) dose-dependently accelerated delayed gastric emptying, significant at 0.5 mg/kg, in diabetic dogs, whereas cisapride (1, 3 or 10 mg/kg) had no significant effect. These results add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis. PMID:18346169

Onoma, Mitsu; Ozaki, Ken-ichi; Yogo, Kenji; Monnai, Makoto; Muramatsu, Hiroyasu; Kamei, Kenshi; Kawabe, Yoshiki; Hayashi, Shuji; Shiga, Toshihiko; Matsuo, Saori; Suzuki, Masami; Itoh, Zen; Omura, Satoshi; Takanashi, Hisanori

2008-03-13

135

Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-? and COX-2-dependent signals  

PubMed Central

Background and purpose: Peroxisome proliferator-activated receptor-? (PPAR-?), COX-2 and 15-lipoxygenase (LOX)-1 have been shown to be involved in tumour growth. However, the roles of PPAR-?, COX-2 or 15-LOX-1 in gastric tumourigenesis remain unclear. Here, we investigate the role of 15-LOX-1 induction by honokiol, a small-molecular weight natural product, in PPAR-? and COX-2 signalling during gastric tumourigenesis. Experimental approach: Human gastric cancer cell lines (AGS, MKN45, N87 and SCM-1) were cultured with or without honokiol. Gene and protein expressions were analysed by RT–PCR and Western blotting respectively. Small interfering RNAs (siRNAs) for COX-2, PPAR-? and 15-LOX-1 were used to interfere with the expressions of these genes. A xenograft gastric tumour model in mouse was used for in vivo study. Key results: PPAR-? and COX-2 proteins were highly expressed in gastric cancer cells. Inhibitors, or siRNA for COX-2 or PPAR-?, significantly decreased cell viability. Honokiol markedly inhibited PPAR-? and COX-2 expressions in gastric cancer cells and tumours of xenograft mice, and induced apoptosis and cell death. Honokiol markedly activated cellular 15-LOX-1 expression and 13-S-hydroxyoctadecadienoic acid (a primary product of 15-LOX-1 metabolism of linoleic acid) production. 15-LOX-1 siRNA could reverse the honokiol-induced down-regulation of PPAR-? and COX-2, and cell apoptosis. 15-LOX-1 was markedly induced in tumours of xenograft mice treated with honokiol. Conclusions and implications: These findings suggest that induction of 15-LOX-1-mediated down-regulation of a PPAR-? and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer.

Liu, Shing Hwa; Shen, Chin Chang; Yi, Yu Chiao; Tsai, Jaw Ji; Wang, Chih Chien; Chueh, Ju Ting; Lin, Keh Liang; Lee, Tso Ching; Pan, Hung Chuan; Sheu, Meei Ling

2010-01-01

136

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

137

Regulation of Interleukin6 Promoter Activation in Gastric Epithelial Cells Infected with Helicobacter pylori  

Microsoft Academic Search

RANTES, a CC chemokine, plays an important role in the inflammatory response associated with Helico- bacter pylori infection. However, the mechanism by which H. pylori induces RANTES expression in the gastric mucosa is unknown. We cocultured gastric epithelial cells with wild-type H. pylori, isogenic oipA mutants, cag pathogenicity island (PAI) mutants, or double knockout mutants. Reverse transcriptase PCR showed that

Hong Lu; Jeng Yih Wu; Takahiko Kudo; Tomoyuki Ohno; David Y. Graham; Yoshio Yamaoka

2005-01-01

138

The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in rats.  

PubMed

Garcinia cambogia extract is a herbal preparation that has been suggested as useful in the treatment of gastrointestinal disorders. In the present study this drug was tested for its antiulcerogenic effect. Oral pretreatment with Garcinia cambogia fruit extract (1 g/kg body wt/day) for 5, 10 or 15 days protected the gastric mucosa against the damage induced by indomethacin (20 mg/kg body wt). The volume and acidity of the gastric juice decreased in the pretreated rats. The glycoprotein levels of the gastric contents which were decreased in the untreated rats, maintained near normal levels in the pretreated rats. Protein which was elevated in the gastric juice of untreated rats, showed near normal levels in the pretreated rats. Garcinia cambogia was able to decrease the acidity and to increase the mucosal defence in the gastric areas, thereby justifying its use as an antiulcerogenic agent. PMID:11807973

Mahendran, P; Vanisree, A J; Shyamala Devi, C S

2002-02-01

139

Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A 2A adenosine receptor in rats  

Microsoft Academic Search

Background  Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin induce gastric mucosal lesions in part by the activation\\u000a of inflammatory cells and the production of proinflammatory cytokines. The activation of adenosine A2A receptors inhibits inflammation by increasing cyclic AMP in leukocytes and reducing both the production of various proinflammatory\\u000a cytokines and neutrophil chemotaxis. The aim of present study was to determine whether

Shigeto Koizumi; Masaru Odashima; Michiro Otaka; Mario Jin; Joel Linden; Sumio Watanabe; Hirohide Ohnishi

2009-01-01

140

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents.  

PubMed

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound. PMID:21702226

Onasanwo, Samuel A; Singh, Neetu; Olaleye, Samuel B; Palit, Gautam

2011-06-01

141

Effects of EM574 and cisapride on gastric contractile and emptying activity in normal and drug-induced gastroparesis in dogs.  

PubMed

EM574, an erythromycin derivative and potent motilin receptor agonist, is now undergoing clinical trials as a gastroprokinetic drug. The aim of this study was to compare the effect of EM574 with that of cisapride on gastric motility and emptying in normal and gastroparesis dogs. Six dogs were each implanted with two duodenal cannulas for infusion of phenolsulfonphthalein into the proximal duodenum and for aspiration of luminal samples from the distal duodenum. Both solid and liquid gastric emptying were determined by a novel freeze-drying method developed in our laboratory. A freeze-dried standard meal (100 g, 400 kcal) was given with 100 ml normal saline containing 15 g of polyethylene glycol as a liquid marker. Gastric muscle contractility was measured by means of a force transducer implanted on the gastric antrum. EM574 (3-30 microgram/kg) and cisapride (0.3-3.0 mg/kg) were administered intraduodenally at the start of feeding. Clonidine (3-30 microgram/kg) was injected subcutaneously 15 min before feeding to induce gastroparesis. EM574 and cisapride both enhanced gastric muscle contractility in a dose-dependent manner. EM574 (30 microgram/kg and 10 microgram/kg) significantly accelerated gastric emptying of solids and liquids, respectively. Cisapride (1 mg/kg) significantly accelerated solid gastric emptying, but 3.0 mg/kg significantly delayed liquid gastric emptying. Clonidine (10 and 30 microgram/kg) significantly delayed solid and liquid gastric emptying and reduced gastric muscle contractility. EM574, at a dose of 30 microgram/kg, completely restored solid and liquid gastric emptying and muscle contractility to the normal range in dogs with clonidine-induced gastroparesis. Cisapride (1 mg/kg) restored liquid gastric emptying in dogs with gastroparesis to the normal range and partially restored solid emptying. EM574 accelerated gastric muscle contractility and emptying of solids and liquids in normal dogs. The stimulating activity of EM574 on gastric muscle contractility and emptying was comparable to that of cisapride, but EM574 was as effective as cisapride in normalizing gastric muscle contractility and emptying in dogs with clonidine-induced gastroparesis. PMID:9808701

Tanaka, T; Mizumoto, A; Mochiki, E; Suzuki, H; Itoh, Z; Omura, S

1998-11-01

142

Inhibitory activities and attenuated expressions of 5-LOX with red ginseng in Helicobacter pylori-infected gastric epithelial cells.  

PubMed

Our recent studies documented that red ginseng extract (RGE, isolates from steamed and dried Panax ginseng, C.A. Meyer) can inhibit Helicobacter pylori-induced mitogen-activated protein kinase (MAPK) signaling with repressing either nuclear factor (NF)-kappaB-DNA binding activity or releases of IL-8 and COX-2 in gastric epithelial cells (Dig Dis Sci 50:1218-1227, 2005). We extended the experiment to prove whether RGE influences 5-lipoxygenase (5-LOX) pathway, thereby suppressing the biosynthesis of 5(S)-HETE. The 5-LOX enzyme activities were measured by thin layer chromatography using (14)C-labeled arachidonic acid (AA) and quantified by reverse phase-high performance liquid chromatography in human gastric adenocarcinoma (AGS) cells cocultured with H pylori (ATCC 43504 strain) with or without pretreatment of RGE. Western blotting analyses for MAPK signaling and 5-LOX, reverse transcriptase polymerase chain reaction for interleukin-8, and electrophoretic mobility shift assay for NF-kappaB-DNA binding were done, respectively. H pylori infection increased exclusively 5-LOX enzyme activity and RGE inhibited H pylori-stimulated 5-LOX activity, resulting in suppression of 5(S)-HETE generations from AA. RGE inactivated c-jun phosphorylation and repressed redox-sensitive transcriptional activation, led to reduced expression of IL-8 and 5-LOX mRNA in gastric mucosal cells, of which action was very similar to known LOX inhibitor, 200 mumol of geraniin. RGE could be phytoceutical against H pylori infection-associated gastric inflammation through its LOX-inhibiting actions, inhibitory 5-LOX enzyme activity, and attenuating its expression. PMID:17333352

Park, Soojin; Yeo, Marie; Jin, Joo-Hyun; Lee, Kee-Myung; Kim, Sung Soo; Choi, Sang Yoon; Hahm, Ki-Baik

2007-02-27

143

A synergistic interaction between transcription factors nuclear factor-?B and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion  

PubMed Central

Background The transcription factor nuclear factor-?B (NF-?B) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-?B and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells. Methods Immunohistochemistry for NF-?B p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-?B inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-?B repressor mutant of I?B?, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. Results NF-?B and STAT3 were constitutively activated and were positively correlated (P?=?0.038) in gastric cancer tissue specimens. In cell culture experiments, NF-?B inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-?B activation. Moreover, both NF-?B inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-?B activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P?=?0.001 and P?=?0.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. Conclusion NF-?B and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-?B and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.

2013-01-01

144

Abnormal PTEN expression in portal hypertensive gastric mucosa: a key to impaired PI 3-kinase/Akt activation and delayed injury healing?  

PubMed

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual-specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids. PTEN inhibits activation of Akt, the downstream effector of PI 3-kinase, which is integral to cell proliferation, migration, survival, and angiogenesis essential for tissue injury healing. PTEN expression and activation during injury healing remain unexplored. Portal hypertensive (PHT) gastric mucosa has impaired injury healing, but the underlying mechanisms remain unknown. We investigated whether impaired healing of injured PHT gastric mucosa is due to abnormal PTEN expression/activation that leads to decreased Akt activation. We also investigated the possible involvement of Egr-1, which regulates PTEN in some cells (e.g., fetal kidney epithelial cells), and TNF-alpha, which can induce Egr-1 expression. In PHT gastric mucosa 6 h after injury, PTEN protein levels were increased by 2.7-fold; unphosphorylated PTEN (reflecting activated PTEN) was increased by 2.4-fold; Akt phosphorylation (reflecting Akt activation) was reduced by 2-fold; and Egr-1 expression was increased by 3.3-fold vs. normal gastric mucosa. TNF-alpha neutralization reversed all of the above abnormalities in PHT gastric mucosa, reduced mucosal injury, and enhanced healing. We conclude that, in injured PHT gastric mucosa, overexpressed/activated PTEN leads to the reduced activation of the PI 3-kinase/Akt pathway that results in impaired injury healing. PMID:14525948

Tsugawa, Kouji; Jones, Michael K; Akahoshi, Tomohiko; Moon, Woo Sung; Maehara, Yoshihiko; Hashizume, Makoto; Sarfeh, I James; Tarnawski, Andrzej S

2003-10-02

145

[Relationship of enzyme activity of the gastric mucosa with microcirculation and acid output].  

PubMed

The aim was to study the gastric blood flow due to acid output and enzyme systems of GM. The study included 14 healthy young and 20 healthy elderly people without atrophic changes in GM. Blood flow in microvessels GM was determined by laser Doppler flowmeter, acid output was assessed by 24-hours pH-monitoring, the activity of H(+)-K(+)-ATPase and nitric oxide synthase in biopsies GM was determined by standard biochemical methods. In normal elderly people a significant reduction in blood flow in the microvessels of the secretory zone of GM (large curvature, front and back wall in the body stomach) accompanied by a decrease in the activity of NO-synthase was found. Acid output and activity of H(+)-K(+)-ATPase of parietal cells in the same area do not decreases with age. However, older patients demonstrated a higher level of blood flow in the secretory zone combined with a higher acid output, which indicates that the increase in the level of blood flow values for hydrochloric acid secretion in older people. PMID:23289230

Korkushko, O V; Shatilo, V B; Gavalko, Iu V; Grib, O N; Bagri?, A S; Ostapchenko, L I; Strotskaia, E A

2012-01-01

146

Ethanol injury triggers activation of adrenomedullin and its receptor genes in gastric mucosa.  

PubMed

Adrenomedullin (AM) is a potent vasodilatory peptide, which is present in the stomach. However, its precise function in the gastric mucosa is unknown. The expression and localization of AM and its receptor in gastric mucosa injured by ethanol also have not been explored, forming the basis for this study. Gastric samples of rats were obtained at 0 and 8 hr and 1, 2, and 4 days after intragastric administration of 100% ethanol. By RT-PCR, AM mRNA expression in gastric mucosa at 8 and 24 hr following ethanol injury was increased by 2-fold and by 2.5-fold (both P<0.01), respectively, and returned to normal at two days. AM receptor mRNA expression was increased by 2.7-fold, 2.3-fold, and 2.4-fold at 8, 24, and 48 hr, respectively (all P<0.01), and returned to normal at four days. By in situ hybridization, AM and AM receptor mRNAs were present in normal gastric mucosa and up-regulated in gastric mucosa following ethanol injury. The immunohistochemical signal for AM was significantly increased in the mucosa bordering erosion sites. We conclude that ethanol injury up-regulates the expression of both AM and AM receptor in gastric mucosa. PMID:10489925

Wang, H; Tomikawa, M; Jones, M K; Sarfeh, I J; Tarnawski, A S

1999-07-01

147

Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer  

PubMed Central

Background Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models. Results Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE)-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE) resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2 pathway in mice (K19-Wnt1/C2mE mice) further reproduce features of human gastric intestinal-type tumors. Conclusion We demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especially K19-Wnt1/C2mE mice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers.

2009-01-01

148

Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production  

PubMed Central

Chronic infection, such as Helicobacter pylori infection, has been associated with the development of gastric cancer (GC). Pathogen-associated molecular patterns can trigger inflammatory responses via Toll-like receptors (TLRs) in GC. Here we showed that Toll-like receptor 4 (TLR4) was highly expressed in GC cells and was associated with the aggressiveness of GC. The binding of lipopolysaccharide (LPS) to TLR4 on GC cells enhanced proliferation without affecting apoptosis. Higher level of reactive oxygen species (ROS) was induced after activation of TLR4 signaling in GC. Using oxidase inhibitors and antioxidants, we found that mitochondrial ROS (mROS) was major source of TLR4-stimulated ROS generation. This elevated mROS production can be inhibited by diphenylene iodonium (DPI), and the blocking of the mROS production rather than ROS neutralization resulted in cell cycle arrest and the loss of mitochondrial potential, which were plausible reason for decreased cell viability. Furthermore, the increased mROS owing to TLR4 signaling resulted in the activation of Akt phosphorylation and NF-?B p65 nuclear translocation. Altogether, these results reveal a novel pathway linking innate immune signaling to GC cell proliferation, implicate mROS as an important component of cell survival signals and further establish mitochondria as hubs for GC therapies.

Yuan, X; Zhou, Y; Wang, W; Li, J; Xie, G; Zhao, Y; Xu, D; Shen, L

2013-01-01

149

Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production.  

PubMed

Chronic infection, such as Helicobacter pylori infection, has been associated with the development of gastric cancer (GC). Pathogen-associated molecular patterns can trigger inflammatory responses via Toll-like receptors (TLRs) in GC. Here we showed that Toll-like receptor 4 (TLR4) was highly expressed in GC cells and was associated with the aggressiveness of GC. The binding of lipopolysaccharide (LPS) to TLR4 on GC cells enhanced proliferation without affecting apoptosis. Higher level of reactive oxygen species (ROS) was induced after activation of TLR4 signaling in GC. Using oxidase inhibitors and antioxidants, we found that mitochondrial ROS (mROS) was major source of TLR4-stimulated ROS generation. This elevated mROS production can be inhibited by diphenylene iodonium (DPI), and the blocking of the mROS production rather than ROS neutralization resulted in cell cycle arrest and the loss of mitochondrial potential, which were plausible reason for decreased cell viability. Furthermore, the increased mROS owing to TLR4 signaling resulted in the activation of Akt phosphorylation and NF-?B p65 nuclear translocation. Altogether, these results reveal a novel pathway linking innate immune signaling to GC cell proliferation, implicate mROS as an important component of cell survival signals and further establish mitochondria as hubs for GC therapies. PMID:24030146

Yuan, X; Zhou, Y; Wang, W; Li, J; Xie, G; Zhao, Y; Xu, D; Shen, L

2013-09-12

150

Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes  

Microsoft Academic Search

The protein kinase C (PKC) signaling pathwayplays a key role in tumor cell proliferation,differentiation, and apoptosis. Gastric cancer usuallypossesses a higher level of PKC activity than normaltissue. We evaluated inhibition of PKC activity inapoptosis induction of gastric cancer cells and theexpression profile of apoptosis-related genes. Gastriccancer cells (AGS) were incubated with two highlyspecific PKC inhibitors (RO-31-8220 and chelerythrine).Cell viability and

G. H. Zhu; B. C. Y. Wong; M. C. Eggo; S. T. Yuen; K. C. Lai; S. K. Lam

1999-01-01

151

NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts.  

PubMed

Myofibroblasts play central roles in wound healing, deposition of the extracellular matrix and epithelial function. Their functions depend on migration and proliferation within the subepithelial matrix, which results in accelerated cellular metabolism. Upregulated metabolic pathways generate protons which need to be excreted to maintain intracellular pH (pH(i)). We isolated human gastric myofibroblasts (HGMs) from surgical specimens of five patients. Then we characterized, for the first time, the expression and functional activities of the Na(+)/H(+) exchanger (NHE) isoforms 1, 2 and 3, and the functional activities of the Na(+)/HCO(3)(-) cotransporter (NBC) and the anion exchanger (AE) in cultured HGMs using microfluorimetry, immunocytochemistry, reverse transcription polymerase chain reaction and immunoblot analysis. We showed that NHE1-3, NBC and AE activities are present in HGMs and that NHE1 is the most active of the NHEs. In scratch wound assays we also demonstrated (using the selective NHE inhibitor HOE-642) that carbachol and insulin like growth factor II (IGF-II) partly stimulate migration of HGMs in a NHE1-dependent manner. EdU incorporation assays revealed that IGF-II induces proliferation of HGMs which is inhibited by HOE-642. The results indicate that NHE1 is necessary for IGF-II-induced proliferation response of HGMs. Overall, we have characterized the pH(i) regulatory mechanisms of HGMs. In addition, we demonstrated that NHE1 activity contributes to both IGF-II- and carbachol-stimulated migration and that it is obligatory for IGF-II-induced proliferation of HGMs. PMID:22138972

Czepán, Mátyás; Rakonczay, Zoltán; Varró, Andrea; Steele, Islay; Dimaline, Rod; Lertkowit, Nantaporn; Lonovics, János; Schnúr, Andrea; Biczó, György; Geisz, Andrea; Lázár, György; Simonka, Zsolt; Venglovecz, Viktória; Wittmann, Tibor; Hegyi, Péter

2011-12-06

152

Binge Eating, Quality of Life and Physical Activity Improve after Roux-en-Y Gastric Bypass for Morbid Obesity  

Microsoft Academic Search

Background: Severe obesity has been associated with disordered eating, impaired quality of life (QoL), and decreased physical activity.This\\u000a study examines changes in these variables 6 months after Roux-en-Y gastric bypass (RYGBP). Methods: 40 morbidly obese patients were evaluated at baseline and at 6 months after RYGBP on the following measures: Binge Eating\\u000a Scale, Three Factor Eating Questionnaire, Impact of Weight

Jarol Boan; Ronette L. Kolotkin; Eric C. Westman; Ross L. McMahon; John P. Grant

2004-01-01

153

Effects of vection-induced motion sickness on gastric myoelectric activity and oral-cecal transit time  

Microsoft Academic Search

The purpose of this study was to investigate the effects of vection-induced motion sickness on three cycle per minute gastric myoelectric activity and oral-cecal transit time. Forty-five subjects were exposed to a rotating optokinetic drum while electrogastrograms and subjective reports of symptoms were monitored. Prior to exposure, baseline breath hydrogen levels were established and subjects ingested vanilla pudding containing 10

Eric R. Muth; Robert M. Stern; Kenneth L. Koch

1996-01-01

154

Role of ghrelin-induced cSrc activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori  

Microsoft Academic Search

A peptide hormone, ghrelin, is recognized as an important modulator of gastric mucosal inflammatory responses to H. pylori through the regulation of nitric oxide synthase (NOS) system. As cSrc kinase plays a major role in transduction of signals\\u000a that regulate the activity of NOS isozyme system, we investigated the influence of H. pylori LPS on the processes associated with Src

B. L. Slomiany; A. Slomiany

2011-01-01

155

Changes in brain activation to food pictures after adjustable gastric banding  

Microsoft Academic Search

BackgroundAdjustable gastric banding is an effective weight-loss treatment, but little is known about the neural mechanisms underlying weight loss. The purpose of the present study was to determine whether gastric banding affects brain function in regions previously implicated in food motivation, reward, and cognitive control. The setting for the study was the University of Missouri-Kansas City, Department of Psychology; Hoglund

Jared M. Bruce; Laura Hancock; Amanda Bruce; Rebecca J. Lepping; Laura Martin; Jennifer D. Lundgren; Steven Malley; Laura M. Holsen; Cary R. Savage

156

Anti-inflammatory activity and effect on gastric acid secretion of dehydroleucodine isolated from Artemisia douglasiana  

Microsoft Academic Search

The effect of Dehydroleucodine (DhL) on gastric acid secretion in rats was investigated at a dose of 40mg\\/kg, while its anti-inflammatory effect was investigated in two experimental models: arthritis induced by Freund’s adjuvant carrageenan- and cotton pellet-induced granuloma. DhL did not inhibit gastric acid secretion, suggesting that its anti-ulcerogenic effect can be attributed to its action on the mucosa defense

T Guardia; A. O Juarez; E Guerreiro; J. A Guzmán; L Pelzer

2003-01-01

157

Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats  

Microsoft Academic Search

Background & Aims: Previous studies have shown that gastric ulceration stimulates epithelial cell proliferation and overexpression of epidermal growth factor (EGF) and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study was to investigate whether extracellular signal-regulated kinase (ERK) cascade is involved in the healing of experimental gastric ulcers. Methods: We studied EGF-R levels, EGF-R phosphorylation

Rama Pai; Masayuki Ohta; Rabiha M. Itani; I. James Sarfeh; Andrzej S. Tarnawski

1998-01-01

158

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

PubMed

Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, long-term hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion. PMID:17278212

Cui, Guanglin; Waldum, Helge L

2007-01-28

159

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

160

Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives.  

PubMed

A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2-pyrazoline derivatives were synthesized by carrying a nitrate ester group or an oxime group onto the prepared pyrazoline derivatives through different spacers. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced rat paw edema and compared to a well-known NSAID, indomethacin as a reference drug. The ability of the prepared compounds to induce gastric toxicity was also evaluated. Most of the prepared compounds showed significant anti-inflammatory activity at the injected dose (100mg/kg) but they were safer than indomethacin in regard to gastric toxicity. The incorporation of the NO-donating group into the parent pyrazoline derivatives caused a non-significant reduction in the anti-inflammatory activity while a marked decrease in gastric ulcerations induced by their parent pyrazolines was observed. PMID:18722034

Shoman, Mai E; Abdel-Aziz, Mohamed; Aly, Omar M; Farag, Hassan H; Morsy, Mohamed A

2008-07-16

161

Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass.  

PubMed

Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values activity, higher initial BMI, lower educational level, diabetes, and decreased attendance at postoperative appointments had an adverse effect on weight loss after RYGB. A model including these five factors accounts for 41% of the observed variability in weight loss (adjusted r(2) = 0.41). In this cohort, higher initial BMI and limited physical activity were the strongest predictors of decreased excess weight loss following RYGB. Limited physical activity may be particularly important because it represents an opportunity for potentially meaningful pre- and postsurgical intervention to maximize weight loss following RYGB. PMID:18997674

Hatoum, Ida J; Stein, Heather K; Merrifield, Benjamin F; Kaplan, Lee M

2008-11-06

162

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

163

Helicobacter pylori culture supernatant interferes with epidermal growth factor-activated signal transduction in human gastric KATO III cells.  

PubMed Central

The mechanisms by which Helicobacter pylori infection leads to gastroduodenal ulceration remain poorly understood. Previous studies have shown that H. pylori vacuolating cytotoxin (VacA) inhibits proliferation of gastric epithelial cells, which suggests that H pylori may interfere with gastric mucosal repair mechanisms. In this study, we investigated the effects of H. pylori broth culture supernatants on epidermal growth factor (EGF)-mediated signal transduction pathways in a gastric carcinoma cell line (KATO III). Exposure of these cells to EGF resulted in increased expression and phosphorylation of the EGF receptor (EGF-R), increased ERK2 activity and phosphorylation, and increased c-fos protein levels. Preincubation of cells with broth culture supernatant from VacA (+) H. pylori strain 60190 inhibited the capacity of EGF to induce each of these effects. In contrast, preincubation of cells with broth culture supernatant from an isogenic VacA-mutant strain (H. pylori 60190-v1) failed to inhibit the effects of EGF. These results suggest that the H. pylori vacuolating cytotoxin interferes with EGF-activated signal transduction pathways, which are known to be essential for cell proliferation and ulcer healing. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5

Pai, R.; Wyle, F. A.; Cover, T. L.; Itani, R. M.; Domek, M. J.; Tarnawski, A. S.

1998-01-01

164

Antitumour activity of S-1 in combination with cetuximab on human gastric cancer cell lines in vivo.  

PubMed

This study aimed to assess the antitumour effect of a combination of cetuximab (Erbitux, a chimeric anti-epidermal growth factor receptor (EGFR) monoclonal antibody) and S-1, an oral 5-fluorouracil prodrug, on gastric cancer cell lines in vivo. Gastric cancer cell lines (SC-2 and SC-4) were transplanted subcutaneously into nude mice. In both cell lines, which have high EGFR expression and harbour K-ras wild-type alleles, treatment with a combination of cetuximab and oral S-1 resulted in significantly higher antitumour activity than treatment with cetuximab or S-1 alone. To investigate this potentiation of antitumour activity, the expression levels of thymidylate synthase (TYMS) were measured following administration of cetuximab. Cetuximab induced a decrease in expression of TYMS mRNA and protein. These findings suggest that cetuximab-mediated down-regulation of TYMS enhances the antitumour effect of S-1 and provide a rationale for designing novel combination chemotherapy regimens for patients with advanced gastric cancer. PMID:22110188

Kobunai, Takashi; Watanabe, Toshiaki; Fukusato, Toshio

2011-11-01

165

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

2012-11-06

166

Gastric cancer  

SciTech Connect

This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer.

Douglass, H.O. (Dept. of Surgical Research, State Univ. of New York at Buffalo, NY (US))

1988-01-01

167

Thimerosal-Induced Apoptosis in Human SCM1 Gastric Cancer Cells: Activation of p38 MAP Kinase and Caspase3 Pathways without Involvement of [Ca2+]i Elevation  

Microsoft Academic Search

Thimerosal is a mercury-containing preservative in some vaccines. The effect of thimerosal on human gastric cancer cells is unknown. This study shows that in cultured human gastric cancer cells (SCM1), thimerosal reduced cell viability in a concen- tration- and time-dependent manner. Thimerosal caused apopto- sis as assessed by propidium iodide-stained cells and caspase-3 activation. Although immunoblotting data revealed that thimer-

Shiuh-Inn Liu; Chorng-Chih Huang; Chun-Jen Huang; Being-Whey Wang; Po-Min Chang; Y.-C. Fang; W.-C. Chen; J.-L. Wang; Y.-C. Lu; S.-T. Chu; C.-T. Chou; C.-R. Jan

2007-01-01

168

RUNX3 Suppresses Gastric Epithelial Cell Growth by Inducing p21WAF1\\/Cip1 Expression in Cooperation with Transforming Growth Factor  Activated SMAD  

Microsoft Academic Search

RUNX3 has been suggested to be a tumor suppressor of gastric cancer. The gastric mucosa of the Runx3-null mouse develops hyperplasia due to enhanced proliferation and suppressed apoptosis accompanied by a decreased sensitivity to transforming growth factor 1 (TGF-1). It is known that TGF-1 induces cell growth arrest by activating CDKN1A (p21WAF1\\/Cip1), which encodes a cyclin-dependent kinase inhibitor, and this

Xin-Zi Chi; Jeung-Ook Yang; Kwang-Youl Lee; Kosei Ito; Chohei Sakakura; Qing-Lin Li; Hye-Ryun Kim; Eun-Jeung Cha; Yong-Hee Lee; Atsushi Kaneda; Toshikazu Ushijima; Wun-Jae Kim; Yoshiaki Ito; Suk-Chul Bae

2005-01-01

169

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients--evaluation of 24-h pH monitoring.  

PubMed

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradication was achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7 pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period. PMID:11595477

Rácz, I; Szabó, A; Csöndes, M; Pécsi, G; Goda, M

170

Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.  

PubMed

In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration. PMID:10791688

Tarnawski, A S; Tomikawa, M; Ohta, M; Sarfeh, I J

171

Helicobacter pylori promotes invasion and metastasis of gastric cancer cells through activation of AP-1 and up-regulation of CACUL1.  

PubMed

Infection with Helicobacter pylori is important in the development and progression of gastric cancer. However, the mechanisms that regulate this activation in gastric tumors remain elusive. CACUL1 has been cloned and identified as a novel gene that is expressed in many types of cancer and is involved in cell cycle regulation and tumor growth. The current study aimed to examine the expression of CACUL1 in gastric cancer samples and analyze its correlation with H. pylori infection. We found that CACUL1 was highly expressed in gastric cancer tissues and negatively correlated with gastric cancer differentiation and TNM stage. In addition, CACUL1 expression was high in H. pylori-infected tissues compared with H. pylori non-infected tissue. We found that H. pylori could up-regulate CACUL1 expression through activating protein 1. The up-regulation of CACUL1 expression could promote matrix metalloproteinase 9 and Slug expression to increase invasion and metastasis of tumor cells. These results suggested that H. pylori-triggered CACUL1 production occurred in an activating protein 1-dependent manner and regulated matrix metalloproteinase 9 and Slug expression to affect the invasion and metastasis of tumor cells. Therefore, CACUL1 is a potential therapeutic target for the treatment of aggressive gastric cancer. PMID:24004834

Kong, Ying; Ma, Li-Qing; Bai, Pei-Song; Da, Rong; Sun, Hong; Qi, Xiao-Gai; Ma, Jie-Qun; Zhao, Ru-Ming; Chen, Nan-Zheng; Nan, Ke-Jun

2013-09-01

172

Activities of Daily Living and Quality of Life of Elderly Patients After Elective Surgery for Gastric and Colorectal Cancers  

PubMed Central

Objective: To establish reliable standards for surgical application to elderly patients 75 years old or older with gastric or colorectal cancer with special reference to the postoperative recovery of activities of daily living (ADL) and quality of life (QOL). Summary Background Data: ADL and QOL are important outcomes of surgery for the elderly. However, there has been only limited evidence on the natural course of recovery of functional independence. Methods: Two hundred twenty-three patients 75 years old or older with gastric or colorectal cancer were prospectively examined. Physical conditions, ADL, and QOL were evaluated preoperatively and at the first, third, and sixth postoperative month. Results: The mortality and morbidity rates were 0.4% and 28%, respectively. Twenty-four percent of patients showed a decrease in ADL at 1 month postoperatively, but most patients recovered from this transient reduction, with only 3% showing a decline at the sixth postoperative month (6POM). ADL of these patients was likely to decrease after discharge from the hospital. QOL of the patients showed a recovery to an extent equal to or better than their average preoperative scores. Conclusions: Of the patients 75 years old or older who underwent elective surgery for gastric or colorectal cancer, only a few showed a protracted decline in ADL and most exhibited better QOL after surgery. This indicates that surgical treatment should be considered, whenever needed, for elderly patients 75 years old or older with gastric or colorectal cancer. Estimation of Physical Ability and Surgical Stress is useful for predicting postoperative declines in ADL and protracted disability; this could aid in establishing a directed rehabilitation program for preventing protracted disability in elderly patients.

Amemiya, Takeshi; Oda, Koji; Ando, Masahiko; Kawamura, Takashi; Kitagawa, Yuichi; Okawa, Yayoi; Yasui, Akihiro; Ike, Hideyuki; Shimada, Hiroshi; Kuroiwa, Kojiro; Nimura, Yuji; Fukata, Shinji

2007-01-01

173

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

174

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

2013-09-13

175

The H+/K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells.  

PubMed

Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 ?g/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment. PMID:23742858

Zhang, Qiaoyin; Huang, Nianyu; Wang, Junzhi; Luo, Huajun; He, Haibo; Ding, Mingruo; Deng, Wei-Qiao; Zou, Kun

2013-06-03

176

Quercetin prevents oxidative stress and NF-kappaB activation in gastric mucosa of portal hypertensive rats.  

PubMed

The present study was designed to investigate the effects of quercetin on oxidative stress and activation of nuclear factor kappa B (NF-kappaB) in an experimental model of portal hypertensive gastropathy induced by partial portal vein ligation (PPVL). Portal pressure was significantly elevated in PPVL rats. Transaminase and alkaline phosphatase activities were not significantly modified, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. The cytosolic concentration of thiobarbituric acid reactive substances and the lipoperoxidation measurement by chemiluminiscence were significantly increased. Superoxide dismutase activity in gastric mucosa was significantly reduced. Portal hypertensive gastropathy induced a marked activation of NF-kappaB, accompanied by a decrease in IkappaB protein levels and a significant induction of nitric oxide synthase (iNOS) protein. Administration of quercetin markedly alleviated histological abnormalities and inhibited oxidative stress and NF-kappaB activation. IkappaB decrease and induction of iNOS protein were partially prevented by quercetin. Quercetin treatment, by abolishing the NF-kappaB signal transduction pathway, may block the production of noxious mediators involved in the pathogenesis of portal hypertensive gastropathy. PMID:15476665

Moreira, Andrea J; Fraga, Christina; Alonso, María; Collado, Pilar S; Zetller, Claudio; Marroni, Claudio; Marroni, Norma; González-Gallego, Javier

2004-11-15

177

Effect of EM574 on Postprandial Pancreaticobiliary Secretion, Gastric Motor Activity, and Emptying in Conscious Dogs  

Microsoft Academic Search

EM574, an erythromycin derivative and a potentmotilin receptor agonist, is now under clinical trial asa gastroprokinetic drug. The aim of this study was toestimate the effect of EM574 on postprandial pancreaticobiliary secretion, gastric motoractivity, and emptying in conscious dogs. Five mongreldogs were prepared. Indwelling cannulas for bothinfusion of phenolsulfonphthalein and aspiration ofluminal samples were inserted into the proximal anddistal duodenum,

Toshiyuki Tanaka; Akiyoshi Mizumoto; Erito Mochiki; Hideki Suzuki; Zen Itoh; Satoshi Omura

1999-01-01

178

Capacity for Physical Activity Predicts Weight Loss After Roux-en-Y Gastric Bypass  

Microsoft Academic Search

Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for

Ida J. Hatoum; Heather K. Stein; Benjamin F. Merrifield; Lee M. Kaplan

2009-01-01

179

Effect of calcitonin on gastric emptying in patients with an active duodenal ulcer.  

PubMed Central

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.

Jonderko, K

1989-01-01

180

Helicobacter pylori-induced loss of survivin and gastric cell viability is attributable to secreted bacterial gamma-glutamyl transpeptidase activity.  

PubMed

Helicobacter pylori is the etiologic agent of a series of gastric pathologies that may culminate in the development of gastric adenocarcinoma. An initial step in this process is the loss of glandular structures in the gastric mucosa, presumably as the consequence of increased apoptosis and reduced cellular regeneration, which may be attributed to the combination of several bacterial and host factors and to an unfavorable proinflammatory environment. In a previous study, we showed that survivin, a member of the inhibitor of apoptosis protein family, is expressed in the normal human gastric mucosa and that its levels decrease in the mucosa of infected patients and in gastric cells exposed in culture to the bacteria, coincident with increased cell death in the latter case. We investigated the bacterial factors responsible for loss of survivin in gastric cells exposed to H. pylori. The results of this study indicated that the loss of survivin due to H. pylori infection involves proteasome-mediated degradation of the protein. Studies with isogenic mutants deficient in either CagA, VacA, lipopolysaccharide, or gamma-glutamyl transpeptidase (GGT) implicated the latter in H. pylori-induced loss of survivin and cell viability. Moreover, experiments with the GGT inhibitor 6-diazo-5-oxo-l-norleucine and purified recombinant GGT protein indicated that secreted bacterial GGT activity was required and sufficient to induce these effects. PMID:23847060

Valenzuela, Manuel; Bravo, Denisse; Canales, Jimena; Sanhueza, Carlos; Díaz, Natalia; Almarza, Oscar; Toledo, Héctor; Quest, Andrew F G

2013-07-11

181

Gastric Dysfunction  

Microsoft Academic Search

Parkinson’s disease (PD) is frequently regarded as a pure motor disorder. However, this degenerative illness affects also\\u000a the autonomic as well as the enteric nervous systems. Impairment of gastric motility has been found in 70% of patients with\\u000a PD. Neuropathological changes have been described in patients with PD in all parts of the nervous system responsible for gastric\\u000a motility. Gastric

Tanya Gurevich; Amos D. Korczyn; Nir Giladi

182

Helicobacter and Gastric Malignancies  

PubMed Central

Individuals infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of environmental, host genetic, and bacterial factors associated with risk of gastric cancer, to molecular and cell biology approaches aiming at understanding the interaction between H. pylori and the transforming epithelial cell. In this review an account of the last year’s research activity on the relationship between H. pylori and gastric cancer will be given.

Ferreira, Antonio Carlos; Isomoto, Hajime; Moriyama, Masatsugu; Fujioka, Toshio; Machado, Jose Carlos; Yamaoka, Yoshio

2011-01-01

183

Constitutive activation of glycogen synthase kinase-3? correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer  

PubMed Central

Background Aberrant regulation of glycogen synthase kinase-3? (GSK-3?) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3? phosphorylated at Tyr216 (pGSK-3?) and its relationship with other tumor-associated proteins in human gastric cancers. Methods Immunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3? inhibitor lithium chloride (LiCl) for immunoblot analysis. Results We found that pGSK-3? was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3? inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3? expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAI1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl. Conclusions GSK-3? activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3? activation is a useful prognostic marker for the early-stage gastric cancer.

2010-01-01

184

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-Muńiz, Elizabeth; Kauffman, Frederick C; Sanchez, Rosa I; Mesia-Vela, Sonia

2005-11-28

185

Calebin-A induces apoptosis and modulates MAPK family activity in drug resistant human gastric cancer cells.  

PubMed

This study is the first to investigate Calebin-A, a natural compound present in Curcuma longa, which inhibits cell growth and induce apoptosis in SGC7901/VINCRISTINE cells, a multidrug resistant (MDR) human gastric adenocarcinoma cell line. Our data suggest the drug efflux function of P-glycoprotein was inhibited by Calebin-A treatment, while the expression level of P-glycoprotein was not affected. Additionally, co-treatment of Calebin-A and vincristine resulted in a remarkable reduction in S phase and G2/M phase arrest in SGC7901/VINCRISTINE cells. Calebin-A was also found to modulate the activities of mitogen-activated protein kinase (MAPK) family members, which includes decreased c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and increased protein kinase of 38 kDa (p38) activity. These results suggest that Calebin-A might be an effective compound for the treatment of human gastric and other MDR cancers. PMID:18619958

Li, Yan; Li, Shaoqing; Han, Yueheng; Liu, Junye; Zhang, Jian; Li, Fuyang; Wang, Yun; Liu, Xinping; Yao, Libo

2008-06-22

186

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway.  

PubMed

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-alpha in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-alpha neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-alpha stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P <.01); (2) membrane translocation (P <.05) and phosphorylation (P <.05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P <.01) and activity (P <.01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P <.001). Neutralizing anti-TNF-alpha antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-alpha stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway. PMID:11826414

Kawanaka, Hirofumi; Jones, Michael K; Szabo, Imre L; Baatar, Dolgor; Pai, Rama; Tsugawa, Kouji; Sugimachi, Keizo; Sarfeh, I James; Tarnawski, Andrzej S

2002-02-01

187

Role of nitrosation in the mutagenic activity of coal dust: a postulation for gastric carcinogenesis in coal miners  

SciTech Connect

The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system. Coal dust solvent extracts were either nonmutagenic or very weakly mutagenic with S9 activation. High mutagenic activities, however, were found when extracts of bituminous, subbituminous, and lignite coal dusts were reacted with nitrite under an acidic condition. Formation of mutagens from coal dust extracts by nitrosation was highest at pH 3.2 and decreased with increasing pH in the reation mixture. Mutagenic activity appeared to be independent of metabolic activation. The mutagens formed from nitrosation of coal dust extracts induced frameshift mutations. The results reported here may have possible implications for the explanation of an elevated incidence of gastric cancer in coal miners.

Whong, W.Z.; Long, R.; Ames, R.G.; Ong, T.M.

1983-12-01

188

Scopadulciol, an inhibitor of gastric H+, K(+)-ATPase from Scoparia dulcis, and its structure-activity relationships.  

PubMed

A new tetracyclic diterpenoid, scopadulciol [3], together with 6-methoxybenzoxazolinone, glutinol, and acacetin, was isolated from the 70% EtOH extract of Scoparia dulcis collected in Taiwan. Its structure was elucidated to be 6 beta-benzoyl-12-methyl-13-oxo-9(12)a,9(12)b-dihomo-18-podocarpanol on the basis of spectral data. It mildly inhibited hog gastric H+, K(+)-ATPase. Examination of the inhibitory activities of derivatives of scopadulcic acid B [2], including 3, revealed that methylation of the carboxyl group and introduction of an acetyl group or oxime at C-13 or C-18 markedly enhanced the inhibitory activity, while debenzoylation reduced the activity. Among the 30 compounds tested, compound 12, a methyl ester of scopadulcic acid B [2], showed the most potent activity. PMID:1659612

Hayashi, T; Asano, S; Mizutani, M; Takeguchi, N; Kojima, T; Okamura, K; Morita, N

189

Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes.  

PubMed

In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and L: -glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions. PMID:21132420

Kitamura, Akihiko; Sato, Wataru; Uneyama, Hisayuki; Torii, Kunio; Niijima, Akira

2010-12-04

190

Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial  

Microsoft Academic Search

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m?2 every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4–36.9%)). In total, 16 patients achieved stable disease

C-H Köhne; R Catane; B Klein; M Ducreux; P Thuss-Patience; N Niederle; M Gips; P Preusser; A Knuth; M Clemens; R Bugat; I Figer; A Shani; B Fages; D Di Betta; C Jacques; H J Wilke

2003-01-01

191

Effect of Berkefeld filtration on the binding activity of human gastric juice  

PubMed Central

The intrinsic factor content of Berkefeld-filtered human gastric juice has been studied. This appears to vary with the pH at which filtration is carried out and also between individual filters. Significant losses of intrinsic factor may result from filtration and complete loss when filtration is carried out at a low pH. The most suitable pH for filtration appears to be in the range pH 7 to 8.

Dellipiani, A. W.; Samson, R. R.; Girdwood, R. H.

1969-01-01

192

Alterations of Hormonally Active Fibroblast Growth Factors after Roux-en-Y Gastric Bypass Surgery  

Microsoft Academic Search

Thirty-five morbidly obese patients underwent Roux-en-Y gastric bypass surgery (RYGB). In addition to weight loss, these patients showed significant improvement of insulin resistance and a reduction of hepatic fat content. Three months after surgery, the serum bile salts were slightly but significantly elevated, and the levels of the endocrine-acting fibroblast growth factor 19 (FGF19) and FGF21 were increased. FGF19 and

Peter L. M. Jansen; Jochem van Werven; Edo Aarts; Frits Berends; Ignace Janssen; Jaap Stoker; Frank G. Schaap

2011-01-01

193

Inhibition of Lipid Peroxidation, NF-?B Activation and IL8 Production by Rebamipide in Helicobacter pylori-Stimulated Gastric Epithelial Cells  

Microsoft Academic Search

The present study aimed to investigate whether rebamipide, a novel antiulcer agent that has an oxygen radical scavenging activity, would inhibit lipid peroxidation, NF-?B activation, and IL-8 production by H. pylori. Human gastric epithelial cells (AGS and KATO III), treated with rebamipide or not were incubated in the absence or the presence of H. pylori. As a result, H. pylori

Hyeyoung Kim; Jeong Yeon Seo; Kyung Hwan Kim

2000-01-01

194

Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo.  

PubMed

Cisplatin is an anticancer agent that is effective against several types of cancer, including gastric cancer. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to clarify how triptolide, an active component extracted from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F (TWHF), enhances cisplatin-induced cytotoxicity in gastric cancer SC-M1 cells. After low-dose combined treatments with triptolide and cisplatin, a decrease in viability with a concomitant increase in apoptosis was observed in SC-M1 cells but not in normal cells. Apoptosis induced by the combined treatments was accompanied by loss of mitochondrial membrane potential and release of cytochrome c. Triptolide increased the cisplatin-induced activation of caspase-3 and caspase-9 and the downstream cleavage of PARP in SC-M1 cells. Results of these in vitro experiments indicated that triptolide enhanced cytotoxicity in cisplatin-treated SC-M1 cells and that this effect is mediated by apoptosis through a mitochondrial pathway. Furthermore, using a SCID mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth via down-regulation of proliferating cell nuclear antigen expression without significant side effects. These results suggest that lower concentrations of cisplatin and triptolide used in combination may produce a synergistic anticancer effect that warrants further investigation for its potential clinical applications. PMID:22306340

Li, Chia-Jung; Chu, Ching-Yu; Huang, Lin-Huang; Wang, Ming-Hseng; Sheu, Lai-Fa; Yeh, Jih-I; Hsu, Hsue-Yin

2012-02-01

195

Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer  

Microsoft Academic Search

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and

P P Aung; N Oue; Y Mitani; H Nakayama; K Yoshida; T Noguchi; A K Bosserhoff; W Yasui

2006-01-01

196

Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3.  

PubMed

Cancer progression involves changes in extracellular proteolysis, but the contribution of stromal cell secretomes to the cancer degradome remains uncertain. We have now defined the secretome of a specific stromal cell type, the myofibroblast, in gastric cancer and its modification by proteolysis. SILAC labeling and COFRADIC isolation of methionine containing peptides allowed us to quantify differences in gastric cancer-derived myofibroblasts compared with myofibroblasts from adjacent tissue, revealing increased abundance of several proteases in cancer myofibroblasts including matrix metalloproteinases (MMP)-1 and -3. Moreover, N-terminal COFRADIC analysis identified cancer-restricted proteolytic cleavages, including liberation of the active forms of MMP-1, -2, and -3 from their inactive precursors. In vivo imaging confirmed increased MMP activity when gastric cancer cells were xenografted in mice together with gastric cancer myofibroblasts. Western blot and enzyme activity assays confirmed increased MMP-1, -2, and -3 activity in cancer myofibroblasts, and cancer cell migration assays indicated stimulation by MMP-1, -2, and -3 in cancer-associated myofibroblast media. Thus, cancer-derived myofibroblasts differ from their normal counterparts by increased production and activation of MMP-1, -2, and -3, and this may contribute to the remodelling of the cancer cell microenvironment. PMID:23705892

Holmberg, Christopher; Ghesquičre, Bart; Impens, Francis; Gevaert, Kris; Kumar, J Dinesh; Cash, Nicole; Kandola, Sandhir; Hegyi, Peter; Wang, Timothy C; Dockray, Graham J; Varro, Andrea

2013-06-05

197

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

2007-07-03

198

Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer.  

PubMed

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)-PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT-PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC. PMID:16331256

Aung, P P; Oue, N; Mitani, Y; Nakayama, H; Yoshida, K; Noguchi, T; Bosserhoff, A K; Yasui, W

2006-04-20

199

RECK Inhibits Stemness Gene Expression and Tumorigenicity of Gastric Cancer Cells by Suppressing ADAM-Mediated Notch1 Activation.  

PubMed

The Reversion-inducing Cysteine-rich Protein with Kazal Motifs (RECK) gene encodes a membrane-anchored glycoprotein that exhibits strong inhibitory activity against various matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase 10 (ADAM10). RECK functions as a tumor suppressor by inhibiting migration, invasion, and angiogenesis. However, whether RECK can modulate the stem-like phenotypes of cancer cells is not known. In this study, we demonstrate that RECK is down-regulated in gastric cancer cells and is further reduced in CD133-positive cancer stem-like cells. Ectopic expression of RECK induces down-regulation of the expression of stemness genes including Sox2, Oct4, and Nanog and the cancer stem cell marker CD133. Treatment of DAPT (a ?-secretase inhibitor) or TAPI-2 (a hydroxamate-based inhibitor of MMPs, tumor necrosis factor ? converting enzyme and ADAM17) reduces Notch1 shedding and activation which results in attenuation of stemness genes and CD133. Our data show that ADAM10 and ADAM17 are co-pulled down by RECK suggesting a physical interaction between RECK and ADAMs on cell surface. In addition, RECK suppresses sphere formation and sphere size of CD133-positive gastric cancer cells. Overexpression of Notch intracellular domain (NICD) or ADAM17 effectively reverse the inhibitory effect of RECK in CD133-positive cells. More importantly, RECK reduces tumorigenic activity of CD133-positive cells in vivo. Conversely, knockdown of RECK in non-tumorigenic GI2 cells increases stemness and CD133 expression and sphere forming ability. Collectively, these results indicate that RECK represses stemness gene expression and stem-like properties by inhibiting ADAM-mediated Notch1 shedding and activation. J. Cell. Physiol. 229: 191-201, 2014. © 2013 Wiley Periodicals, Inc. PMID:23881612

Hong, Kun-Jing; Wu, Deng-Chyang; Cheng, Kuang-Hung; Chen, Li-Tzong; Hung, Wen-Chun

2014-02-01

200

Gastric involvement in systemic sclerosis: a prospective study  

Microsoft Academic Search

OBJECTIVES:This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances.METHODS:Fasting and postprandial gastric electrical activity was studied in

Isabelle Marie; Hervé Levesque; Philippe Ducrotté; Philippe Denis; Marie-France Hellot; Jacques Benichou; Nicole Cailleux; Hubert Courtois

2001-01-01

201

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

202

Evaluation of anti-ulcer activity of Samanea saman (Jacq) merr bark on ethanol and stress induced gastric lesions in albino rats  

PubMed Central

Objective: To evaluate the antiulcer activity of Samanea saman (Jacq) Merr bark on ethanol and stress induced gastric lesions in albino rats. Materials and Methods: Gastric lesions were induced in rats by oral administration of absolute ethanol (5 ml/kg) and stress induced by water immersion. The antiulcer activity of methanolic extract of Samanea saman (Jacq) Merr bark (100 mg/kg, 200 mg/kg, 400 mg/kg) was compared with standard drugs. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity. Result: Samanea saman (Jacq) Merr showed a dose dependent curative ratio compared to ulcer control groups. The extract at 400 mg/kg showed significant anti ulcer activity which is almost equal to that of the standard drug in both models. The volume of acid secretion, total and free acidity was decreased and pH of the gastric juice was increased compared to ulcer control group. Conclusions: The present study indicates that Samanea saman (Jacq) Merr bark extracts have potential anti ulcer activity.

Arumugam, Suresh; Selvaraj, Senthil Velan; Velayutham, Suresh; Natesan, Senthil Kumar; Palaniswamy, Karthikeyan

2011-01-01

203

A new model of gastric bleeding induced in rats by aspirin plus clopidogrel under stimulation of acid secretion. Prophylactic effects of antiulcer drugs.  

PubMed

We set up a new model of gastric bleeding induced by the luminal perfusion of aspirin (ASA) in rats pretreated with clopidogrel under conditions where acid secretion is stimulated, and examined the effect of antiulcer drugs on the bleeding. Under urethane anesthesia, acid secretion was stimulated by i.v. infusion of histamine (8 mg/kg/h), and two catheters were inserted into the stomach, one from the esophagus and another from the duodenum. The stomach was perfused with 25 mM ASA at a rate of 0.1 ml/min using an infusion pump, and gastric bleeding was measured as hemoglobin concentration in the perfusate collected every 15 min. Clopidogrel (30 mg/kg) was given orally 24 h before the perfusion. Various antiulcer drugs were given intraduodenally 30 min before the ASA treatment. Perfusion of the stomach with ASA provoked little gastric bleeding or damage even when acid secretion was stimulated. Pretreatment with clopidogrel significantly increased the bleeding and damage caused by ASA. The bleeding and lesions produced by ASA plus clopidogrel were significantly prevented by pretreatment with famotidine and omeprazole. Mucosal protective drugs such as rebamipide, irsogladine and teprenone also prevented gastric bleeding response to ASA/clopidogrel under conditions of acid secretion, although the effect was less pronounced than that of the antisecretory drugs. We conclude that clopidogrel increases gastric bleeding induced by ASA when acid secretion is stimulated. Both antisecretory and mucosal protective drugs are effective in reducing gastric bleeding under such conditions. This model is useful for the screening of drugs that protect against gastric bleeding. PMID:22460460

Takayama, S; Izuhara, C; Yamada, N; Yamanaka, S; Hashimoto, E; Kaneko, S; Takeuchi, K

2012-02-01

204

Gastric culture  

MedlinePLUS

... gastric culture, Mycobacterium tuberculosis is diagnosed. Because these bacteria are slow growing, it may take up to 6 weeks to confirm the diagnosis. This test can also be used to detect other forms of bacteria that do not cause tuberculosis.

205

Gastric Banding  

MedlinePLUS

... and certain drugs should not have gastric banding. Surgical Procedure Before Surgery If you are considering whether ... incisions) in the abdomen. A small camera and surgical instruments are placed through the cuts into the ...

206

Nonsteroidal Anti-inflammatory Drug and Phospholipid Prodrugs: Combination Therapy With Antisecretory Agents in Rats  

Microsoft Academic Search

iting the availability of NSAIDs to interact with and See editorial on page 1145. neutralize the surface activity of intrinsic phospholipids that line the mucus gel layer of the upper GI tract. Background & Aims: The gastrointestinal side effects of Another approach advocated to reduce the GI toxic nonsteroidal anti-inflammatory drugs (NSAIDs) are re- effects of these drugs is to

LENARD M. LICHTENBERGER; CARLOS ULLOA; JIMMY J. ROMERO; AMY L. VANOUS; PAUL A. ILLICH; ELIZABETH J. DIAL

207

Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase-4 activity in obese patients with type 2 diabetes  

PubMed Central

The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass (GBP) surgery is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10-kg equivalent weight loss by GBP (n = 16) or by caloric restriction (CR, n = 14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p = 0.01), but not after CR. The increased peak glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretin concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined.

Alam, M. L.; Van der Schueren, B. J.; Ahren, B.; Wang, G. C.; Swerdlow, N. J.; Arias, S.; Bose, M.; Gorroochurn, P.; Teixeira, J.; McGinty, J.; Laferrere, B.

2013-01-01

208

Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa: relevance of MKP-1, c-fos, c-myc, and cyclin D1 expression.  

PubMed

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Our previous study demonstrated increased ERK activation and MAP kinase phosphatase-1 (MKP-1) overexpression in PHT gastric mucosa. However, it remains unknown which tyrosine kinase receptors are involved in ERK activation and whether ERK activation results in increased cell proliferation. We examined whether EGF receptor (EGF-R) is involved in ERK activation and whether ERK activation triggers epithelial proliferation in PHT gastric mucosa. In gastric mucosa of PHT and sham-operated (SO) rats we studied: (1) EGF-R mRNA and protein expression as well as phosphorylation and membrane protein tyrosine kinase (PTK) activity; (2) ERK2 phosphorylation and activity; (3) MKP-1 mRNA and protein; (4) c-fos, c-myc and cyclin D1 mRNAs, and gastric epithelial proliferation. In PHT gastric mucosa: (1) EGF-R mRNA, protein and phosphorylation and membrane PTK activity were all significantly increased by 38%, 49%, 43% and 49%, respectively; (2) ERK2 phosphorylation and activity were significantly increased by 40% and 50 %, respectively; (3) MKP-1 mRNA and protein expression were significantly increased by 27% and 34%, respectively. In contrast, (4) c-fos, c-myc, and cyclin D1 mRNAs expression were all significantly decreased in PHT gastric mucosa by 36%, 33%, and 49%, respectively, and cell proliferation was significantly lower that in SO rats (11% in PHT vs. 18% in SO). These results suggest that in PHT gastric mucosa, ERK activation is mediated through EGF-R upregulation, but the gastric epithelial proliferation is impaired, possibly by MKP-1 overexpression, leading to reduction of c-fos, c-myc and cyclin D1. PMID:11758828

Kawanaka, H; Tomikawa, M; Baatar, D; Jones, M K; Pai, R; Szabo, I L; Sugimachi, K; Sarfeh, I J; Tarnawski, A S

2001-11-01

209

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

2011-10-20

210

Host-specific differences in the physiology of acid secretion related to prostaglandins may play a role in gastric inflammation and injury.  

PubMed

Immune mediators are involved in strain-specific manifestations of Helicobacter pylori infection, and the type of immune response is associated with production of PGE(2), which in turn influences gastric acid secretion. Acid secretion plays a pivotal role, not only in the pattern of H. pylori-induced gastritis and its consequences, but also in nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathies. Mice and their transgenic modifications are widely used in Helicobacter and eicosanoid research. Using [(14)C]aminopyrine accumulation and pylorus ligation, we aimed to study acid secretion in gastric gland preparations from the commonly used strains of BALB/c and C57BL/6 mice. We found that PGE(2) does not inhibit acid secretion in gastric glands from C57BL/6 mice, in contrast to the expected antisecretory effect of PGE(2) observed in BALB/c mice. In BALB/c mice the effect of histamine and carbachol was reduced by PGE(2), whereas in C57BL/6 mice dose-response curves to these secretagogues were not affected. EP(3) receptors are not involved in acid secretion in C57BL/6 mice, as confirmed by significantly lower expression of mRNA for the EP(3) receptor. These contrary findings are important to the interpretation of the antisecretory role of eicosanoids in BALB/c and C57BL/6 mouse strains and the involvement of prostanoids in the etiology of Helicobacter-induced inflammation and NSAID-induced gastropathies. We propose that the lack of antisecretory effect of PGE(2) observed in C57BL/6 mice could reflect the extent of Helicobacter-induced inflammation and status of acid secretion in response to anti-inflammatory drugs. PMID:15677554

Padol, Ireneusz T; Hunt, Richard H

2005-01-27

211

Gastric Epithelial Stem Cells  

PubMed Central

Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide–expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells.

MILLS, JASON C.; SHIVDASANI, RAMESH A.

2013-01-01

212

Proliferative activity and malignancy in human gastric cancers. Significance of the proliferation rate and its clinical application.  

PubMed

The authors sought useful indicators for predicting the proliferative activity of human gastric cancer and attempted to evaluate its clinical significance. One hundred seventy-two patients with gastric cancer were entered in this study. All patients received bromodeoxyuridine at 200 to 1000 mg/body before laparotomy. Cell kinetics studies using the migration chase method were done for 56 patients, and the DNA synthesis time (Ts) was found to be prolonged in tumors, especially in aneuploid tumors, compared with normal mucosae. Ts correlated with bromodeoxyuridine (BrdUrd) labeling indices (LI) (r = 0.453, P less than 0.0005) and DNA indices (DI) (r = 0.534, P less than 0.0005). Thus, the DNA synthesis time was significantly prolonged in the tumors having a high S-phase fraction or DNA aneuploidy. The result of multivariate analysis indicated that LI/DI was the most potent indicator for predicting the proliferation rate (PR), which was calculated by the formula LI/Ts, and correlated significantly with PR (r = 0.863, P less than 0.0001). As was clear from the result of Cox's proportional hazard model, the predicted proliferation rate (pPR) was the most notable factor for the prognosis because pPR correlated clinically with metastasis, such as that to liver and lymph nodes. The patients with a high pPR (greater than 10%) had a worse prognosis (4-year survival rate: 16.3%) than did those with a low value (less than 10%) (4-year survival rate: 85.1%). In vitro pPR obtained by in vitro BrdUrd labeling of the specimens obtained at biopsy correlated significantly with the in vivo pPR (r = 0.960, P less than 0.0001). The authors concluded that the proliferation rate was the most important factor in judging the malignancy of human gastric cancers and that this rate should be most helpful in determining the treatment and evaluating the prognosis of individual patients. PMID:1728362

Ohyama, S; Yonemura, Y; Miyazaki, I

1992-01-15

213

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

214

Changes in cyclic AMP content of rat gastric mucosa induced by ulcerogenic stimuli--in relation to the antiulcer activity of irsogladine maleate.  

PubMed

Changes in the cyclic AMP (cAMP) content of the gastric mucosa induced by ulcerogenic stimuli were investigated in rats. Ligation of the pylorus for 5 hr produced no glandular mucosal lesion, but increased the cAMP content in the fundus and antrum. Aspirin produced glandular mucosal lesions in the pylorus-ligated rats and caused an increase of the cAMP content in the fundus and a decrease in the antrum. Irsogladine maleate (IM), an antiulcer agent, inhibited both the changes in the cAMP content and the mucosal damage induced by aspirin. IM increased the cAMP content in both regions, especially the antrum, in normal rats. Dibutyryl cAMP (dbcAMP) given orally prevented the gastric mucosal lesions induced by aspirin without affecting gastric secretion. These results suggest that 1) the changes in the cAMP content of the fundus and antrum induced by aspirin may be associated with the formation of glandular mucosal damage, 2) the antiulcer activity of IM may be related to an increase of the cAMP content in mucous cells, and 3) dbcAMP given orally may penetrate into the surface mucous cells and activate defensive functions. Thus, cAMP in the mucous cells may protect the gastric mucosa. PMID:1653374

Ueda, F; Watanabe, M; Hirata, Y; Kyoi, T; Kimura, K

1991-04-01

215

Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea.  

PubMed

Secretory diarrhea has a significant impact on morbidity and mortality worldwide and may be a predominant or minor component of pathogenesis in diarrhea of various etiologies. Crofelemer is a first-in-class antidiarrheal medication with unique inhibitory mechanisms at both the cystic fibrosis transmembrane conductance regulator and the calcium-activated chloride channels which are responsible for chloride secretion and subsequent luminal hydration. The efficacy of crofelemer has been investigated in patients with HIV-associated diarrhea, diarrhea of various infectious etiologies, as well as diarrhea-predominant irritable bowel syndrome. Crofelemer was approved by the FDA in December 2012 to treat diarrhea in HIV/AIDS patients on antiretroviral therapy. Crofelemer is not absorbed in the body and well-tolerated in small trials performed to date although long-term safety data is lacking. Crofelemer may be an important addition to the currently available drugs for the management of secretory diarrhea. PMID:23616951

Yeo, Q M; Crutchley, R; Cottreau, J; Tucker, A; Garey, K W

2013-04-01

216

Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury.  

PubMed

Oral administration to fasted rats of either absolute ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, 25% sodium chloride, or boiling water produced extensive necrosis of the gastric mucosa. Pretreatment with several prostaglandins of the A, E, or F type, either orally or subcutaneously, prevented such necrosis, and the effect was dose-dependent. This property of prostaglandins is called "cytoprotection." The protective effect against oral administration of absolute ethanol was already maximal 1 min after PGE2 given orally, and 15-30 min after PGE2 given subcutaneously. Cytoprotection by prostaglandins is unrelated to the inhibition of gastric acid secretion since, (a) it is maximal at doses that have no effect on gastric secretion, and (b) anti-secretory compounds (cimetidine, methscopolamine bromide) and antacids are not cytoprotective. Although the mechanism of gastric cytoprotection is unknown, prostaglandins appear to increase the resistance of gastric mucosal cells to the necrotizing effect of strong irritants. These results suggest that certain prostaglandins, by a mechanism other than the inhibition of gastric acid secretion, maintain the cellular integrity of the gastric mucosa, and might be beneficial in the treatment of a variety of diseases in which gastric mucosal injury is present. PMID:456839

Robert, A; Nezamis, J E; Lancaster, C; Hanchar, A J

1979-09-01

217

Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery.  

PubMed

Objective:Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment.Design:Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment.Results:As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women.Conclusion:Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.International Journal of Obesity advance online publication, 28 May 2013; doi:10.1038/ijo.2013.60. PMID:23711773

Frank, S; Wilms, B; Veit, R; Ernst, B; Thurnheer, M; Kullmann, S; Fritsche, A; Birbaumer, N; Preissl, H; Schultes, B

2013-04-29

218

Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9  

PubMed Central

Background Abberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection. Conclusion AhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.

Peng, Tie-Li; Chen, Jie; Mao, Wei; Song, Xin; Chen, Min-Hu

2009-01-01

219

[Gastric polyps].  

PubMed

Gastric polyps exist in a wide variety of types, most often benign. Endoscopic discovery of gastric polyps necessitates biopsies - not only of the lesion but also of the antral and fundic mucosa to determine the therapeutic strategy and subsequent surveillance. Fundic gland polyps are the most frequent type; they are asymptomatic with no malignant potential. They require neither treatment nor surveillance. Hyperplastic polyps, adenomas and tumors must be totally resected. Biopsies alone are insufficient to assess the extent of malignancy of adenomas and of hyperplastic polyps more than 5 mm in diameter. These polyps are associated with an elevated frequency of precancerous alterations of the gastric mucosa and consequently by an elevated risk of synchronous or metachronous cancer. Eradication of Helicobacter pylorus may reduce the risk of metachronous gastric cancer and recurrence after resection. Carcinoid tumors of the fundus most often occur in patients with hypergastrinemia during atrophic gastritis of autoimmune origin; they are not serious. The advantages and procedures for endoscopic surveillance of patients with a precancerous condition of the gastric mucosa have not yet been clearly established in populations with a low incidence of cancer. PMID:17482791

Vallot, Thierry

2007-05-07

220

The activation of proteinase-activated receptor-1 (PAR1) promotes gastric cancer cell alteration of cellular morphology related to cell motility and invasion.  

PubMed

Cell motility proceeds by cycles of edge protrusion, adhesion and retraction. Whether these functions are coordinated by biochemical or biomechanical processes is unknown. Tumor invasion and metastasis is directly related to cell motility. We showed that stimulation of proteinase-activated receptor-1 (PAR1) can trigger an array of responses that would promote tumor cell growth and invasion. Thus, we examined aspects of PAR1 activation related to cell morphological change that might contribute to cell motility. We established a PAR1 stably transfected MKN45 gastric cancer cell line (MKN45/PAR1). We examined morphological changes, Rho family activation and overexpression of cytoskeletal protein in cells exposed to PAR1 agonists (?-thrombin and TFLLR-NH2). MKN45/PAR1 grows with an elongated and polarized morphology, extending pseudopodia at the leading edge. However, in the presence of PAR1 antagonist, MKN45/PAR1 did not show any changes in cell shape upon addition of either ?-thrombin or TFLLR-NH2. Activated PAR1 induced RhoA and Rac1 phosphorylation, and subsequent overexpression of myosin IIA and filamin B which are stress fiber components that were identified by PMF analysis of peptide mass data obtained by MALDI-TOF/MS measurement. Upon stimulation of MKN45/PAR1 for 24 h with either ?-thrombin or TFLLR-NH2, the distribution of both myosin IIA and filamin B proteins shifted to being distributed throughout the cytoplasm to the membrane, with more intense luminescence signals than in the absence of stimulation. These results demonstrate that PAR1 activation induces cell morphological change associated with cell motility via Rho family activation and cytoskeletal protein overexpression, and has a critical role in gastric cancer cell invasion and metastasis. PMID:23242308

Fujimoto, Daisuke; Hirono, Yasuo; Goi, Takanori; Katayama, Kanji; Matsukawa, Shigeru; Yamaguchi, Akio

2012-12-14

221

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

2012-11-28

222

Cloning of a G-protein-coupled receptor that shows an activity to transform NIH3T3 cells and is expressed in gastric cancer cells.  

PubMed

The present study was directed towards the identification of novel factors involved in the transformation process leading to the formation of gastric cancer. A cDNA library from human gastric cancer cells was constructed using a retroviral vector. Functional cloning was performed by screening for transformation activity in transduced NIH3T3 cells. Six cDNA clones were isolated, including one encoding the elongation factor 1alpha subunit, which was already known to play a role in tumorigenesis. One cDNA (clone 56.2), which was repeatedly isolated during the course of screening, encoded a protein identical to a G-protein-coupled receptor protein, GPR35. In addition, another cDNA clone (72.3) was found to be an alternatively spliced product of the GPR35 gene, whereby 31 amino acids were added to the N-terminus of GPR35. Hence, the proteins encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively. RT-PCR experiments revealed that GPR35 gene expression is low or absent in surrounding non-cancerous regions, while both mRNAs were present in all of the gastric cancers examined. The level of 72.3-encoded mRNA was consistently significantly higher than that of 56.2 encoded mRNA. An expression pattern similar to that observed in gastric cancers was detected in normal intestinal mucosa. Based on the apparent transformation activities of the two GPR35 clones in NIH3T3 cells, and the marked up-regulation of their expression levels in cancer tissues, it is speculated that these two novel isoforms of GPR35 are involved in the course of gastric cancer formation. PMID:14965362

Okumura, Shun-ichiro; Baba, Hiroko; Kumada, Tatsuro; Nanmoku, Koji; Nakajima, Hirofumi; Nakane, Yasushi; Hioki, Koshiro; Ikenaka, Kazuhiro

2004-02-01

223

Effect of drink temperature on antropyloroduodenal motility and gastric electrical activity in humans.  

PubMed Central

There is little information on the motor mechanisms underlying the effects of meal temperature on gastric emptying. The effects on antropyloric pressures and the surface electrogastrogram of ingesting drinks at 4 degrees C, 37 degrees C, and 50 degrees C (350 ml normal saline and 50 ml low calorie (7 kj) orange cordial) given in randomised order were measured over 60 minutes in 12 normal volunteers (10 men and 2 women, aged 18-55 years). The warm and cold drinks suppressed antral pressure waves (p < 0.05), altered the organisation of antropyloric pressure waves (p < 0.05), stimulated isolated pyloric pressure waves (p < 0.05), and increased electrogastrogram frequency (p < 0.05) when compared with the 37 degrees C drink. These changes were greatest in the first 30 minutes after ingestion and greater (p < 0.05) with the 4 degrees C drink. Temperature has major effects on postprandial antropyloroduodenal motility in normal subjects. Both cold and warm drinks stimulate a pattern of motility associated with retardation of transpyloric flow.

Sun, W M; Penagini, R; Hebbard, G; Malbert, C; Jones, K L; Emery, S; Dent, J; Horowitz, M

1995-01-01

224

Antioxidant activity and ultrastructural changes in gastric cancer cell lines induced by Northeastern Thai edible folk plant extracts  

PubMed Central

Background Phytochemical products have a critical role in the drug discovery process. This promising possibility, however, necessitates the need to confirm their scientific verification before use. Hence, this study aims to evaluate (1) the antioxidant activity, (2) cytotoxicity potential, and (3) the effect on ultrastructural alteration in gastric cancer cell lines through exposure to fractions of three local Northeastern Thai edible plants. Methods Plants, Syzygium gratum, Justicia gangetica and Limnocharis flava were extracted with ethyl acetate, and each crude extract analysed for their total phenolics content by Folin-Ciocalteu method. Their antioxidant activity was assessed using the ABTS system. The extracts were then assayed for cytotoxicity on two gastric cancer cell lines Kato-III and NUGC-4, and compared with Hs27 fibroblasts as a control using the MTT assay. The cell viability (%), IC50 values, as well as the ultrastructural alterations were evaluated after treatment with one way analysis of variance (ANOVA). Results The total phenolic values of the ethyl acetate extracts were well correlated with the antioxidant capacity, with extracted product of S. gratum displaying the highest level of antioxidant activity (a 10-fold greater response) over J. gangetica and L. flava respectively. Exposure of S. gratum and J. gangetica extracts to normal cell lines (Hs27) resulted in marginal cytotoxicity effects. However, through a dose-dependent assay S. gratum and J. gangetica extracts produced cytotoxicological effects in just over 75 percent of Kato-III and NUGC-4 cell lines. In addition, apoptotic characteristic was shown under TEM in both cancer cell lines with these two extracts, whereas characteristics of autophagy was found in cell lines after post exposure to extracts from L. flava. Conclusions From these three plants, S. gratum had the highest contents of phenolic compounds and antioxidant capacity. All of them found to contain compound(s) with cytotoxicity in vitro on cancer cells but not on normal cell lines as resolved in tissue culture and ultrastructural analysis. This is the first report to show the effect on cellular alteration as apoptosis of an ethyl acetate extract of S. gratum and J. gangetica. Further studies are now focused on individual isolates and their function, prioritizing on S. gratum and J. gangetica for the development of novel therapeutics and combatants against cancer.

2013-01-01

225

Gastric axial forces in experimentally delayed and accelerated gastric emptying.  

PubMed

The aim of this study was to assess the relationship between altered axial forces and gastric emptying of solids by experimentally inhibiting or stimulating gastric axial forces by intraduodenal lipid or intravenous erythromycin, respectively. In 15 healthy volunteers, we simultaneously measured gastric emptying of solids by scintigraphy, gastroduodenal motility by manometry, and forces along the longitudinal axis of the distal stomach by an axial force transducer. When 25% of the radiolabel had emptied from the stomach, subjects (n = 5 in each group) received normal saline (controls), intraduodenal lipid, or intravenous erythromycin. The test period consisted of the infusion period (10 min) and the subsequent 30 min. Lipid significantly reduced and erythromycin increased axial forces compared with control (lipid: median 0.6 N [0-1.4 interquartile range (IQR)]; erythromycin: median 18.2 N (16.5-20.5 IQR); control: median 4.7 N (3.9-5.2 IQR); P < 0.01). Similarly, antral phasic pressure activities were different relative to control. Gastric axial forces correlated significantly with gastric emptying (Spearman rank correlation = 0.86; P < 0.01). These data are consistent with the hypothesis that axial forces affect gastric emptying of solids and suggest that measurement of axial forces provides an assessment of overall gastric propulsion during the emptying of solids. PMID:8498519

Prather, C M; Camilleri, M; Thomforde, G M; Forstrom, L A; Zinsmeister, A R

1993-05-01

226

Gastric Polyps and Protruding Type Gastric Cancer  

PubMed Central

Gastric protruding lesions are frequently encountered by health screening esophagogastroduodenoscopy. They can be classified into epithelial lesion and subepithelial lesion. Epithelial gastric lesions are generally divided into benign and malignant. Benign lesions include some types of polyps, i.e., hyperplastic polyp, fundic gland polyp, and gastric adenoma. Malignant lesions include carcinoid, early gastric cancer and advanced gastric cancer. They can be accurately diagnosed by magnifying endoscopy or narrow band imaging. Here, I will discuss benign and malignant epithelial lesions of the stomach.

2013-01-01

227

Inhibition of matrix metalloproteinase activities and tightening of tight junctions by diallyl disulfide in AGS human gastric carcinoma cells.  

PubMed

The effect of diallyl disulfide (DADS), a major component of an oil-soluble allyl sulfide garlic (Allium sativum) derivative, on the correlation between anti-invasive activity and tightening of tight junctions (TJs) was investigated in human gastric adenocarcinoma AGS cells. Our data indicated that the inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels and proteins were increased. Additionally, immunoblotting results indicated that DADS repressed the levels of claudin proteins (claudin-2, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Although further studies are needed, these results suggest that DADS treatment may inhibit tumor cell motility and invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis. PMID:22417372

Park, Hyun Soo; Kim, Gi-Young; Choi, Il-Whan; Kim, Nam Deuk; Hwang, Hye Jin; Choi, Young-Whan; Choi, Yung Hyun

2011-04-05

228

Palliative management of gastric cancer.  

PubMed

Advanced gastric cancer and its palliative treatment have a long and interesting history. Today, gastric adenocarcinoma is the second leading cause of cancer death worldwide. Unfortunately, many cases are not diagnosed until late stages of disease, which underscores the importance of the palliative treatment of gastric cancer. Palliative care is best defined as the active total care of patients whose disease is not responsive to curative treatment. Although endoscopy is the most useful method for securing the diagnosis of gastric adenocarcinoma, computed tomography may be useful to assess local and distant disease. The main indication for the institution of palliative care is the presence of advanced gastric cancer for which curative treatment is deemed inappropriate. The primary goal of palliative therapy of gastric cancer patients is to improve quality, not necessarily length, of life. Four main modalities of palliative therapy for advanced gastric cancer are discussed: resection, bypass, stenting, and chemotherapy. The choice of modality depends on a variety of factors, including individual patient prognosis and goals, and should be made on case-by-case basis. Future directions include the discovery and development of serum or stool tumor markers aimed at prevention, improving prognostication and stratification, and increasing awareness and education. PMID:17881220

Cunningham, Steven C; Schulick, Richard D

2007-09-18

229

Participation in 150 min\\/wk of moderate or higher intensity physical activity yields greater weight loss after gastric bypass surgery  

Microsoft Academic Search

BackgroundThe American College of Sports Medicine’s position stand on weight loss and prevention of weight regain in adults has suggested that overweight adults should participate in a minimum of 150 min\\/wk of moderate intensity physical activity (PA). This study compared the 3-, 6-, and 12-month postoperative weight loss between gastric bypass surgery (GBS) patients who met or exceeded the recommended

Ronald K. Evans; Dale S. Bond; Luke G. Wolfe; Jill G. Meador; Jeffrey E. Herrick; John M. Kellum; James W. Maher

2007-01-01

230

Shift of homeostasis from parenchymal regeneration to fibroblast proliferation induced by lipopolysaccharide-activated macrophages in gastric mucosal healing in vitro.  

PubMed

Wound healing in the gastrointestinal tract is an orderly process involving orchestrated responses of various cell types. Lipopolysaccharides (LPS) are major components of the outer membrane of Gram-negative bacteria, which are known to impair gastric ulcer healing in animals. The influence of LPS on intercellular communication in wound healing, however, is unknown. We examined the effects of LPS-induced macrophage activation on the proliferative response in cultured rat gastric epithelial cells (RGM-1) and fibroblasts JHU-25. Rat peritoneal resident macrophages were activated with increasing doses of LPS. The supernatant from the activated macrophage preparation, designated as macrophage-conditioned medium, was then used to treat RGM-1 or JHU-25 cells. Cell proliferation and migration were determined by [(3)H]-thymidine incorporation and a monolayer wound-healing assay, respectively. Macrophage-conditioned medium significantly suppressed RGM-1 cell proliferation but had no effect on cell migration. The same medium, however, increased JHU-25 cell proliferation. LPS treatment alone suppressed JHU-25 cell proliferation while it had no effect on RGM-1 cell proliferation, indicating that the differential effects of the macrophage-conditioned medium on cell proliferation were elicited by the factors derived from macrophages. In this regard, tumor necrosis factor (TNF)-alpha stimulated while interleukin (IL)-1beta suppressed RGM-1 cell proliferation, suggesting that IL-1beta but not TNF-alpha may play a part in the mediation of the antiproliferative effect of macrophage-conditioned medium on gastric epithelial cells. In contrast, IL-1beta suppressed while TNF-alpha had no effect on JHU-25 cell proliferation. Collectively, LPS-activated macrophages delay gastric mucosal regeneration but promote fibroblast proliferation in vitro. Such changes may partly elucidate the detrimental effect of bacterial infection on tissue repair in the stomach. PMID:17352754

Wu, William K K; Wu, William Ka Kei; Law, Priscilla T Y; Law, Priscilla Tak Yin; Wong, Helen P S; Wong, Helen Pui Shan; Lam, Emily K Y; Lam, Emily Kai Yee; Tai, Emily K K; Tai, Emily Kin Ki; Shin, Vivian Y; Shin, Vivian Yvonne; Cho, Chi H; Cho, Chi Hin

231

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

232

Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase  

Microsoft Academic Search

Background. The novel non-steroidal anti-inflammatory drug amtolmetin guacyl has been shown to possess markedly reduced ulcerogenic effects and nitric oxide-mediated gastroprotective activity against the damage induced by ethanol in the rat.Aims. To investigate, in the rat, the role of nitric oxide and of inducible nitric oxide synthase isoform in the protective effect of amtolmetin guacyl against the gastric damage induced

G. Coruzzi; G. Coppelli; S. Spaggiari; G. M. Cavestro; L. Okolicsanyi; P. Lo Giudice; C. Pisano; B. L. Tepperman

2002-01-01

233

[Participation of dopamine on the muscarinergic inhibitory effect of substance P on gastric myoelectric activity and motility].  

PubMed

Our previous study showed that microinjection of substance P (SP) into caudate nucleus inhibits gastric myoelectric fast wave and gastric motility, an effect mediated by muscarinic receptor. The present investigation showed that this effects of SP could be blocked by coinjected SP antiserum or SP antagonist [Arg6, D-Trip7,9, MePhe8]-SP6-11 or D2 dopamine antagonist haloperidol. In addition, microinjection of dopamine (DA) into caudate nucleus could also inhibit gastric fast wave and motility, an effect again being blockable by coinjected DA antagonist haloperidol or atropine. Thus, it appears that the muscarinergic inhibitory effect of SP on gastric fast wave and motility is mediated by D2 dopamine receptor. PMID:7570109

Jing, H; Lin, K W; Mei, M H

1995-06-01

234

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

2013-08-28

235

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 'ipę-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

2012-09-12

236

Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L  

Microsoft Academic Search

Rosmarinus officinalis L. crude hydroalcoholic (70%) extract was evaluated for antiulcerogenic activity employing different experimental models. The crude hydroalcoholic extract (CHE) decreased the ulcerative lesion index produced by indomethacin, ethanol and reserpine in rats. No antisecretory activity was observed on pyloric ligation model. The previous administration of l-NAME, a NO-synthase inhibitor, did not reduce the antiulcerogenic activity of CHE in

Patr??cia Corręa Dias; Mary Ann Foglio; Ana Possenti; Joăo Ernesto de Carvalho

2000-01-01

237

Active oxygen species generation by circulating leukocytes and gastric submucosal microcirculatory disturbances in the early period after thermal injury.  

PubMed

The purpose of the present study was to determine the pattern of microcirculatory disturbance to investigate the causes of gastric mucosal blood flow depression in the early period after thermal injury. Male Wistar rats were anesthetized and a 30% full skin-thickness dorsal burn was inflicted. Active oxygen species (AOS) generated by circulating leukocytes were measured by chemiluminescence. Contraction of arterioles and venules was observed by intravital microscopy, and rolling or sticking of leukocytes in venules was counted using fluorescence microscopy. AOS generation by circulating leukocytes was diminished and arteriolar contraction and increases in rolling or sticking leukocytes in venules were observed 15 min after thermal injury. Decreased AOS generation by circulating leukocytes, contractions of arterioles, and increased rolling or sticking of leukocytes in venules was observed in the early period after thermal injury. Arteriolar contraction may explain decreases in mucosal blood flow. Moreover, decreased AOS generation by circulating leukocytes does not obviate the potential participation of leukocytes in microcirculatory disturbances, because rolling or sticking leukocytes were increased significantly 15 min after thermal injury. PMID:8774997

Yoshida, M; Wakabayashi, G; Otani, Y; Oshima, A; Shimazu, M; Kubota, T; Kumai, K; Kurose, I; Miura, S; Kitajima, M

1995-01-01

238

Gastric anti-ulcer and cytoprotective effect of selenium in rats  

SciTech Connect

Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl was significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.

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

1988-01-01

239

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

240

Molecular pathogenesis of gastric cancer.  

PubMed

Gastric carcinogenesis is a complex and multifactorial process, in which infection with Helicobacter pylori plays a major role. Additionally, environmental factors as well as genetic susceptibility factors are significant players in gastric cancer (GC) etiology. Gastric cancer development results from the accumulation of multiple genetic and epigenetic changes during the lifetime of the cancer patient that will activate oncogenic and/or inactivate tumor-suppressor pathways. Numerous studies published last year provided new insights into the molecular phenotypes of GC, which will be the main focus of this review. This article also reviews the recent findings on GC tumor-suppressor genes, including putative novel genes. The understanding of the basic mechanisms that underlie gastric carcinogenesis will be of utmost importance for developing strategies of screening, early detection, and treatment of the disease, as most GC patients present with late-stage disease and have poor overall survival. PMID:24011242

Figueiredo, Ceu; Garcia-Gonzalez, Maria A; Machado, Jose C

2013-09-01

241

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

242

Gastric epithelial stem cells.  

PubMed

Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide-expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells. PMID:21144849

Mills, Jason C; Shivdasani, Ramesh A

2010-12-07

243

N-myc Downstream-regulated Gene 1 Promotes Tumor Inflammatory Angiogenesis through JNK Activation and Autocrine Loop of Interleukin-1? by Human Gastric Cancer Cells.  

PubMed

The expression of N-myc downstream-regulated gene 1 (NDRG1) was significantly correlated with tumor angiogenesis and malignant progression together with poor prognosis in gastric cancer. However, the underlying mechanism for the role of NDRG1 in the malignant progression of gastric cancer remains unknown. Here we examined whether and how NDRG1 could modulate tumor angiogenesis by human gastric cancer cells. We established NU/Cap12 and NU/Cap32 cells overexpressing NDRG1 in NUGC-3 cells, which show lower tumor angiogenesis in vivo. Compared with parental NU/Mock3, NU/Cap12, and NU/Cap32 cells: 1) induced higher tumor angiogenesis than NU/Mock3 cells accompanied by infiltration of tumor-associated macrophages in mouse dorsal air sac assay and Matrigel plug assay; 2) showed much higher expression of CXC chemokines, MMP-1, and the potent angiogenic factor VEGF-A; 3) increased the expression of the representative inflammatory cytokine, IL-1?; 4) augmented JNK phosphorylation and nuclear expression of activator protein 1 (AP-1). Further analysis demonstrated that knockdown of AP-1 (Jun and/or Fos) resulted in down-regulation of the expression of VEGF-A, CXC chemokines, and MMP-1, and also suppressed expression of IL-1? in NDRG1-overexpressing cell lines. Treatment with IL-1 receptor antagonist (IL-1ra) resulted in down-regulation of JNK and c-Jun phosphorylation, and the expression of VEGF-A, CXC chemokines, and MMP-1 in NU/Cap12 and NU/Cap32 cells. Finally, administration of IL-1ra suppressed both tumor angiogenesis and infiltration of macrophages by NU/Cap12 in vivo. Together, activation of JNK/AP-1 thus seems to promote tumor angiogenesis in relationship to NDRG1-induced inflammatory stimuli by gastric cancer cells. PMID:23846687

Murakami, Yuichi; Watari, Kosuke; Shibata, Tomohiro; Uba, Manami; Ureshino, Hiroki; Kawahara, Akihiko; Abe, Hideyuki; Izumi, Hiroto; Mukaida, Naofumi; Kuwano, Michihiko; Ono, Mayumi

2013-07-11

244

Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies.  

PubMed

Objective: To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Methods: Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. Results: In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 - 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Conclusions: Our findings do not support the notion that entericcoated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA. PMID:24040850

Hachiken, Hiroko; Murai, Ai; Wada, Kyoichi; Kuwahara, Takeshi; Hosomi, Kouichi; Takada, Mitsutaka

2013-10-01

245

Selective expression of vasoactive intestinal peptide (VIP) 2\\/pituitary adenylate cyclase-activating polypeptide (PACAP) 3 receptors in rabbit and guinea pig gastric and tenia coli smooth muscle cells  

Microsoft Academic Search

In both functional and radioligand binding studies of gastric smooth muscle from rabbit and guinea pig, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) show equal potency indicating that the receptor type is either a VIP1\\/PACAP2 or a VIP2\\/PACAP3 receptor. We have characterized the VIP\\/PACAP receptor expressed in freshly dispersed and cultured gastric and tenia coli smooth muscle

Baiqin Teng; Karnam S Murthy; John F Kuemmerle; John R Grider; Gabriel M Makhlouf

1998-01-01

246

Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells.  

PubMed

A previous study has shown that type II cGMP?dependent protein kinase (PKG II) inhibits the proliferation of gastric cancer cells through blocking EGF-triggered MAPK/ERK signal transduction, indicating that the kinase may be a potential anticancer factor. In the present study, the role of PKG II in the EGF-induced activation of transcription factors in the MAPK/ERK signal transduction pathway was investigated. BGC-823 human gastric cancer cells were infected with adenoviral constructs encoding the cDNA of PKG II (pAd?PKG II) to increase the expression of PKG II and treated with 8-pCPT?cGMP to activate the enzyme. Using luciferase reporter assays, it was revealed that PKG II markedly suppressed the EGF-induced transcriptional activities of AP-1 and Elk1. Consistent with the inhibitory effect of PKG II on AP-1 activity, the expression levels of c-Jun and c-Fos, components of AP-1, were also inhibited. Co-immunoprecipitation analysis demonstrated that EGF treatment increased the AP-1 content through inducing the formation of p-c-Jun-c-Jun homodimers and p-c-Jun-c-Fos heterodimers. However, this combination was efficiently blocked by activated PKG II. While pretreatments with MAPK inhibitors suppressed the EGF-induced transcriptional activities of AP-1 and Elk1, PKG II prevented the EGF-induced phosphorylation/activation of ERK and JNK, but not the phosphorylation of p38MAPK induced by EGF. These data suggest that PKG II inhibits the EGF-triggered proliferation of gastric cancer cells through suppressing ERK-/JNK-, but not p38MAPK, -mediated AP-1 and Elk1 transactivation. PMID:22940826

Sang, Jianrong; Chen, Yongchang; Jiang, Lu; Tao, Yan; Wu, Yan; Wang, Ying; Li, Yueying; Lan, Ting; Shao, Genbao

2012-08-27

247

Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells.  

PubMed

Sialyl-Lewis X (SLe(x)) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferases (STs). In this study we determined the capacity of ST3GAL3 and ST3GAL4 sialyltransferases to synthesize the SLe(x) antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLe(x) overexpression in cancer cell behavior both in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. The activation of tyrosine kinase receptors and their downstream molecular targets was also addressed. Our results showed that the expression of ST3GAL4 in MKN45 gastric cancer cells leads to the synthesis of SLe(x) antigens and to an increased invasive phenotype both in vitro and in the in vivo CAM model. Analysis of phosphorylation of tyrosine kinase receptors showed a specific increase in c-Met activation. The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and Src proteins and activation of Cdc42, Rac1 and RhoA GTPases. Inhibition of c-Met and Src activation abolished the observed increased cell invasive phenotype. In conclusion, the expression of ST3GAL4 leads to SLe(x) antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, in association with Src, FAK and Cdc42, Rac1 and RhoA GTPases activation. PMID:23799130

Gomes, Catarina; Osório, Hugo; Pinto, Marta Teixeira; Campos, Diana; Oliveira, Maria José; Reis, Celso A

2013-06-14

248

Expression of ST3GAL4 Leads to SLex Expression and Induces c-Met Activation and an Invasive Phenotype in Gastric Carcinoma Cells  

PubMed Central

Sialyl-Lewis X (SLex) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferases (STs). In this study we determined the capacity of ST3GAL3 and ST3GAL4 sialyltransferases to synthesize the SLex antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLex overexpression in cancer cell behavior both in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. The activation of tyrosine kinase receptors and their downstream molecular targets was also addressed. Our results showed that the expression of ST3GAL4 in MKN45 gastric cancer cells leads to the synthesis of SLex antigens and to an increased invasive phenotype both in vitro and in the in vivo CAM model. Analysis of phosphorylation of tyrosine kinase receptors showed a specific increase in c-Met activation. The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and Src proteins and activation of Cdc42, Rac1 and RhoA GTPases. Inhibition of c-Met and Src activation abolished the observed increased cell invasive phenotype. In conclusion, the expression of ST3GAL4 leads to SLex antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, in association with Src, FAK and Cdc42, Rac1 and RhoA GTPases activation.

Gomes, Catarina; Osorio, Hugo; Pinto, Marta Teixeira; Campos, Diana; Oliveira, Maria Jose; Reis, Celso A.

2013-01-01

249

Detailed measurements of gastric electrical activity and their implications on inverse solutions  

Microsoft Academic Search

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

Leo K. Cheng; G. O'Grady; Peng Du; J. U. Egbuji; J. A. Windsor; A. J. Pullan

2009-01-01

250

An unusual case of gastric outlet obstruction caused by tuberculosis: challenges in diagnosis and treatment.  

PubMed

Gastroduodenal tuberculosis (GDTB) is rare in the West. Its presentation can be non-specific and often mimics other more common conditions such as peptic ulcer disease, malignancy and Crohn's disease. Our case describes a 33-year-old Indian immigrant who presented with a 3-year history of dyspepsia and underwent balloon dilation for gastric outlet obstruction (GOO). While biopsies from the duodenum revealed only non-caseating granuloma, a high index of suspicion was maintained and colonoscopy, performed despite the absence of lower gastrointestinal symptoms, revealed a single discrete nodular and ulcerated area in the proximal transverse colon; this eventually grew Mycobacterium tuberculosis. Our patient avoided undergoing major surgery and was successfully treated with balloon dilation and antitubercular medication. We highlight the importance of having a concerted, proactive approach to diagnosis. We discuss the therapeutic challenges involving this rare condition and explain the rationale for high-dose antisecretory therapy. PMID:23704423

Padmanabhan, Hari; Rothnie, Alexander; Singh, Pradip

2013-05-22

251

Effect of some phenolic compounds and beverages on pepsin activity during simulated gastric digestion.  

PubMed

The effect of some polyphenols (resveratrol, catechin, epigallocatechin-3-gallate, and quercetin) and beverages (red wine and green tea) on the enzymatic activity of pepsin during the digestion of three different substrates (pork meat, insoluble azocasein, and denatured hemoglobin) has been investigated. The tested polyphenols and beverages increase the initial velocity of the reaction, and the activating effect is concentration dependent. The order of effectiveness of polyphenols in increasing the initial velocity of the reaction is resveratrol > or = quercetin > epigallocatechin-3-gallate > catechin. The kinetic data obtained with soluble denatured hemoglobin show that the K(m) for the substrate is not changed, whereas the V(max) of the reaction is increased. Pepsin activity follows a simple Michaelis-Menten kinetic suggesting that k(3) is increased by polyphenols. To the authors' knowledge, the present study is the first demonstration that some polyphenols and related beverages are able to enhance the enzymatic activity of pepsin. PMID:16248575

Tagliazucchi, Davide; Verzelloni, Elena; Conte, Angela

2005-11-01

252

Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats  

Microsoft Academic Search

AIM: To determine whether a specifi c adenosine A2A re- ceptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil ac- cumulation and production of pro-infl ammatory cytokines. METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg\\/kg) and HCl (0.15 mol\\/L, 8.0 mL\\/kg). 4-{3-(6-Amino-9-(5-ethylcarbamoyl-3,4- dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl)-prop-2- ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5 ?g\\/kg, IP)

Masaru Odashima; Michiro Otaka; Mario Jin; Koga Komatsu; Isao Wada; Youhei Horikawa; Tamotsu Matsuhashi; Natsumi Hatakeyama; Jinko Oyake; Reina Ohba; Sumio Watanabe; Joel Linden

2006-01-01

253

Non-steroidal anti-inflammatory drug activated gene (NAG1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drugs (NSAIDs) are powerful chemopreventive agents in various cancers. They act by inhibiting cyclooxygenase (COX) activity, or through other mechanisms. NSAID activated gene (NAG-1) has antitumorigenic and proapoptotic activities, but the mechanisms of NAG-1 induced apoptosis are poorly understood. Here we examined whether NAG-1 expression is induced in gastric

Tae Jung Jang; Hyeock Joo Kang; Jung Ran Kim; Chang Heon Yang

2004-01-01

254

Allophylus serratus: a plant with potential anti-ulcerogenic activity.  

PubMed

Allophylus serratus is known to possess various therapeutic properties. We evaluated the anti-ulcerogenic property of crude ethanolic extract of Allophylus serratus (AS) in different ulcer models in Sprague-Dawley rats. The extract at 400 mg/kg body weight, once daily, orally has a significant effect in cold restraint (CRU, 2 h cold restraint stress), aspirin (ASA, 150 mg/kg body weight, orally), alcohol (AL, 1 ml/200 gm of absolute alcohol) and pyloric ligation (PL, 4h ligation) induced gastric ulcer models as it showed protection index of 71.28, 62.50, 90.84 and 64.29% protection, respectively whereas, standard drug omeprazole (OMZ, 10mg/kg body weight) has shown protection index of 85.70, 74.99 and 74.99 in CRU, ASA and PL model respectively. Sucralfate (SUC, 500 mg/kg body weight) as a standard drug in AL model has 93.20% protection. Furthermore, AS has significantly decreased the free acidity (72.41%), total acidity (47.97%) and peptic activity (24.59%), respectively as well as has significantly increased the mucus secretion (29.41%). Conclusively the ulcer protective effect of AS may be due to its anti-secretory along with cytoprotective mechanism. PMID:15878649

Dharmani, Poonam; Mishra, Pushpesh Kumar; Maurya, Rakesh; Singh Chauhan, Vinay; Palit, Gautam

2005-07-14

255

Functional neuroimaging of gastric distention.  

PubMed

This study aimed to measure brain activation during gastric distention as a way to investigate short-term satiety. We estimated regional cerebral blood flow with positron emission tomography (15O-water) during gastric balloon inflation and deflation in 18 healthy young women. The contrast between inflated minus deflated conditions showed activation in the following four key regions that were identified a priori: dorsal brain stem; left inferior frontal gyrus; bilateral insula; and right subgenual, anterior cingulate cortex. Extant neuroimaging literature provides context for these areas as follows: the brain stem represents vagal projection zones for visceral afferent processing; the inferior frontal gyrus serves as a convergence zone for processing food-related stimuli; and both the insula and subgenual anterior cingulate cortex respond to emotional stimulation. The identification of neural correlates of gastric distention is a key step in the discovery of new treatments for obesity. New therapies could intervene by modifying the perception of gastric distention, an important contributor to meal termination and short-term satiety. This first study of brain activation during nonpainful, proximal gastric distention provides the groundwork for future research to discover novel treatments for obesity. PMID:13129550

Stephan, Elke; Pardo, José V; Faris, Patricia L; Hartman, Boyd K; Kim, Suck W; Ivanov, Emil H; Daughters, Randy S; Costello, Patricia A; Goodale, Robert L

256

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

257

Evolution of Gastric Electrical Features and Gastric Emptying in Children with Duchenne and Becker Muscular Dystrophy  

Microsoft Academic Search

OBJECTIVES:Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course.METHODS:Twenty children with MD (median age:

Osvaldo Borrelli; Gennaro Salvia; Valentina Mancini; Lucio Santoro; Francesca Tagliente; Erminia Francesca Romeo; Salvatore Cucchiara

2005-01-01

258

Amygdalofugal modulation of the vago-vagal gastric motor reflex in rat  

Microsoft Academic Search

In experiments on urethane anaesthetized rats the influence of electrical stimulation of the central nucleus of the amygdala (CNA) on gastric motility and activity of gastric-related neurons of the dorsal vagal complex was studied. Stimulation of the CNA effected spontaneous gastric motility and caused both excitatory and inhibitory changes of vagal-induced gastric relaxation. The most significant effects, mainly inhibitory, were

O. Liubashina; V. Bagaev; S. Khotiantsev

2002-01-01

259

Cholinergic effects on human gastric motility  

PubMed Central

BACKGROUND—Cholinergic regulation of chronotropic (frequency) and inotropic (force) aspects of antral contractility and how these impact on gastric emptying are not well delineated.?AIMS—To determine the effects of cholinergic stimulation and inhibition on myoelectric, contractile, and emptying parameters of gastric motility.?METHODS—Ten normal subjects underwent three studies each, using simultaneous electrogastrography (EGG), antroduodenal manometry, and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of baseline fasting manometry and EGG, subjects received saline intravenously, atropine (0.6 mg then 0.25 mg/hour intravenously), or bethanechol (5 mg subcutaneously). This was followed by another 30 minutes' recording and by three hours of postprandial recording after ingestion of a technetium-99m labelled solid meal.?RESULTS—During fasting, atropine decreased, whereas bethanechol increased, the antral manometric motility index and EGG power. Postprandially, atropine decreased the amplitude of antral contractions by DAS, decreased the postprandial antral manometric motility index, and slowed gastric emptying. Atropine caused a slight increase in postprandial frequency of antral contractions by DAS and gastric myoelectrical activity by EGG. Bethanechol slightly increased the amplitude, but slightly decreased the frequency of antral contractions by DAS and decreased the frequency of gastric myoelectrical activity by EGG, with no significant increase in the motility index or gastric emptying.?CONCLUSIONS—Cholinergic antagonism with atropine reduces antral contractility and slows gastric emptying. Cholinergic stimulation with bethanechol increases antral contractility, but decreases the frequency of antral contractions, without altering the antral motility index or gastric emptying.???Keywords: atropine; bethanechol; gastric motility; gastric scintigraphy; electrogastrography

Parkman, H; Trate, D; Knight, L; Brown, K; Maurer, A; Fisher, R

1999-01-01

260

HIV Infection in Gastric Epithelial Cells.  

PubMed

Many chronic human immunodeficiency virus (HIV) patients suffer from gastric complaints, including gastric tuberculosis and coinfection of other pathogens. Recent work has demonstrated that a variety of nonimmune cells can act as viral reservoirs, even at the early stage of HIV infection. In this study, we detect HIV viral particles, proteins, and nucleic acids in gastric epithelial cells using clinical samples. These observations are further supported by a simian immunodeficiency virus-infected macaque model. Further, the number of HIV-infected gastric epithelial cells is positively associated with blood viral load, and is negatively correlated with CD4 lymphocyte cell counts. We also demonstrate that HIV infection is accompanied by severe inflammatory response in gastric mucosa. Additionally, HIV infection activates signal transducer and activator of transcription 3 and RelA, and enhances the production of interleukin 6 and tumor necrosis factor ? in gastric epithelial cells. The present data suggest that the gastric epithelial cells are natural targets of HIV infection, and HIV infection in epithelial cells contributes to HIV-induced gastric mucosal inflammation. PMID:23852124

Liu, Rui; Huang, Lei; Li, Jingyi; Zhou, Xianzhi; Zhang, Haiyuan; Zhang, Tao; Lei, Yunlong; Wang, Kui; Xie, Na; Zheng, Yongtang; Wang, Fusheng; Nice, Edouard C; Rong, Lijun; Huang, Canhua; Wei, Yuquan

2013-07-11

261

Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett's-like metaplasia  

PubMed Central

Summary Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1? phenocopies human pathology with evolution of esophagitis, Barrett’s-like metaplasia and EAC. Histopathology and gene signatures resembled closely human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1 and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5+ gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1?-IL-6 signaling cascade and Dll1-dependent Notch signaling.

Quante, Michael; Bhagat, Govind; Abrams, Julian; Marache, Frederic; Good, Pamela; Lee, Michele D.; Lee, Yoomi; Friedman, Richard; Asfaha, Samuel; Dubeykovskaya, Zinaida; Mahmood, Umar; Figueiredo, Jose-Luiz; Kitajewski, Jan; Shawber, Carrie; Lightdale, Charles; Rustgi, Anil K.; Wang, Timothy C.

2011-01-01

262

Animal models of gastric bleeding induced by dual antiplatelet therapy using aspirin and clopidogrel - Prophylactic effect of antiulcer drugs -  

PubMed

We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y12 receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into the rat stomach, one from the esophagus and another through the pylorus via an incision in the duodenum. In the first model, the stomach was perfused with 25 mM ASA dissolved in 50 mM HCl using an infusion pump, and gastric bleeding was measured as the hemoglobin concentration in perfusate collected every 15 min. In the second model, the stomach was perfused with ASA under stimulation of acid secretion by a continuous i.v. infusion of histamine (8 mg/kg/hr). Clopidogrel (30 mg/kg) was given p.o. 24 h before the ASA perfusion, while antiulcer drugs were given i.d. or i.v. 80 min before. Perfusion of the stomach with acidified ASA or ASA under histamine-stimulated acid secretion caused minimal bleeding in the stomach with few lesions. The ulcerogenic and bleeding responses to ASA under these conditions were markedly aggravated by pretreatment with clopidogrel, which by itself provoked neither bleeding nor damage. Antiulcer drugs, such as prostaglandin E2, irsogladine, rebamipide and teprenone, reduced the severity of gastric bleeding and damage in response to ASA plus clopidogrel in the presence of both exogenous and endogenous acid. In contrast, antisecretory drugs such as a proton pump inhibitor and histamine H2 receptor antagonists markedly suppressed the gastric bleeding and lesion responses to ASA plus clopidogrel under histamine-stimulated acid secretion, but had not effect on the responses to acidified ASA plus clopidogrel. These results suggest that clopidogrel increases gastric bleeding induced by ASA and that antiulcer drugs are useful for preventing gastric bleeding caused by the dual antiplatelet therapy. PMID:23782140

Takeuchi, Koji; Izuhara, Chitose; Takayama, Shinichi; Momode, Takumi; Kojo, Masahiro; Hara, Daisuke; Amagase, Kikuko

2013-06-10

263

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

264

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

265

[Bioelectrical activity and evacuation function of the gastric stump in an early period after different means of gastric resection and variations in the formation of anastomoses].  

PubMed

The results of the stomach resection on the occasion of stomach and duodenal ulcer were analyzed. Bioelectric activity of the stomach stump was studied in a comparative aspect, and early recovery of the motor function of the resected stomach after the formation of pyloroimitating gastroduodenal anastomoses was shown. Revealed roentgenologic mechanisms of the evacuator function of the stomach stump let us determine evacuation types for the early postoperative period. The formation of pyloroimitating gastroduodenal anastomoses is functionally advantageous. PMID:14653247

Kapustin, B B; Khalimov, E V

2003-01-01

266

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

PubMed Central

BACKGROUND—In animals, activation of 5-HT1 like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones.?AIMS—To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT1 receptors, on fasting fundus tone and sensitivity to gastric distension in man.?METHODS—A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan.?RESULTS—Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased.?CONCLUSIONS—Administration of the 5-HT1 receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.???Keywords: sumatriptan; 5-HT1 receptors; gastric barostat; visceral sensitivity; enteric nervous system.

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

2000-01-01

267

Effects of histamine and activators of the cyclic AMP system on protein synthesis in and release of high molecular weight glycoproteins from isolated gastric non-parietal cells.  

PubMed Central

1. Glycoprotein and protein synthesis in and release from pig isolated, enriched gastric mucous cells were measured by the incorporation of N-acetyl-[14C]-D-glucosamine and [3H]-L-leucine, respectively, into cellular and released acid precipitable material. 2. Histamine and activators of the adenosine 3':5'-cyclic monophosphate (cyclic AMP) system maximally stimulated total protein and glycoprotein synthesis in and release from the cells at concentrations of histamine (10 microM), forskolin (10-100 microM), 3-isobutyl-1-methylxanthine (100 microM), and dibutyryl cyclic AMP (1-3 mM), respectively. In the presence of 3-isobutyl-1-methylxanthine (30 microM) histamine stimulation was enhanced. 3. As shown by gel chromatography, stimulation by histamine (100 microM), forskolin (10 microM), 3-isobutyl-1-methylxanthine (100 microM) and dibutyryl cyclic AMP (1 mM) resulted in a release of high molecular weight (approximately 2 x 10(6) daltons) glycoproteins from the cells. The histamine H2-receptor antagonist, ranitidine (100 microM), blocked the effect of histamine. 4. We conclude that cyclic AMP-dependent processes are involved in the regulation of protein and glycoprotein synthesis in and the release of high molecular weight (mucous) glycoproteins from pig gastric non-parietal cells and that histamine may be a physiological activator of this system.

Heim, H. K.; Oestmann, A.; Sewing, K. F.

1991-01-01

268

Effects of histamine and activators of the cyclic AMP system on protein synthesis in and release of high molecular weight glycoproteins from isolated gastric non-parietal cells.  

PubMed

1. Glycoprotein and protein synthesis in and release from pig isolated, enriched gastric mucous cells were measured by the incorporation of N-acetyl-[14C]-D-glucosamine and [3H]-L-leucine, respectively, into cellular and released acid precipitable material. 2. Histamine and activators of the adenosine 3':5'-cyclic monophosphate (cyclic AMP) system maximally stimulated total protein and glycoprotein synthesis in and release from the cells at concentrations of histamine (10 microM), forskolin (10-100 microM), 3-isobutyl-1-methylxanthine (100 microM), and dibutyryl cyclic AMP (1-3 mM), respectively. In the presence of 3-isobutyl-1-methylxanthine (30 microM) histamine stimulation was enhanced. 3. As shown by gel chromatography, stimulation by histamine (100 microM), forskolin (10 microM), 3-isobutyl-1-methylxanthine (100 microM) and dibutyryl cyclic AMP (1 mM) resulted in a release of high molecular weight (approximately 2 x 10(6) daltons) glycoproteins from the cells. The histamine H2-receptor antagonist, ranitidine (100 microM), blocked the effect of histamine. 4. We conclude that cyclic AMP-dependent processes are involved in the regulation of protein and glycoprotein synthesis in and the release of high molecular weight (mucous) glycoproteins from pig gastric non-parietal cells and that histamine may be a physiological activator of this system. PMID:1724626

Heim, H K; Oestmann, A; Sewing, K F

1991-10-01

269

The Helicobacter pylori Urease B Subunit Binds to CD74 on Gastric Epithelial Cells and Induces NF-?B Activation and Interleukin-8 Production  

PubMed Central

The pathogenesis associated with Helicobacter pylori infection is the result of both bacterial factors and the host response. We have previously shown that H. pylori binds to CD74 on gastric epithelial cells. In this study, we sought to identify the bacterial protein responsible for this interaction. H. pylori urease from a pool of bacterial surface proteins was found to coprecipitate with CD74. To determine how urease binds to CD74, we used recombinant urease A and B subunits. Recombinant urease B was found to bind directly to CD74 in immunoprecipitation and flow cytometry studies. By utilizing both recombinant urease subunits and urease B knockout bacteria, the urease B-CD74 interaction was shown to induce NF-?B activation and interleukin-8 (IL-8) production. This response was decreased by blocking CD74 with monoclonal antibodies. Further confirmation of the interaction of urease B with CD74 was obtained using a fibroblast cell line transfected with CD74 that also responded with NF-?B activation and IL-8 production. The binding of the H. pylori urease B subunit to CD74 expressed on gastric epithelial cells presents a novel insight into a previously unrecognized H. pylori interaction that may contribute to the proinflammatory immune response seen during infection.

Beswick, Ellen J.; Pinchuk, Irina V.; Minch, Kyle; Suarez, Giovanni; Sierra, Johanna C.; Yamaoka, Yoshio; Reyes, Victor E.

2006-01-01

270

Pectic polysaccharides of the fresh plum Prunus domestica L. isolated with a simulated gastric fluid and their anti-inflammatory and antioxidant activities.  

PubMed

A pectic polysaccharide, designated as PD, was extracted from fresh plums (Prunus domestica L.) with a simulated gastric fluid. Galacturonan, which was partially substituted with methyl and O-acetyl ester groups, and rhamnogalacturonan were the main constituents of the linear regions of the sugar chains of PD. The ramified region contained mainly 1,4-linked ?-d-galactopyranose residues and, to a lesser extent, 1,5-linked ?-l-arabinofuranose residues. The separation of PD, by DEAE-cellulose column chromatography, yielded two pectic fractions: PD-1 and PD-2, eluted with 0.1 and 0.2 M NaCl, respectively. Enzymatic digestion of PD with 1,4-?-d-polygalacturonase yielded the fraction PD-E. The parent pectin PD and the PD-1 fraction were found to diminish the adhesion of peritoneal leukocytes at the concentrations of 0.05-1.0mg/ml. However, the PD-E fraction failed to have an effect on cell adhesion at the concentrations of 0.05-0.1mg/ml. PD, PD-1 and PD-E were found to inhibit the production of superoxide anion radicals by reducing xanthine oxidase activity by 38%, 97% and 47%, respectively. Therefore, the PD-1 fraction appeared to be an active fragment of pectic macromolecule isolated from fresh plum with a simulated gastric fluid. PMID:24054219

Popov, Sergey V; Ovodova, Raisa G; Golovchenko, Victoria V; Khramova, Daria S; Markov, Pavel A; Smirnov, Vasily V; Shashkov, Alexandre S; Ovodov, Yury S

2013-07-26

271

A peptide derived from phage display library exhibits anti-tumor activity by targeting GRP78 in gastric cancer multidrug resistance cells.  

PubMed

Multidrug resistance (MDR) remains a significant challenge to the clinical treatment of gastric cancer (GC). In the present study, using a phage display approach combined with MTT assays, we screened a specific peptide GMBP1 (Gastric cancer MDR cell-specific binding peptide), ETAPLSTMLSPY, which could bind to the surface of GC MDR cells specifically and reverse their MDR phenotypes. Immunocytochemical staining showed that the potential receptor of GMBP1 was located at the membrane and cytoplasm of MDR cells. In vitro and in vivo drug sensitivity assays, FACS analysis and Western blotting confirmed that GMBP1 was able to re-sensitize MDR cells to chemical drugs. Western blotting and proteomic approaches were used to screen the receptor of GMBP1, and GRP78, a MDR-related protein, was identified as a receptor of GMBP1. This result was further supported by immunofluoresence microscopy and Western blot. Additionally, Western blotting demonstrated that pre-incubation of GMBP1 in MDR cells greatly diminished MDR1, Bcl-2 and GRP78 expression but increased the expression of Bax, whereas downregulation of GRP78, function as a receptor and directly target for GMBP1, only inhibited MDR1 expression. Our findings suggest that GMBP1 could re-sensitize GC MDR cells to a variety of chemotherapeutic agents and this role might be mediated partly through down-regulating GRP78 expression and then inhibiting MDR1 expression. These findings indicate that peptide GMBP1 likely recognizes a novel GRP78 receptor and mediates cellular activities associated with the MDR phenotype, which provides new insight into research on the management of MDR in gastric cancer cells. PMID:23792224

Kang, Jianqin; Zhao, Guohong; Lin, Tao; Tang, Shanhong; Xu, Guanghui; Hu, Sijun; Bi, Qian; Guo, Changcun; Sun, Li; Han, Shuang; Xu, Qian; Nie, Yongzhan; Wang, Biaoluo; Liang, Shuhui; Ding, Jie; Wu, Kaichun

2013-06-20

272

Gastric mucosal protection by somatostatins.  

PubMed

Somatostatin and somatostatin derivatives were tested for their ability to prevent gastric hemorrhagic erosions induced by ethanol. The somatostatin analogues were cyclohexapeptides with the rearranged amino acids 7-14 of somatostatin (S-14): Phe-Thr-Lys(Z)-Trp-Phe-D-Pro(I), Phe-Thr-Lys-Trp-Phe-D-Pro(II), Phe-Thr-Lys-D-Trp-Phe-Tyr(III) and Tyr-Phe-D-Trp-Lys-Thr-Phe(IV). In Spraque-Dawley rats receiving ethanol alone, the lesions involved 18.1 +/- 3.2% of the glandular stomach while after S- 14 (10(-7) mol/rat) the lesioned area was reduced to 6.3 +/- 1.1% (p less than 0.05). Peptide I and peptide II (doses 10(-7) -10(-9) mol/rat) decreased the area of erosions to less than 5%. Peptide III was less active and peptide IV was inactive. In rats with chronic gastric fistula S- 14 and peptide II decreased the cysteamine-stimulated acid secretion without affecting the pepsin output. We also continuously measured the intraluminal pH in the stomach of Wistar rats which develop gastric erosions after subcutaneous injection of cysteamine. The erosions were reduced by S- 14 or SMS while the intraluminal pH did not change under the influence of cysteamine or the combination of cysteamine plus S- 14 or SMS. Thus some of the peptides derived from S- 14 exert prominent gastric mucosal protection without influencing gastric secretion. PMID:2882058

Kusterer, K; Rohr, G; Schwedes, U; Usadel, K H; Szabo, S

1986-01-01

273

Gastric Cancer After Laparoscopic Adjustable Gastric Banding  

Microsoft Academic Search

A 63-year-old woman with BMI 46 underwent laparoscopic gastric banding. In the standardized follow-up after 14 and 24 months,\\u000a the GI series and gastroscopy showed no pathological signs. The patient had hematemesis 32 months after gastric banding, followed\\u000a by symptoms of obstruction, for which a laparotomy was performed. At operation, peritoneal carcinomatosis due to gastric cancer\\u000a was found. Symptoms after bariatric procedures

C. Stroh; U. Hohmann; H. Urban; Th. Manger

2008-01-01

274

Immunological and morphogenic basis of gastric mucosa atrophy and metaplasia.  

PubMed

Chronic gastritis with gastric mucosa atrophy, intestinal metaplasia and endocrine cell hyperplasia are alterations with an increased risk for the development of gastric neoplasias. Immunological studies in autoimmune gastritis, in atrophic Helicobacter pylori gastritis and in studies with transgenic mice point to a central role of the parietal cell in the development of gastric mucosa atrophy. Destruction of gastric epithelial cells alone might not be sufficient for the loss of complete gastric glands. Gastric atrophy, endocrine cell hyperplasia and intestinal and pancreatic metaplasia can be regarded as the result of altered morphogenesis within the gastric mucosa. Impaired expression of the gastric morphogenic factor Sonic Hedgehog by parietal cells and increased expression of the transcriptional activators of intestinal and pancreatic differentiation, namely CDX2 and PDX1, seem to be crucial for the development of gastric atrophy and for intestinal, endocrine and pancreatic transdifferentiation processes. Altered expression of these morphogenic factors is partly caused by changes in the gastric milieu. Further studies concerning the normal and pathological morphogenesis of the gastric mucosa and related tissues might give new insight into the pathogenesis of gastric atrophy and metaplasia. PMID:15583929

Faller, Gerhard; Kirchner, Thomas

2004-12-04

275

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

2013-07-04

276

Gastric and intestinal lactobezoars.  

PubMed

Two male full-term infants presented with unusual features of lactobezoar. One had gastric disease while the other had small bowel bezoar. The gastric lactobezoar was managed medically while the intestinal one required surgical intervention. PMID:11400808

Rao PVH; Raveenthiran, V; Dhanalakshmi, M

277

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

278

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

279

CLINICAL RESEARCH • Impaired gastric myoelectricity in patients with chronic pancreatitis: Role of maldigestion  

Microsoft Academic Search

AIM: To investigate whether gastric myoelectrical activity was impaired in patients with chronic pancreatitis (CP) and to explore the role of pancreatic enzyme in regulating gastric myoelectrical activity. METHODS: Twenty CP patients and 20 controls participated in the study. Gastric myoelectrical activity was recorded by a homemade electrogastrography (EGG) device. Two experiments were carried out. In experiment one, EGG was

Ching-Liang Lu; Chih-Yen Chen; Jiing-Chyuan Luo; Full-Young Chang; Shou-Dong Lee; Han-Chang Wu; JDZ Chen

280

Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and beta-catenin activation in gastric carcinogenesis in N-methyl-N-nitrosourea-treated K19-C2mE transgenic mice.  

PubMed

K19-C2mE transgenic (Tg) mice, simultaneously expressing cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in the gastric mucosa under the cytokeratin 19 gene promoter, were here treated with N-methyl-N-nitrosourea (MNU) and inoculated with Helicobacter pylori (H. pylori) to investigate gastric carcinogenesis. Wild-type (WT) and Tg mice undergoing MNU treatment frequently developed tumors in the pyloric region (100% and 94.7%, respectively); multiplicity in Tg was higher than that in WT (P < 0.05) with H. pylori infection. Larger pyloric tumors were more frequently observed in Tg than in WT (P < 0.05). In addition, Tg developed fundic tumors, where WT did not. No gastric tumors were observed without MNU treatment. Transcripts of TNF-alpha, iNOS, IL-1beta, and CXCL14 were up-regulated with H. pylori infection in both genotypes and were also increased more in Tg than in WT within H. pylori-inoculated animals. Immunohistochemical analysis demonstrated significantly greater beta-catenin accumulation in pyloric tumors, compared with those in the fundus (P < 0.01) with mutations of exon 3; 18.2% and 31.6% in MNU-alone and MNU + H. pylori-treated WT, whereas 21.4% and 62.5% was observed in the Tg, respectively; the latter significantly higher (P < 0.05), suggesting the role of H. pylori in Wnt activation. In conclusion, K19-C2mE mice promoted gastric cancer in both fundic and pyloric regions. Furthermore beta-catenin activation may play the important role of pyloric carcinogenesis especially in H. pylori-infected Tg. Induction of various inflammatory cytokines in addition to overexpression of COX-2/mPGES-1 could be risk factors of gastric carcinogenesis and may serve as a better gastric carcinogenesis model. PMID:19018769

Takasu, Shinji; Tsukamoto, Tetsuya; Cao, Xue-Yuan; Toyoda, Takeshi; Hirata, Akihiro; Ban, Hisayo; Yamamoto, Masami; Sakai, Hiroki; Yanai, Tokuma; Masegi, Toshiaki; Oshima, Masanobu; Tatematsu, Masae

2008-11-17

281

Activation of Intercellular Adhesion Molecule 1 Expression by Helicobacter pylori Is Regulated by NF-?B in Gastric Epithelial Cancer Cells  

PubMed Central

Interactions between leukocytes and epithelial cells may play a key role in Helicobacter pylori-associated gastric mucosal inflammation. This process is mediated by various cell adhesion molecules. The present study examined the molecular mechanisms leading to H. pylori-induced epithelial cell intercellular adhesion molecule-1 (ICAM-1; also called CD54) expression. Coculture of epithelial cells with cytotoxin-associated gene pathogenicity island-positive (cag PAI+) H. pylori strains, but not with a cag PAI? strain or H. pylori culture supernatants, resulted in upregulation of steady-state mRNA levels and cell surface expression of ICAM-1. Coculture with H. pylori induced an increase in luciferase activity in cells which were transfected with a luciferase reporter gene linked to the 5?-flanking region of the ICAM-1 gene. H. pylori activated the ICAM-1 promoter via the NF-?B binding site. An inducible nuclear protein complex bound to the ICAM-1 NF-?B site and was identified as the NF-?B p50–p65 heterodimer. H. pylori induced the degradation of I?B-?, a major cytoplasmic inhibitor of NF-?B, and stimulated the expression of I?B-? mRNA. Pretreatment of epithelial cells with pyrrolidine dithiocarbamate, which blocks NF-?B activation, inhibited H. pylori-induced ICAM-1 expression. THP-1 macrophagic cells, peripheral blood mononuclear cells, and purified neutrophils adhered to H. pylori-infected epithelial cells to a greater extent than to uninfected cells. These results show that H. pylori directly induces expression of ICAM-1 on gastric epithelial cells in an NF-?B-dependent manner that may support leukocyte attachment during inflammation.

Mori, Naoki; Wada, Akihiro; Hirayama, Toshiya; Parks, Thomas P.; Stratowa, Christian; Yamamoto, Naoki

2000-01-01

282

Effect of evening primrose oil on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats.  

PubMed

The evening primrose oil (EPO) commercially known as Callanish evening primrose oil (omega-6 polyunsaturated fatty acid) is linoleic acid (LA) and gamma-linolenic acid (GLA)-enriched oil obtained from the seeds of Oenothera biennis L. (Fam. Onagraceae). EPO was investigated for its ability to protect the gastric mucosa against injuries caused by pylorus ligation, non-steroidal anti-inflammatory drugs (NSAIDs; aspirin, indomethacin and phenylbutazone), hypothermic restraint stress and necrotizing agents [0.6 M HCl, 0.2 M NaOH, 25% NaCl or 80% (v/v) aqueous ethanol]. It was administered by gastric intubation at doses of 5 and 10 ml/kg body weight to rats fed standard chow diet. An additional group of animals was given the same amount of corn oil in each experimental model studied. The results showed that EPO at the doses of 5 and 10 ml/kg body weight provided significant protection in various experimental models used. It produced a significant inhibition of gastric mucosal damage induced by pylorus ligation, NSAIDs, or hypothermic restraint ulcers. EPO also had a marked cytoprotective effective effect against all necrotizing agents used in this study. The results suggest that EPO rich in LA and GLA possesses both antisecretory and anti-ulcerogenic effects. PMID:9350221

al-Shabanah, O A

1997-08-01

283

Effect of encapsulation of mefenamic acid with cationic Eudragit E on its bioavailability and gastric ulcerogenic activity in rabbits.  

PubMed

Encapsulation of mefenamic acid (MFA), a potent non-steroidal anti-inflammatory drug with cationic acrylic resin, Eudragit E, was carried out using a fluidized-bed granulator (Glatt AG). Three drug:polymer ratios were prepared using 50 ml of 1, 2.5 and 5 per cent w/v aqueous suspension of Eudragit to coat 100 mg powdered drug. The bioavailability of the coated and uncoated drug was studied using four groups of animals, each consisting of six male rabbits (2-2.5 kg). Investigations were performed using the rabbits to examine the effects of prolonged administration of the coated and the uncoated MFA with Eudragit E(1 and 5 per cent) in a dose of 100 mg filled in hard gelatin capsules. One capsule was given daily for 30 days. Plasma levels of MFA with Eudragit E were significantly higher than those of drug only. Meanwhile, 5 per cent w/v polymer coating afforded higher drug availability than 2.5 per cent w/v which induced a higher level than 1 per cent w/v. Chronic gastric ulcers with different severities were found in the internal mucosa of all animals. In addition, there were multiple erosions in the glandular mucosa of stomachs of rabbits receiving MFA within the treatment period. IN the control group the gastric photograph was normal in every instance. Despite the extensive morphological damage at the end of treatment, the observed changes in the stomach of rabbits given coated drug is less deleterious than that treated with uncoated drug. The results of this study indicate that the coating of MFA with cationic Eudragit E increases its bioavailability and decreases the probability of ulceration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3504500

Ramadan, E M; el-Helw, A; el-Said, Y

284

S100A8 and S100A9 promotes invasion and migration through p38 mitogen-activated protein kinase-dependent NF-?B activation in gastric cancer cells.  

PubMed

S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/ A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogenactivated protein kinase (MAPK) and nuclear factor-?B (NF-?B). The phosphorylation of p38 MAPK was not affected by the NF-?B inhibitor Bay whereas activation of NF-?B was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-?B activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-?B is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPKdependent NF-?B activation leading to an increase of MMP2 and MMP12 in gastric cancer. PMID:23456298

Kwon, Chae Hwa; Moon, Hyun Jung; Park, Hye Ji; Choi, Jin Hwa; Park, Do Youn

2013-02-26

285

Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations  

PubMed Central

Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen.

Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

2012-01-01

286

Response of gastric fundus to rectal distension in healthy persons  

Microsoft Academic Search

We aimed to record fundic motor activity in man using the barostat to ascertain if fundic motility is affected by rectal distension. The distal ends of two barostat tubes were placed in the gastric fundus and rectum in 10 healthy volunteers. The gastric bag was first inflated to a constant pressure level that recorded phasic motor activity as changes in

Jaime Zighelboim; Nicholas J. Talley; Sidney F. Phillips

1994-01-01

287

Damage to the gastric epithelium activates cellular bicarbonate secretion via SLC26A9 Cl?/HCO3? exchange  

PubMed Central

Gastric surface pH (pHo) transiently increases in response to focal epithelial damage. The sources of that increase, either from paracellular leakage of interstitial fluid or transcellular acid/base fluxes, have not been determined. Using in vivo microscopy approaches we measured pHo with Cl-NERF, tissue permeability with intravenous fluorescent-dextrans to label interstitial fluid (paracellular leakage), and gastric epithelial intracellular pH (pHi) with SNARF-5F (cellular acid/base fluxes). In response to two-photon photodamage, we found that cell-impermeant dyes entered damaged cells from luminal or tissue compartments, suggesting a possible slow transcellular, but not paracellular, route for increased permeability after damage. Regarding cytosolic acid/base status, we found that damaged cells acidified (6.63 ± 0.03) after photodamage, compared with healthy surface cells both near (7.12 ± 0.06) and far (7.07 ± 0.04) from damage (P < 0.05). This damaged cell acidification was further attenuated with 20 ?M intravenous EIPA (6.34 ± 0.05, P < 0.05) but unchanged by addition of 0.5 mM luminal H2DIDS (6.64 ± 0.08, P > 0.05). Raising luminal pH did not realkalinize damaged cells, suggesting that the mechanism of acidification is not attributable to leakiness to luminal protons. Inhibition of apical HCO3? secretion with 0.5 mM luminal H2DIDS or genetic deletion of the solute-like carrier 26A9 (SLC26A9) Cl?/HCO3? exchanger blocked the pHo increase normally observed in control animals but did not compromise repair of damaged tissue. Addition of exogenous PGE2 significantly increased pHo in wild-type, but not SLC26A9 knockout, animals, suggesting that prostaglandin-stimulated HCO3? secretion is fully mediated by SLC26A9. We conclude that cellular HCO3? secretion, likely through SLC26A9, is the dominant mechanism whereby surface pH transiently increases in response to photodamage.

Demitrack, Elise S.; Soleimani, Manoocher

2010-01-01

288

[Nutritional recommendations, supplementation, and physical activity program following Roux-en-Y gastric bypass for morbid obesity].  

PubMed

The number of gastric bypass operations (RYGB) needed worldwide is increasing annually due to the obesity epidemic.Yet the success of this treatment is only guaranteed if an appropriate exercise therapy, a corresponding change of diet, and an adequate supplementation take hold in the aftercare program.Subject to pre-existing musculoskeletal diseases, exercise therapy should start about 4 weeks after the operation and comprise alternating cardiovascular and connective tissue-restitution training. The required change of diet focuses on small portions of calorie-reduced as well as protein- and vitamin enriched food. The standard daily intake should be between 800 and 1,200 kcal. However, after RYGB, nutritive deficiencies have been registered for proteins in 1-3%, for iron in 45-52%,vitamin B12 in 33-37%, folic acid in about 35%, calcium in 10-12%, and vitamins in 10-45% of the patients. For this reason,laboratory analysis at regular intervals is necessary in the follow-up and an appropriate supplementation of minerals, vitamins,and trace elements must be implemented. PMID:20124779

Ludwig, Kaja; Bernhardt, Jörn; Schneider-Koriath, Sylke; Scharlau, Uwe; Wiessner, Reiko

2009-03-18

289

Hedgehog signaling pathway and gastric cancer.  

PubMed

Hedgehog, WNT, FGF and BMP signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis. Aberrant activation of Hedgehog signaling pathway leads to pathological consequences in a variety of human tumors, such as gastric cancer and pancreatic cancer. Endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), surgical gastrectomy and chemotherapy are therapeutic options for gastric cancer; however, prognosis of advanced gastric cancer patient is still poor. Here, Hedgehog signaling pathway in human gastric cancer and its clinical applications will be reviewed. Human SHH, IHH, DHH (Hedgehog homologs), HHAT (Hedgehog acyltransferase), HHIP (Hedgehog-interacting protein), DISP1, DISP2, DISP3 (Dispatched homologs), PTCH1, PTCH2 (Patched homologs), SMO (Smoothened homolog), KIF27, KIF7 (Costal-2 homologs), STK36 (Fused homolog), SUFU (SuFu homolog), DZIP1 (Iguana homolog), GLI1, GLI2 and GLI3 (Cubitus interruptus homologs) are implicated in the Hedgehog signaling. PTCH1, FOXM1 and CCND2 are direct transcriptional targets of Hedgehog signaling. Hedgehog signaling activation leads to cell proliferation through cell cycle regulation. SHH regulates growth and differentiation within gastric mucosa through autocrine loop and FOXL1-mediated epithelial-mesenchymal interaction. SHH is implicated in stem/progenitor cell restitution of damaged gastric mucosa during chronic infection with Helicobacter pylori. SHH up-regulation, IHH upregulation and HHIP down-regulation lead to aberrant activation of Hedgehog signaling through PTCH1 to GLI1 in gastric cancer. Small molecule compounds targeted to SMO (KADD-cyclopamine, SANT1-4, Cur61414) as well as humanized anti-SHH antibodies are potent anti-cancer drugs for gastric cancer. Cocktail of Hedgehog inhibitors would be developed as novel therapeutics for gastric cancer. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of Hedgehog signaling genes would be utilized for genetic screening of gastric cancer, while cDNA-PCR, microarray and ELISA detecting aberrant Hedgehog signaling activation would be utilized for therapeutic optional choice. Genetic screening and precise selection of therapeutic options would contribute to the realization of personalized medicine. PMID:16258256

Katoh, Yuriko; Katoh, Masaru

2005-10-18

290

Models of gastric hyperalgesia in the rat.  

PubMed

Despite the prevalence of dyspepsia, nonhuman models for study of gastric hyperalgesia are limited. We thus characterized responses to gastric distension (GD) in the absence of and after two different gastric insults. A balloon was surgically placed into the stomach, and electromyographic responses to GD were recorded from the acromiotrapezius muscle at various times after balloon placement. Rats received either 20% acetic acid (HAc) or saline injections into the stomach wall or 0.1% iodoacetamide (IA) in drinking water. Responses to GD were monotonic with increasing distending pressure (10-80 mmHg) and were reproducible from days 3-14 after balloon implantation. Both HAc injection and IA ingestion led to increased responses to GD (i.e., gastric hyperalgesia), which, in the case of HAc, persisted for 60 days after HAc treatment. HAc injection produced ulcers in all treated animals; IA ingestion produced no lesions. Myeloperoxidase activity significantly increased after HAc but not saline injection or IA ingestion. In the awake, unrestrained rat, visceromotor responses to GD are quantifiable, reliable, and reproducible. Significantly enhanced responses to GD were apparent in two models of gastric insult, both of which may be useful for the study of the mechanisms of gastric hyperalgesia. PMID:12181181

Ozaki, Noriyuki; Bielefeldt, Klaus; Sengupta, J N; Gebhart, G F

2002-09-01

291

Antidiabetic and antiulcer effects of extract of Eugenia jambolana seed in mild diabetic rats: study on gastric mucosal offensive acid-pepsin secretion.  

PubMed

Diabetes has been reported to increase propensity to peptic ulceration through its effect both on offensive and defensive mucosal factors. Seeds of Eugenia jambolana (EJ) have been reported to have both antidiabetic as well as ulcer protective effects. The present study evaluates the antidiabetic effects of ethanolic extract of dried seed kernel of Eugenia jambolana (EJE) and its comparative effect on gastric ulceration and acid-pepsin secretion with standard antisecretory FL-blocker. Ranitidine and antidiabetic glibenclamide with a premise that Eugenia jambolana may show better ulcer healing effects by promoting defensive or reducing offensive mucosal factors in mild diabetes (MD) rats. MD was produced in adult rats by administration of streptozotocin (45 mg/kg, ip). EJE was given orally in the doses of 100-400 mg/kg for 10 days and in the dose of 200 mg/kg for 30 days respectively to study its dose- and time-dependent effects on various diabetic parameters like blood glucose, serum cholesterol and triglycerides, insulin level and glycosylated hemoglobin. For ulcer protective and gastric secretion studies, EJE (200 mg/kg) was given orally for 10 days against 2 h cold restraint stress (CRS)-, 4 h pylorus ligation (PL), aspirin (ASP, 200 mg/kg, 4 h)--and 95% ethanol (EtOH, 1 ml/200 g, 1 h)-induced gastric ulcers and offensive acid-pepsin secretion after 4 h PL with co-occurring MD in rats. EJE showed dose-dependent decrease in blood glucose level in MD rats. Blood glucose level remained stable in mild diabetic rats from 3rd day onwards after streptozotocin administration (taken as 1st day for treatment) and EJE (200 mg/kg) showed anti-hyperglycemic effect on 10th day of its administration. Further, EJE in the above dose also decreased cholesterol level with little or no effect on triglycerides level and reversed the decrease and increase in insulin and glycosylated hemoglobin level near to the normal level as observed alter 30 days treatment in MD rats. MD rats exhibited an increased propensity to gastric ulceration induced by CRS, ASP, EtOH and PL and caused increase in acid-pepsin secretion. EJE was not only effective in reversing the increased propensity to ulceration in diabetic rats but also decreased the acid-pepsin output better than glibenclamide. The ulcer protective effect of Eugenia jambolana seems to be due to its antidiabetic and gastric antisecretory effects. PMID:20112817

Chaturvedi, Aditi; Bhawani, G; Agarwal, P K; Goel, Shalini; Singh, A; Goel, R K

292

Gastric Lipase Secretion in Children with Gastritis  

PubMed Central

Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

Tomasik, Przemyslaw J.; Wedrychowicz, Andrzej; Rogatko, Iwona; Zajac, Andrzej; Fyderek, Krzysztof; Sztefko, Krystyna

2013-01-01

293

Gastric lipase secretion in children with gastritis.  

PubMed

Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis. PMID:23899880

Tomasik, Przemyslaw J; W?drychowicz, Andrzej; Rogatko, Iwona; Zaj?c, Andrzej; Fyderek, Krzysztof; Sztefko, Krystyna

2013-07-29

294

Effect of Electrical Stimulation on Acupuncture Points in Diabetic Patients with Gastric Dysrhythmia: A Pilot Study  

Microsoft Academic Search

Background\\/Aims: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. Methods: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months

Chi-Sen Chang; Chung-Wang Ko; Chun-Ying Wu; Gran-Hum Chen

2001-01-01

295

Rebamipide Reduces Recurrence of Experimental Gastric Ulcers: Role of Free Radicals and Neutrophils  

Microsoft Academic Search

Mucosal inflammation is a crucial factor for the recurrence of peptic ulcer. In this study, we examined the effect of rebamipide on neutrophils infiltration, lipid peroxidation, and antioxidative enzyme activities in the recurrence of experimental gastric ulcer. Ulcer recurrence was examined at 60, 100, and 140 days after production of acetic acid-induced gastric ulcers in rats. Gastric neutrophil infiltration, lipid

Kazushi Sakurai; Toshihiro Osaka; Katsuya Yamasaki

2005-01-01

296

Treatment of gastric carcinoids.  

PubMed

Gastric carcinoid tumors are uncommon, but their percentage among all gastric malignancies has increased to 1.8%. Although they are most often discovered incidentally during endoscopy, gastric carcinoids can present with abdominal pain, bleeding, or symptoms related to the secretion of bioactive substances, most commonly histamine. Gastric carcinoids originate from the foregut and are derived from histamine-containing enterochromaffin-like (ECL) cells. Type I gastric carcinoid, the most common, exhibits slow growth and benign behavior. It occurs within the setting of chronic atrophic gastritis with achlorhydria-induced hypergastrinemia. Gastrin acts directly on ECL cells to induce hyperplasia, dysplasia, and, eventually, neoplasia. Type II gastric carcinoid, the least common type, occurs in patients with gastrinoma-associated multiple endocrine neoplasia syndrome-type 1 (MEN-1). The overall survival is related more to the underlying MEN-1 syndrome than to the gastric carcinoid. Rodents readily develop gastric carcinoid tumors in response to hypergastrinemia. However, in humans, other factors in addition to hypergastrinemia, such as pernicious anemia or MEN-1, must be present, implying that a genetic predisposition is necessary for the development of these tumors. Type III or sporadic gastric carcinoids exhibit a more malignant behavior, with overall 5-year survival rates of less than 50% and normal serum gastrin concentrations. Treatment of all types of gastric carcinoids is predicated upon accurate classification and staging. Radiolabeled somatostatin analogues are superior to conventional radiologic imaging techniques in detecting both primary and metastatic lesions. Treatment of choice for localized disease is excision, either endoscopically or surgically. Antrectomy, by eliminating the trophic effect of gastrin, can be useful for select type I carcinoids. Long-acting somatostatin analogues are excellent palliative agents. PMID:17391627

Hou, Wei; Schubert, Mitchell L

2007-04-01

297

Acute Gastric Dilatation Resulting in Gastric Emphysema Following Postpartum Hemorrhage  

PubMed Central

Acute gastric dilatation is a rare entity, with varying aetiologies the majority of which are benign. Delay in diagnosis and treatment could result in sequelae such as gastric emphysema (pneumatosis), emphysematous gastritis, gangrene, and perforation. Gastric emphysema as a result of a benign nongangrenous condition such as gastroparesis, adynamic ileus can be successfully managed conservatively. Here, we present an interesting case of acute gastric dilatation resulting in gastric emphysema following massive postpartum hemorrhage.

Khan, Suhail Aslam; Boko, Edmond; Khookhar, Haseeb Anwar; Woods, Sheila; Nasr, A. H.

2012-01-01

298

Gastric Necrosis due to Acute Massive Gastric Dilatation  

PubMed Central

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

299

Prevalence of gastric ulcers in endurance horses – a preliminary report  

Microsoft Academic Search

Gastric endoscopy was performed at the end of a 50 or 80 km endurance ride. Gastric ulceration was evident in 67% of the horses with ulcers on the squamous region of the stomach found in 57% of the horses and active bleeding of the glandular mucosa in 27%. Three horses (10%) had lesions only on the glandular mucosa. Values of

Jorge E Nieto; Jack R Snyder; Pablo Beldomenico; Monica Aleman; James W Kerr; Sharon J Spier

2004-01-01

300

The prevalence of gastric ulceration in racehorses in New Zealand  

Microsoft Academic Search

AIM: To establish the prevalence and factors influencing the prevalence and severity of gastric ulceration in racehorses in New Zealand.METHODS: Horses (n=171) in active training for racing by trainers (n=24) located throughout New Zealand were examined using gastroscopy during 2003 and 2004. Images of the examination were recorded and reviewed, and an ordinal grade based on the severity of gastric

RJW Bell; TD Mogg; NR Perkins

2007-01-01

301

Patient motion artifacts on scintigraphic gastric emptying studies  

SciTech Connect

Patient motion during scintigraphic gastric emptying studies can result in the false diagnosis of gastroesophageal reflux or of accelerated gastric emptying. A simple means of detecting patient motion, by generating a time-activity curve from a region of interest drawn about a Tc-99m marker, is described.

Glowniak, J.V.; Wahl, R.L.

1985-02-01

302

Calcium, carbonic anhydrase and gastric acid secretion.  

PubMed

Previous data concerning the action of calcium (Ca) on gastric acid secretion (GAS) indicated that calcium ions increase GAS elicited by gastrin released through a vagal mechanism, and also by a direct effect on parietal cells. Our research showed that the stimulating effect of calcium on gastric acid secretion can be antagonized by verapamil administration, which reduces gastric acid secretion . In the present study we followed the effect induced by administration of calcium and Ca-chelating agents (disodium EDTA) on gastric acid secretion and on carbonic anhydrase (CA) activity. We selected two groups of healthy volunteers: Group I (n=21) received a single i.v. dose of CaCl2 (15 mg/kg b.w.), whereas Group II (n=22) received a single i.v. dose of disodium EDTA (5 mg/kg b.w.). We determined blood calcium before and after treatment, gastric acid secretion at 2 hours. erythrocyte CA II activity, and CA IV activity in membrane parietal cells, which were isolated from gastric mucosa obtained by endoscopic biopsy. Assessment of carbonic anhydrase activity was achieved by the stopped-flow method. In Group I calcium administration increased blood calcium, HCl output, CA II and CA IV activity as compared to initial values. In Group II, disodium EDTA reduced blood calcium, HCl output, CA II and CA IV activity as compared to initial values. The results demonstrated that increased blood calcium and GAS values after calcium administration correlated with the increase of erythrocyte CA II and parietal cell CA IV activity, while disodium EDTA induced a reversed process. Our results also show that cytosolic CA II and membrane CA IV values are sensitive to calcium changes and they directly depend on these levels. Our data suggest that intra- and extracellular pH changes induced by carbonic anhydrase might account for the modulation of the physiological and pathological secretory processes in the organism. PMID:11551141

Puscas, I; Coltau, M; Baican, M; Domuta, G; Hecht, A

2001-01-01

303

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

304

Gastric pneumatosis in infancy.  

PubMed Central

Gastric pneumatosis (gas in the wall of the stomach) is an uncommon but characteristic plain-film radiographic sign. In infancy it is associated either with gastric outlet obstruction, usually hypertrophic pyloric stenosis, or necrotizing gastroenterocolitis. Differential diagnosis is mainly based on associated clinical findings, as exemplified by the 2 cases reported here. Both infants had isolated gastric pneumatosis as the principal radiographic finding. Correct diagnosis was greatly aided by recognition of this x-ray sign so that appropriate therapy was started without delay. Images Fig. 1. Fig. 2.

Leonidas, J C

1976-01-01

305

Rapid Gastric Emptying  

MedlinePLUS

... result of stomach surgery such as fundoplication or gastric bypass. The condition is also seen in people with ... distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about ...

306

Occupation and gastric cancer.  

PubMed

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. PMID:12782770

Raj, A; Mayberry, J F; Podas, T

2003-05-01

307

H. pylori acutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion.  

PubMed

Acute Helicobacter pylori infection produces hypochlorhydria. The decrease in acid facilitates survival of the bacterium and its colonization of the stomach. The present study was designed to identify the pathways in oxyntic mucosa by which acute H. pylori infection inhibits acid secretion. In rat fundic sheets in an Ussing chamber, perfusion of the luminal surface with H. pylori in spent broth (10(3)-10(8) cfu/ml) or spent broth alone (1:10(5) to 1:10(0) final dilution) caused a concentration-dependent increase in somatostatin (SST; maximal: 200 ± 20 and 194 ± 9% above basal; P < 0.001) and decrease in histamine secretion (maximal: 45 ± 5 and 48 ± 2% below basal; P < 0.001); the latter was abolished by SST antibody, implying that changes in histamine secretion reflected changes in SST secretion. Both responses were abolished by the axonal blocker tetrodotoxin (TTX), the sensory neurotoxin capsaicin, or the CGRP antagonist CGRP8-37, implying that the reciprocal changes in SST and histamine secretion were due to release of CGRP from sensory neurons. In isolated rabbit oxyntic glands, H. pylori inhibited basal and histamine-stimulated acid secretion in a concentration-dependent manner; the responses were not affected by TTX or SST antibody, implying that H. pylori can directly inhibit parietal cell function. In conclusion, acute administration of H. pylori is capable of inhibiting acid secretion directly as well as indirectly by activating intramural CGRP sensory neurons coupled to stimulation of SST and inhibition of histamine secretion. Activation of neural pathways provides one explanation as to how initial patchy colonization of the superficial gastric mucosa by H. pylori can acutely inhibit acid secretion. PMID:23392237

Zaki, Muhammad; Coudron, Philip E; McCuen, Robert W; Harrington, Leslie; Chu, Shijian; Schubert, Mitchell L

2013-02-07

308

Parenteral Adjuvant Activities of Escherichia coli Heat-Labile Toxin and Its B Subunit for Immunization of Mice against Gastric Helicobacter pylori Infection  

PubMed Central

The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric challenge with H. pylori. Control mice were immunized orally with urease plus LT, a regimen shown previously to protect against H. pylori gastric infection. Parenteral immunization using either LT or LTB as adjuvant protected mice against H. pylori challenge as effectively as oral immunization and enhanced urease-specific immunoglobulin G (IgG) responses in serum as effectively as aluminum hydroxide adjuvant. LT and LTB had adjuvant activity at subtoxic doses and induced more consistent antibody responses than those observed with oral immunization. A mixture of a low dose of LT and a high dose of LTB stimulated the highest levels of protection and specific IgG in serum. Urease-specific IgG1 and IgG2a antibody subclass responses were stimulated by all immunization regimens tested, but relative levels were dependent on the adjuvant used. Compared to parenteral immunization with urease alone, LT preferentially enhanced IgG1, while LTB or the LT-LTB mixture preferentially enhanced IgG2a. Parenteral immunization using LT or LTB as adjuvant also induced IgA to urease in the saliva of some mice. These results show that LT and LTB stimulate qualitatively different humoral immune responses to urease but are both effective parenteral adjuvants for immunization of mice against H. pylori infection.

Weltzin, Richard; Guy, Bruno; Thomas, William D.; Giannasca, Paul J.; Monath, Thomas P.

2000-01-01

309

Capsaicin and Gastric Ulcers  

Microsoft Academic Search

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

M. N. Satyanarayana

2006-01-01

310

Localization of gastric peroxidase and its inhibition by mercaptomethylimidazole, an inducer of gastric acid secretion.  

PubMed Central

Mercaptomethylimidazole (MMI) is a potent inducer of gastric acid secretion which is associated with significant inhibition of peroxidase activity of rat gastric mucosa in vivo. A time-dependent increase in acid secretion correlates well with time-dependent decrease in the peroxidase activity. In a chamber experiment in vitro using isolated gastric mucosa, MMI stimulates acid secretion, showing an almost linear response up to 600 microM. The time-dependent increase in acid secretion is also correlated with time-dependent inhibition of the peroxidase activity. This effect is not mediated through oxidation of MMI by flavin-containing mono-oxygenase, which is absent from gastric mucosa. The peroxidase has been localized mainly in parietal cells isolated and purified from gastric mucosa by controlled digestion with collagenase followed by Percoll-density-gradient centrifugation. Peroxidase activity was further localized in the outer membrane of the purified mitochondria of the parietal cell by some membrane-impermeant reagents, indicating outward orientation of the enzyme. MMI can inhibit the peroxidase activity of both the parietal cell and its mitochondria in a concentration-dependent manner. The possible involvement of the parietal-cell peroxidase-H2O2 system in MMI-induced acid secretion may be suggested.

Bandyopadhyay, U; Bhattacharyya, D K; Chatterjee, R; Banerjee, R K

1992-01-01

311

Experimental gastric cancer.  

PubMed

Since Sugimura and Fujimura (1967) succeeded in selectively inducing gastric carcinomas in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (1), similar models for the induction of gastric carcinomas in other species by using MNNG and its ethyl derivative N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) have been established. The susceptibility to gastric carcinogenesis, the histologic types of gastric carcinomas induced, and their biological behavior depend on the mode of treatment, species, strain and/or sex. The organ specificity of MNNG correlates well with the level of DNA methylation in target and non-target tissues following oral administration in rats. The high concentration of methylated DNA bases in the stomach mucosa appears to result from thiol-mediated acceleration of the decomposition of MNNG. Experimental gastric carcinogenesis is markedly modified by various factors and agents, including bile reflux, bile acids, sodium chloride, and ulceration, indicating that both host and environmental factors contribute significantly to gastric carcinogenesis by chemical carcinogens. PMID:1742532

Ohgaki, H; Kleihues, P; Sugimura, T

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

The Relationship Between Gastric Myoelectric Activity and SCN5A Mutation Suggesting Sodium Channelopathy in Patients With Brugada Syndrome and Functional Dyspepsia - A Pilot Study  

PubMed Central

Background/Aims SCN5A encodes the cardiac-specific NaV1.5 sodium channel, and Brugada syndrome is a cardiac conduction disorder associated with sodium channel ?-subunit (SCN5A) mutation. The SCN5A-encoded NaV1.5 channel is also found on gastrointestinal smooth muscle and interstitial cells of Cajal. We investigated the relationship between functional dyspepsia (FD) and SCN5A mutation to evaluate sodium channelopathy in FD. Methods Patients with Brugada syndrome or FD were examined using upper endoscopy, electrogastrography (EGG), FD symptom questionnaire based on Rome III criteria and genetic testing for SCN5A mutation. Symptom scores of FD and EGG findings were analyzed according to SCN5A mutation. Results A total of 17 patients (4 Brugada syndrome and 13 FD) participated in the study. An SCN5A mutation was noted in 75.0% of the patients with Brugada syndrome and in 1 (7.7%) of the patients with FD. Of 4 patients with SCN5A mutation, 2 (50%) had FD. Postprandial tachygastria and bradygastria were noted in 2 (50%) and 1 (25%) of the patients with SCN5A mutation, respectively. The EGG findings were not significantly different between positive and negative mutation in 17 patients. Conclusions Although we did not find statistically significant results, we suggest that it is meaningful to attempt to identify differences in symptoms and gastric myoelectric activity according to the presence of an SCN5A mutation by EGG analysis. The relationship between FD and sodium channelopathy should be elucidated in the future by a large-scale study.

Jung, Kyo Tae; Kim, Jie-Hyun; Shin, Dong-Jik; Joung, Bo Young; Lee, Moon-Hyoung; Jang, Yang Soo

2012-01-01

314

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

315

Electrogastrography: a non-invasive measurement of gastric function  

Microsoft Academic Search

Background  Electrogastrography (EGG) is the non-invasive measurement of gastric electrical activity. With the development of modern technology,\\u000a improved recording and automated analysis, it is a reliable and accurate technique for the measurement of gastric myoelectrical\\u000a activity providing information about the frequency and regularity of the gastric slow wave.\\u000a \\u000a \\u000a \\u000a Aim  The aim of this report is to evaluate its role in clinical practice.

P. M. Lawlor; J. A. McCullough; P. J. Byrne; J. V. Reynolds

2001-01-01

316

Antisecretory activity from the flowers of Chiranthodendron pentadactylon and its flavonoids on intestinal fluid accumulation induced by Vibrio cholerae toxin in rats  

Microsoft Academic Search

Ethnopharmacological relevanceThe flowers of Chiranthodendron pentadactylon Larreat. (Sterculiaceae) has been traditionally used as folk medicine in Mexico for the treatment of gastrointestinal disorders such as diarrhea and dysentery.

Claudia Velázquez; Fernando Calzada; Baldomero Esquivel; Elizabeth Barbosa; Samuel Calzada

2009-01-01

317

A review on gastric diverticulum  

PubMed Central

The gastric fundal diverticulae are rare. They can present with variable symptoms. We are enclosing a literature review on gastric fundal diverticulum. Lessons have emerged which may help in the management of this rare condition in future.

2012-01-01

318

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

319

Coleusin factor exerts cytotoxic activity by inducing G 0\\/G 1 cell cycle arrest and apoptosis in human gastric cancer BGC823 cells  

Microsoft Academic Search

Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our previous studies have demonstrated that CF significantly inhibits growth in some kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing

Bo Sun; Shuo Geng; Xiaojia Huang; Jin Zhu; Shu Liu; Yajing Zhang; Jian Ye; Yongjin Li; Jingze Wang

2011-01-01

320

The Helicobacter pylori Urease B Subunit Binds to CD74 on Gastric Epithelial Cells and Induces NF B Activation and Interleukin8 Production  

Microsoft Academic Search

The pathogenesis associated with Helicobacter pylori infection is the result of both bacterial factors and the host response. We have previously shown that H. pylori binds to CD74 on gastric epithelial cells. In this study, we sought to identify the bacterial protein responsible for this interaction. H. pylori urease from a pool of bacterial surface proteins was found to coprecipitate

Ellen J. Beswick; Irina V. Pinchuk; Kyle Minch; Giovanni Suarez; Johanna C. Sierra; Yoshio Yamaoka; Victor E. Reyes

2006-01-01

321

Helicobacter pylori and gastric cancer  

Microsoft Academic Search

Helicobacter pylori is now well known as an important pathogen related to the development of gastric cancer. However, some clinicians still doubt\\u000a the causal association of H. pylori with the development of gastric cancer. To summarize the recent clinical data on the link between H. pylori and gastric cancer, we reviewed related articles published over the past 3 years, after

Hidekazu Suzuki; Eisuke Iwasaki; Toshifumi Hibi

2009-01-01

322

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

323

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.  

PubMed

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. PMID:17214962

Yasuda, Hiroshi; Hirata, Shuko; Inoue, Kazuaki; Mashima, Hirosato; Ohnishi, Hirohide; Yoshiba, Makoto

2006-12-29

324

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

325

Regulation of Gastric Nesfatin-1/NUCB2.  

PubMed

Originally identified in the hypothalamus as a satiety factor, recent studies provide evidence that nefatin-1/NUCB2 is a gut-brain peptide with a broader array of actions. Detection of abundant nesfatin-1/NUCB2 in gastric X/A like endocrine cells, which also produce the orexigenic hormone ghrelin, indicates that gastric mucosa may be one of the predominant sources of nesfatin-1/NUCB2. Functional studies have revealed significant effects of nefatin-1 on inhibition of feeding behavior and on glucose homeostasis. These metabolic functions make nesfatin-1/NUCB2 a novel candidate for treatment of obesity and diabetes. However, deficiencies in our understanding of nesfatin-1/NUCB2 receptor pose a significant hurdle for therapies that target its action. Defining novel pathways to alter the production of nesfatin-1/NUCB2 would shift therapeutic focus to gastric targets. A necessary precondition is improved understanding of the mechanisms by which nesfatin-1/NUCB2 is synthesized and secreted by gastric X/A like cells. Recent studies provides evidence that mTOR is a critical regulatory molecule in these endocrine cells and that its activity is linked to the production of ghrelin and nesfatin-1/NUCB2. These findings suggest that gastric mTOR is involved in the regulation of food intake and overall energy metabolism through modulation of ghrelin and nesfatin-1/NUCB2. In this review, we first summarize current advances in the relationship between organism energy status and nesfatin-1/NUCB2 levels, and then discuss the novel finding on mTOR as the gastric fuel sensor and its role in the regulation of nesfatin-1/NUCB2 expression. PMID:23537086

Li, Ziru; Mulholland, Michael; Zhang, Weizhen

2013-03-25

326

Diverse proteomic alterations in gastric adenocarcinoma.  

PubMed

Gastric adenocarcinoma is one of the most common cancers in Asian countries including China. Although its incidence rates in the West are lower than that in Asia, gastric cancer is still a major health problem worldwide, being second only to lung cancers in the number of deaths it causes. Helicobacter pylori infection has been identified as the major pathogen, but the detailed pathogenesis of gastric carcinoma remains elusive. Due to the lack of suitable and specific biomarkers for early detection, most cases of the disease are diagnosed at late stages and the survival rate is low. In this study, we used a proteomic approach to globally analyze the protein profiles of paired surgical specimens of primary gastric adenocarcinoma and nontumor mucosa aiming at identifying specific disease-associated proteins as potential clinical biomarkers and for carcinogenetic study. Compared to nontumor tissues, multiple protein alterations were found in tumor tissues. Some of these alterations involve variations in the expression of cytoskeleton proteins, including an increase in cytokeratin 8 and tropomyosin isoform and a decrease in cytokeratin 20. Co-up-regulations of heat-shock proteins and glycolytic enzymes were observed in tumor tissues, indicating self-protective efforts of cells and the growing energy requirement during malignant transformation. Diverse regulations also occurred with proteins involved in cell proliferation and differentiation, such as GMP reductase 2 and creatine kinase B, and proteins bearing potential tumor suppressor activities, including prohibitin and selenium binding protein 1. More interestingly, a human stomach-specific protein, 18 kDa antrum mucosa protein, was found to be dramatically under-expressed in cancer tissues, implicating a possible special pathological role for this protein in gastric carcinogenesis. Further comprehensive evaluation by globally considering the altered factors may result in the discovery of a biomarker index for effective assessment of the disease and may provide in-depth information for better understanding the pathogenesis of gastric cancer. PMID:15378696

He, Qing-Ye; Cheung, Yim Hing; Leung, Suet Yi; Yuen, Siu Tsan; Chu, Kent-Man; Chiu, Jen-Fu

2004-10-01

327

Helicobacter pylori Induced Oxidative Stress and DNA Damage in a Primary Culture of Human Gastric Mucosal Cells  

Microsoft Academic Search

Helicobacter pylori has been identified in the pathogenesis of chronic active gastritis and peptic ulcer disease and is epidemiologically linked to gastric cancer and lymphoma. Our previous studies have demonstrated enhanced production of reactive oxygen species (ROS) in cultured gastric adenocarcinoma cells (ATCC CRL\\/1739) in association with H. pylori. Recently, we have isolated and cultured normal human gastric mucosal cells

Debasis Bagchi; Thomas R. McGinn; Xumein Ye; Manashi Bagchi; Roger L. Krohn; Archana Chatterjee; Sidney J. Stohs

2002-01-01

328

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

329

Enzymatic sulfation of mucus glycoprotein in gastric mucosa  

SciTech Connect

Among the posttranslational modifications that mucus glycoprotein undergo prior to secretion into the gastric lumen is the process of sulfation of the carbohydrate chains. These sulfate groups impart strongly negative charge to nucus glycoprotein and are thought to play a major role in the maintenance of gastric mucosal integrity. The authors report here the presence and some properties of an enzyme involved in the sulfation of gastric mucus glycoprotein. The sulfotransferase activity which catalyzes the transfer of sulfate ester group from PAPS to mucus glycoprotein was located in the detergent extracts of the microsomal fraction of rat gastric mucosa. Optimum enzymatic activity for sulfation of gastric mucin was obtained using 0.5% Triton X-100 and 25mM NaF at a pH of 6.8. ATP, ADP, MgCl/sub 2/ and MnCl/sub 2/ at concentrations examined were inhibitory. Under optimal conditions, the rate of sulfate incorporation was proportional to the microsomal enzyme protein concentration up to 50..mu..g and remained constant with time of incubation for at least 1h. The apparent Km value of the enzyme for gastric mucus glycoprotein was 8.3 x 10/sup -6/M. The /sup 35/S-labeled product of the enzyme reaction cochromatographed on Bio-Gel A-50 with gastric mucin, and gave on CsCl equilibrium density gradient centrifugation a band at the density of 1.48 in which the /sup 35/S label coincided with the glycoprotein.

Liau, Y.H.; Carter, S.R.; Gwozdzinski, K.; Nadziejko, C.; Slomiany, A.; Slomiany, B.L.

1986-05-01

330

Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats.  

PubMed Central

1. Experiments were performed on chloralose-urethane anaesthetized rats to determine the involvement of extrinsic gastric autonomic nerves in reflex facilitation and inhibition of gastric motility when mechanical nociceptive stimulation was delivered to either hind paw or abdominal skin, respectively. 2. After bilaterally sectioning the splanchnic nerves in vagal intact animals, the reflex facilitation of gastric motility produced by hind paw stimulation persisted, but the reflex inhibition previously produced by abdominal skin stimulation disappeared. 3. Hind paw stimulation increased efferent activity of the gastric branch of the vagus nerve, but stimulation of abdominal skin had little influence. 4. Bilateral vagotomy in splanchnic nerve intact animals did not influence the gastric reflex inhibition by abdominal skin stimulation, but either abolished gastric reflex facilitation produced by hind paw stimulation or reversed the reflex facilitation response to slight reflex inhibition. 5. Efferent activity of the gastric sympathetic nerve was greatly increased by abdominal skin stimulation, and was either slightly increased or not influenced by hind paw stimulation. 6. It was concluded that reflex increase of efferent activity of the gastric vagi was responsible for the gastric motility facilitation produced by hind paw stimulation, and also that reflexly increased efferent activity of the gastric sympathetic nerves resulted in gastric motility inhibition produced by abdominal skin stimulation. It is suggested efferents are inhibitory. 7. After spinal transection at the cervical level, the reflex facilitation of gastric motility previously produced by stimulation of a hind paw was completely abolished, or reversed to slight reflex inhibition, while reflex inhibition of gastric motility produced by stimulation of abdominal skin remained. It was concluded that the gastric reflex inhibition was a spinal reflex. 8. Interaction between reflex facilitation and inhibition of gastric motility during simultaneous stimulation of both hind paws and abdominal skin was observed as partial cancellation of each effect by the other. However, sympathetic reflex inhibition of gastric motility seemed to be much stronger than the vagal reflex facilitatory effect.

Kametani, H; Sato, A; Sato, Y; Simpson, A

1979-01-01

331

Gastrin Levels and Gastric Emptying Times in Rhesus Monkeys with a History of Acute Gastric Dilatation.  

National Technical Information Service (NTIS)

Abnormal gastric motility has been suggested as a possible causative factor for acute gastric dilatation observed in nonhuman primates. To evaluate gastric motility in a colony, fasting serum gastrin immunoreactivity and gastric emptying times were assess...

J. W. Fanton D. J. Cosgrove J. G. Golden

1995-01-01

332

Amygdalofugal modulation of the vago-vagal gastric motor reflex in rat.  

PubMed

In experiments on urethane anaesthetized rats the influence of electrical stimulation of the central nucleus of the amygdala (CNA) on gastric motility and activity of gastric-related neurons of the dorsal vagal complex was studied. Stimulation of the CNA effected spontaneous gastric motility and caused both excitatory and inhibitory changes of vagal-induced gastric relaxation. The most significant effects, mainly inhibitory, were observed under stimulation of the medial CNA. This amygdaloid area was found to influence activity of gastric-related neurons of the dorsal vagal complex. Excitatory and inhibitory changes of their vagal-induced responses under the amygdala stimulation manifested as general modulation of all phases of the reaction or selective modulation of some of them. These mechanisms may lie at the base of amygdalofugal modulation of gastric reflex activity. PMID:12044651

Liubashina, O; Bagaev, V; Khotiantsev, S

2002-06-14

333

Gastric stem cells and gastric cancer stem cells  

PubMed Central

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.

Han, Myoung-Eun

2013-01-01

334

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

335

siRNA targeting midkine inhibits gastric cancer cells growth and induces apoptosis involved caspase-3,8,9 activation and mitochondrial depolarization  

Microsoft Academic Search

Midkine (MK), a heparin-binding growth factor, is expressed highly in various malignant tumors, so it acts as attractive therapeutic\\u000a target. In the present study, we used siRNA targeting MK to downregulate human MK expression in human gastric cancer cell\\u000a line BGC823 and SGC7901 so as to determine the advantages of this anticancer therapeutic. The cell proliferation was evaluated\\u000a by a

Qingling Wang; Yahong Huang; Yanhong Ni; Hui Wang; Yayi Hou

2007-01-01

336

CD40 signaling activated by agonistic anti-CD40 monoclonal antibody 5C11 has different effects on biological behavior of gastric carcinoma cells  

Microsoft Academic Search

A gastric cancer cell line, AGS has high-level expression of CD40. CD40 is present on the surfaces of a large variety of cells, including B cells, endothelial cells, dendritic cells and some carcinoma cells, and delivers signals regulating diverse cellular responses, such as proliferation, differentiation, growth suppression, cell death. In this research, the expression of CD40 and CD40 transcription in

Rui Li; Wei-chang Chen; Wei-peng Wang; Wen-yan Tian; Xue-guang Zhang

2010-01-01

337

Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action  

Microsoft Academic Search

In previous studies [Gut 35 (1994) 896–904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and\\/or OME affect expression

Andrzej S Tarnawski; Morimasa Tomikawa; Masayuki Ohta; I. James Sarfeh

2000-01-01

338

Effect of type and level of fibre on gastric microbial activity and short-chain fatty acid concentrations in gestating sows  

Microsoft Academic Search

The present study was undertaken to study the effect of dietary fibre on gastric microflora, and short-chain fatty acids (SCFA) concentrations at different time after feeding in gestating sows. Three experimental diets consisting of two dietary fibre-rich diets and one concentrated, low dietary fibre diet (C) were used. One fibre-rich diet contained soluble dietary fibre from sugar beet pulp (S)

J. F Wang; D. F Li; B. B Jensen; K Jakobsen; J. J Xing; L. M Gong; Y. H Zhu

2003-01-01

339

Disordered gastric motor function in diabetes mellitus  

Microsoft Academic Search

Summary  The application of novel investigative techniques has demonstrated that disordered gastric motility occurs frequently in diabetes mellitus. Gastric emptying is abnormal in about 50% of diabetic patients and delay in gastric emptying of nutrient-containing meals is more common than rapid emptying. The blood glucose concentration influences gastric motility in diabetes. In IDDM patients, gastric emptying is retarded during hyperglycaemia and

M. Horowitz; R. Fraser

1994-01-01

340

NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36.  

PubMed

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynaptic ?-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36. PMID:23118791

Gao, Xinyan; Qiao, Yongfa; Jia, Baohui; Jing, Xianghong; Cheng, Bin; Wen, Lei; Tan, Qiwen; Zhou, Yi; Zhu, Bing; Qiao, Haifa

2012-10-15

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

[Immunological indices in gastric cancer].  

PubMed

Immunological indices were assayed in 167 patients with gastric cancer. Tumor growth involved reduction in levels of neutrophil peroxide (p<0.05), CD3+ and CD19+-cells (p<0.05) as well as intensification of apoptosis of lymphocytes (p<0.05). As monocytic and granulocytic phagocytosis (p<0.001) and HLA-DR-expression in monocytes (p<0.001) diminished, and mitogen-induced proliferative activity of mononuclear cells suppressed (p<0.05), total and relative levels of CD8+-cells (p<0.05) and spontaneous proliferative activity of mononuclear cells (p<0.05) in peripheral blood increased. Such changes should not be reganded as expression of immunosuppression alone. Mechanisms of immunological failure inherent in tumor growth need to be investigated further. PMID:17191703

Solov'eva, I G; Egorov, D N; Bardosanidze, K V; Chernykh, E R; Leplina, O Iu; Kozhevnikov, V S; Abramov, V V; Kozlov, V A

2006-01-01

343

Selective expression of vasoactive intestinal peptide (VIP)2/pituitary adenylate cyclase-activating polypeptide (PACAP)3 receptors in rabbit and guinea pig gastric and tenia coli smooth muscle cells.  

PubMed

In both functional and radioligand binding studies of gastric smooth muscle from rabbit and guinea pig, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) show equal potency indicating that the receptor type is either a VIP1/PACAP2 or a VIP2/PACAP3 receptor. We have characterized the VIP/PACAP receptor expressed in freshly dispersed and cultured gastric and tenia coli smooth muscle cells of rabbit and guinea pig by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern analysis, and cloning of the first extracellular domain. Specific primers based on cDNA sequences for rat VIP1/PACAP2, VIP2/PACAP3 and PACAP1 receptors were designed spanning the first extracellular domain. A 275 base pair product corresponding to VIP2/PACAP3 receptor was amplified by RT-PCR in muscle cells from both species. No RT-PCR product was obtained with primers for VIP1/PACAP2 and PACAP1 receptors. The deduced amino acid sequences showed 90% similarity in rabbit and 77% in guinea pig to the sequence in rat. The location of the aspartate, tryptophan and glycine residues and all six N-terminal cysteines required for VIP binding were conserved. The sequence in guinea pig tenia coli differed from that in guinea pig stomach by two amino acid residues, Phe40 and Phe41. Northern analysis revealed a single 3.9 kilobase (kb) mRNA corresponding to VIP2/PACAP3 receptors in rabbit and a 2.1 kb mRNA in guinea pig gastric and tenia coli muscle cells. We conclude that only VIP2/PACAP3 receptors are expressed in smooth muscle cells of rabbit and guinea pig. The two amino acid difference in the sequence obtained from guinea pig tenia coli may reflect the distinct binding and functional properties of this tissue. PMID:9809806

Teng, B; Murthy, K S; Kuemmerle, J F; Grider, J R; Makhlouf, G M

1998-10-16

344

The effectiveness of gastric bypass over gastric partition in morbid obesity: consequence of distal gastric and duodenal exclusion.  

PubMed Central

Eighty-seven morbidly obese patients were prospectively randomized to two operations: gastric bypass was performed on 42 and gastric partition on 45. Gastric bypass proved to be more effective; gastric bypass patients lost 15% more of their original weight at 12 months and 21% more at 18 months. There were no failures in the gastric bypass group; 28 of the 45 operations failed in the gastric partition group. An additional 60 patients underwent gastric bypass since the completion of the study. In the total series of 147 patients who underwent gastric bypass or gastric partition, there was no mortality, and the surgical complication rate was 12%. Because the gastric pouches and the anastomoses were similar in the two operations, the superiority of the gastric bypass may well be due to a heretofore unexplained effect of distal gastric and duodenal exclusion.

Pories, W J; Flickinger, E G; Meelheim, D; Van Rij, A M; Thomas, F T

1982-01-01

345

Effects of Diacerein on Indomethacin-Induced Gastric Ulceration  

Microsoft Academic Search

We investigated the effect of diacerein, an antiosteoarthritic agent, and its metabolite, rhein, on the production of reactive oxygen species (ROS) from neutrophils as well as the protective effect of diacerein on indomethacin-induced gastric ulceration and its protection mechanism. Rhein inhibited the ROS production from N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate-activated human peripheral neutrophils. Indomethacin-induced gastric ulceration was significantly inhibited by oxygen radical

Tadafumi Tamura; Toshihide Yokoyama; Kenji Ohmori

2001-01-01

346

Abnormal Growth Factor\\/Cytokine Network in Gastric Cancer  

Microsoft Academic Search

Gastric cancer cells express a broad spectrum of the growth factor\\/cytokine receptor systems that organize the complex interaction\\u000a between cancer cells and stromal cells in tumor microenvironment, which confers cell growth, apoptosis, morphogenesis, angiogenesis,\\u000a progression and metastasis. However, these abnormal growth factor\\/cytokine networks differ in the two histological types of\\u000a gastric cancer. Importantly, activation of nuclear factor-kB pathway by Helicobacter

Eiichi Tahara

2008-01-01

347

Gastric Dysrhythmias and Delayed Gastric Emptying in Patients with Functional Dyspepsia  

Microsoft Academic Search

An association between dyspepsia, gastricmotility disorders, and myoelectrical abnormalities hasbeen noted. The objective of the present study was toinvestigate both antral myoelectrical activity and gastric emptying in patients with functionaldyspepsia (FD). Electrogastrography (EGG) was performedin 25 adult patients with FD, which had been evaluatedby score. After an overnight fast, for 1 hr in the pre- and postprandial state (370 kcalliquid-solid

Boris Pfaffenbach; Romuald J. Adamek; Christian Bartholomaus; Martin Wegener

1997-01-01

348

Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.  

PubMed

The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations. PMID:23283817

Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

2013-01-03

349

Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation.  

PubMed

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains. PMID:15456896

Chang, Ya Jen; Wu, Ming Shiang; Lin, Jaw Town; Sheu, Bor Shyang; Muta, Tatsushi; Inoue, Hiroyasu; Chen, Ching-Chow

2004-09-29

350

Absence of NF-?B subunit p50 ameliorates cold immobilization stress-induced gastric ulcers.  

PubMed

Stress ulcers are a common complication in critically ill patients, but the underlying mechanism is little known. This study characterized the function of the p50 subunit of NF-?B in an experimental model of cold immobilization stress-induced gastric ulcers. Stress-induced gastric mucosal inflammation and gastric injury were examined in wild-type and NF-?B p50-deficient mice. When subjected to cold immobilization stress, NF-?B was rapidly activated in the gastric mucosa in WT mice whereas the majority of ?B DNA-binding activity was abrogated from p50(-/-) mice. Deficiency of p50 ameliorated stress-induced expression of TNF-?, MIP-2, and ICAM-1, resulting in reduced mucosal accumulation of neutrophils and gastric injury. These data indicated a critical role for the p50 in the gastric mucosal inflammatory response to cold restraint stress. PMID:23583384

Ye, Bin; Zhou, Pan-Yu; Jia, Meng; Cheng, Xiao-Song; Jia, Yi-Tao; Xu, Shuo-Gui

2013-04-10

351

Extraction of gastric parietal cell autoantigen  

PubMed Central

The distribution of gastric parietal cell autoantigen in subcellular fractions of bovine abomasum mucosa has been assessed by the capacity to neutralize antigastric parietal cell activity of pernicious anaemia serum. By far the greater proportion of the antigenic activity was in the microsomal fraction. Active material was soluble in 6 M-urea, pH 7·3. Removal of urea by dialysis produced an active suspension which on centrifuging gave an active sediment and an inactive supernatant. Electronmicroscopic and ultraviolet absorption evidence suggests that the antigenic component(s) of the microsomal fraction is associated with the smooth membranes and not with the ribosomes. ImagesFig. 1

Ward, H. A.; Nairn, R. C.

1967-01-01

352

Nitric oxide and gastric relaxation.  

PubMed

Pentagastrin enhanced the volume increase caused by isobaric gastric distension in conscious dogs. This effect could be abolished by inhibitors of acid secretion and mimicked by histamine. The increased compliance after pentagastrin was not affected by L-nitroarginine (L-NNA), a blocker of nitric oxide (NO) synthase. L-NNA itself reduced the volume increases caused by isobaric gastric distension. Intralipid administration into the duodenum led to a gastric relaxation sensitive to inhibition by L-NNA. The inhibitory effect of L-NNA was partially reversed by L-arginine. Pentagastrin induces a gastric relaxation via a mechanism that involves gastric secretion but not nitric oxide, whereas intraduodenal intralipid induces a gastric relaxation via a NO-dependent mechanism. PMID:7995223

Schuurkes, J A; Meulemans, A L

1994-12-01

353

Annexin A6 is down-regulated through promoter methylation in gastric cancer  

PubMed Central

Background: The aberrant activation of oncogenic signaling such as Ras/MAPK signaling is a frequent event in human cancers. In addition to genetic changes, epigenetic silencing of inhibitors in Ras/MAPK signaling contributes to the activation of Ras/MAPK signaling. Recently, ANXA6 has been shown to interact with Ras-GAP1 and inhibit Ras activation in human breast cancer. However, whether and how it is involved in human cancers remain unknown. Methods: Real-time PCR was used to determine ANXA6 expression in gastric cancer cells and primary gastric carcinomas. Next, we explored the methylation of ANXA6 promoter in cell lines and tumor tissues with methylation-specific PCR and bisulfite genomic sequencing. We also investigated the function of ANXA6 in gastric cancer cells with colony formation assay and western blotting analysis. Results: ANXA6 was down-regulated in gastric cancer cells and primary gastric carcinomas. Ectopic ANXA6 expression inhibited the growth of gastric cancer cells and the activity of Ras/MAPK signaling. Its expression was restored after pharmaceutical demethylation. ANXA6 promoter was methylated in gastric cancer cell lines (6/6) and primary gastric carcinoma tissues (29/156). Interestingly, the knockdown of oncoprotein Yin Yang 1 (YY1) also restored ANXA6 expression and promoted the demethylation of ANXA6 promoter. However, ANXA6 methylation was not associated with clinical parameters such as differentiation, and TNM staging. Neither Kaplan-Meier Curve nor Cox regression analysis revealed a significant role of ANXA methylation to predict the survival of gastric cancer patients. Conclusions: We firstly reported that ANXA6 is epigenetically silenced through promoter methylation in human cancers and YY1 is important to initiate or maintain ANXA6 promoter methylation in gastric cancer cells. ANXA6 functions as a tumor suppressor in gastric cancer cells through the inhibition of Ras/MAPK signaling. ANXA6 methylation is not a prognostic factor for gastric cancer patients.

Wang, Xian; Zhang, Shengjie; Zhang, Jianbin; Lam, Emily; Liu, Xin; Sun, Jie; Feng, Lifeng; Lu, Haiqi; Yu, Jun; Jin, Hongchuan

2013-01-01

354

Human primary gastric dendritic cells induce a Th1 response to H. pylori  

Microsoft Academic Search

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 and are more prevalent and more activated in the gastric mucosa of H. pylori-infected subjects. H.

D Bimczok; R H Clements; K B Waites; L Novak; D E Eckhoff; P J Mannon; P D Smith; L E Smythies

2010-01-01

355

Helicobacter pylori and gastric carcinogenesis  

Microsoft Academic Search

Gastric carcinoma is the second leading cause of cancer-related deaths in the world, accounting for more than 700,000 deaths\\u000a each year. Recent studies have revealed that infection with cagA-positive Helicobacter pylori plays an essential role in the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system, where it

Masanori Hatakeyama

2009-01-01

356

Epidemiology of gastric cancer.  

PubMed

The most recent estimates of global cancer incidence indicate that in 1990 stomach cancer was the second most frequent cancer in the world (after lung cancer), with about 800,000 new cases diagnosed every year (Parkin et al., 1999). Steady declines in incidence rates of gastric cancer have been observed worldwide in the last few decades. The exact causes of the decline are not well understood, but may include improvements in diet and food storage and a decline in the prevalence of Helicobacter pylori infection. Dietary modifications remain potentially one of the most important tools for the prevention of gastric cancer. Control of H. pylori infection, by indirect means such as improving the general sanitary conditions or by direct intervention such as eradication or immunization, is also likely to offer great potential for prevention. PMID:15055304

Plummer, Martyn; Franceschi, Silvia; Muńoz, Nubia

2004-01-01

357

Rett syndrome and gastric perforation.  

PubMed

Rett Syndrome is associated with decreased peristaltic esophageal waves and gastric dysmotility, resulting in swallowing difficulties and gastric dilation. Rarely, gastric necrosis and perforation occur. Our case represents the third reported case of gastric necrosis and perforation associated with Rett Syndrome. A 31-year-old female after 11 hours of intermittent emesis and constant, sharp abdominal pain presented with evidence of multiorgan system failure including hypovolemic shock, metabolic acidosis, coagulopathy, and hepatorenal failure. A chest radiograph revealed intra-abdominal free air necessitating emergent laparotomy. During exploration, a severely dilated, thin-walled stomach with an area of necrosis and gross perforation was noted. Wedge resection of the necrotic tissue and primary closure were performed. Despite aggressive perioperative resuscitation and ventilation support, the patient died 3 hours postoperatively secondary to refractory shock and hypoxemia. Severe gastric dilation can occur with Rett Syndrome and may cause gastric necrosis and perforation. Prolonged elevated gastric pressures can decrease perfusion and may contribute to perforation. Timely decompression via percutaneous endoscopic or surgical gastrostomy could decrease the risk of perforation particularly when significant gastric distention is present. Consideration of gastric necrosis and perforation in patients with Rett Syndrome may lead to earlier intervention and decreased mortality. PMID:18453295

Shah, Malay B; Bittner, James G; Edwards, Michael A

2008-04-01

358

Serum biomarker panels for the diagnosis of gastric adenocarcinoma  

PubMed Central

Background: Currently, serum biomarkers, which are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinoma do not exist. Therefore, this study identified a panel of serum biomarkers for the diagnosis of gastric adenocarcinoma. Methods: A 29-plex array platform with 29 biomarkers, consisting of 11 proteins discovered through proteomics and 18 previously known to be cancer-associated, was constructed. A test/training set consisting of 120 gastric adenocarcinoma and 120 control samples were examined. After 13 proteins were selected as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 95 gastric adenocarcinoma and 51 control samples. Results: Epidermal growth factor receptor (EGFR), pro-apolipoprotein A1 (proApoA1), apolipoprotein A1, transthyretin (TTR), regulated upon activation, normally T-expressed and presumably secreted (RANTES), D-dimer, vitronectin (VN), interleukin-6, ?-2 macroglobulin, C-reactive protein and plasminogen activator inhibitor-1 were selected as classifiers in the two algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (>88%). These algorithms also accurately classified in the validation set (>85%). Conclusion: Two panels of combinatorial biomarkers, including EGFR, TTR, RANTES, and VN, are developed, which are less invasive method for the diagnosis of gastric adenocarcinoma. They could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy.

Ahn, H S; Shin, Y S; Park, P J; Kang, K N; Kim, Y; Lee, H-J; Yang, H-K; Kim, C W

2012-01-01

359

Tricholithobezoar causing gastric perforation.  

PubMed

A bezoar is an intraluminal mass formed by the accumulation of undigested material in the gastrointestinal tract. Trichobezoar is a rare condition seen almost exclusively in young women with trichotillomania and trichotillophagia. When not recognized, the trichobezoar continues to grow, which increases the risk of severe complications such as gastric ulceration and even perforation. Formation of a gallstone within the trichobezoar (tricholithobezoar) is an event that has not yet been described. We report the case of a 22-year-old woman admitted to the emergency room with signals and symptoms of an epigastric mass and perforative acute abdomen. Radiological study revealed bilateral pneumoperitoneum. Personal history revealed depressive syndrome, trichotillomania and trichophagia. With a diagnosis of visceral perforation, an urgent exploratory laparotomy was performed. This confirmed the diagnosis of gastric perforation due to a large trichobezoar with the formation of a gastrolith that was removed by anterior gastrotomy. Biochemical study of the gastric stone revealed that it was composed of bile salts. There were no complications. The patient was discharged on the 5th postoperative day and was referred for psychiatric treatment. PMID:22379468

Santos Valenciano, Juliana; Nonose, Ronaldo; Bragattini Cruz, Rodrigo; Tiemi Sato, Daniela; Monteiro Fernandes, Felipecappellette; Fabrício Nascimento, Enzo; Real Martinez, Carlos Augusto

2012-01-13

360

Tricholithobezoar Causing Gastric Perforation  

PubMed Central

A bezoar is an intraluminal mass formed by the accumulation of undigested material in the gastrointestinal tract. Trichobezoar is a rare condition seen almost exclusively in young women with trichotillomania and trichotillophagia. When not recognized, the trichobezoar continues to grow, which increases the risk of severe complications such as gastric ulceration and even perforation. Formation of a gallstone within the trichobezoar (tricholithobezoar) is an event that has not yet been described. We report the case of a 22-year-old woman admitted to the emergency room with signals and symptoms of an epigastric mass and perforative acute abdomen. Radiological study revealed bilateral pneumoperitoneum. Personal history revealed depressive syndrome, trichotillomania and trichophagia. With a diagnosis of visceral perforation, an urgent exploratory laparotomy was performed. This confirmed the diagnosis of gastric perforation due to a large trichobezoar with the formation of a gastrolith that was removed by anterior gastrotomy. Biochemical study of the gastric stone revealed that it was composed of bile salts. There were no complications. The patient was discharged on the 5th postoperative day and was referred for psychiatric treatment.

Santos Valenciano, Juliana; Nonose, Ronaldo; Bragattini Cruz, Rodrigo; Tiemi Sato, Daniela; Monteiro Fernandes, FelipeCappellette; Fabricio Nascimento, Enzo; Real Martinez, Carlos Augusto

2012-01-01

361

Nitrate and Nitrite in Normal Gastric Juice  

Microsoft Academic Search

The nitrate and nitrite levels of 75 gastric juice samples from young and healthy fasting volunteers were examined. For both parameters a dependence on the specific pH value of the secretion was detected. The rise of the nitrite level from normal 0.1 ppm in the acid to 1.4 ppm in the neutral range can be explained by the activity of

R. L. Mueller; H.-J. Hagel; H. Wild; H. Ruppin; W. Domschke

1986-01-01

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

2013-08-18

363

Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric mucosa against stress.  

PubMed

Acute gastric mucosal lesions represent an important clinical problem. The experimental model of acute gastritis such as water immersion restraint (WRS) stress is useful tool in examination of pathomechanism of acute gastric damage. Nitric oxide (NO) plays an important role in the maintenance of gastric barrier, however the role of reactive oxygen species (ROS) in the interaction between NO and gastric mucosa integrity has been little studied. The purpose of our present study was to explain the participation of ROS in healing of WRS-induced gastric lesions accelerated by NO. Experiments were carrying out on 120 male Wistar rats. To assess gastric blood flow (GBF) laser Doppler flowmeter was used. The number of gastric lesions was established by planimetry. The colorimetric assays were used to determine gastric tissue level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the products of lipid peroxidation by ROS, as well as superoxide dismutase (SOD) activity, the enzyme scavanger of ROS. We demonstrated that 3.5 h of WRS resulted in appearance of acute gastric mucosal lesions accompanied by a significant decrease of GBF. Biological effects of ROS were estimated by measuring tissue level of MDA and 4-HNE, as well as the SOD activity. It was demonstrated that 3.5 h of WRS led to significant increase of MDA and 4-HNE mucosal level, that was accompanied by a decrease of SOD activity. Pretreatment with NO-donors (SIN-1, SNAP, nitroglycerin, NO-ASA) resulted in reduction of gastric lesions number, increment of GBF, decrease of MDA and 4-HNE tissue level and increase of SOD activity. Suppression of ROS play an important role in NO-donors action in gastroprotection against gastric acute lesions induced by 3.5 h of WRS. NO-donors cause an attenuation of lipid peroxidation as documented by a decrease of MDA and 4-HNE levels and enhancement of antioxidative properties as evidenced by increase of SOD activity. PMID:18812632

S Kwiecien, S; Pawlik, M W; Brzozowski, T; Konturek, P C; Sliwowski, Z; Pawlik, W W; Konturek, S J

2008-08-01

364

Gastroprotective Effect of Selenium on Ethanol-Induced Gastric Damage in Rats  

PubMed Central

In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 ?g/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 ?g/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging.

Kim, Jeong-Hwan; Park, Shin-Hyung; Nam, Soo-Wan; Choi, Yung-Hyun

2012-01-01

365

Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats.  

PubMed

Indomethacin (IND) is a non-steroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the protective effect of selenium (SEL), grape seed extract (GSE), and both on IND-induced gastric mucosal ulcers in rats. Sprague-Dawley rats (200-250 g) were given SEL, GSE, and both by oral gavage for 28 days, and then gastric ulcers were induced by oral administration of 25 mg/kg IND. Malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants, prostaglandin E2 (PGE2) in gastric mucosa, and serum tumor necrosis factor alpha (TNF-?) were measured. Moreover, gastric ulcer index and preventive index were determined. Indomethacin increased the gastric ulcer index, MDA, TNF-?, and decreased PGE2 and non-enzymatic (GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants. Pretreatment with SEL, GSE, and both significantly decreased the gastric ulcer index, MDA, and TNF and increased antioxidants and PGE2. Histopathological observations confirm the gastric ulcer index and biochemical parameters. Selenium and GSE have a protective effect against IND-induced gastric ulcers through prevention of lipid peroxidation, increase of GSH, activation of radical scavenging enzymes, PGE2 generation, and anti-inflammatory activity. Co-administration of GSE and SEL is more effective than GSE or SEL alone. PMID:23456451

Abbas, Amr M; Sakr, Hussein F

2013-03-01

366

Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats.  

PubMed

Anti-tumor necrosis factor alpha (TNF-alpha) treatment decreases nitric oxide (NO) synthesis and ameliorates the hyperdynamic circulation in portal hypertensive rats. We have recently demonstrated that nitric oxide synthase isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that resultant NO overproduction probably is responsible for the increased susceptibility of the mucosa to damage. In the present study, we examined whether TNF-alpha is overexpressed in portal hypertensive gastric mucosa and whether anti-TNF-alpha treatment affects gastric NOS3 messenger RNA (mRNA) and protein expression. We examined plasma concentrations of TNF-alpha and its protein expression in gastric specimens from portal hypertensive and sham-operated rats using Western blotting and immunohistochemistry. We also measured gastric mucosal blood flow, gastric expression of NOS3 mRNA and protein, and NOS3 enzyme activity in rats with and without TNF-alpha-neutralizing antibody treatment. The TNF-alpha protein levels in portal hypertensive stomachs were significantly increased by 57% compared with levels in sham-operated controls. TNF-alpha antibody treatment normalized gastric mucosal blood flow in portal hypertensive stomachs and significantly reversed overexpression of gastric NOS3 mRNA, protein, and its enzyme activity in portal hypertensive rats by 48%, 45%, and 33%, respectively. These results suggest that TNF-alpha may regulate NOS3 expression in the portal hypertensive stomach and that anti-TNF-alpha treatment may ameliorate the pathophysiological abnormalities of portal hypertensive gastric mucosa. PMID:9537427

Ohta, M; Tarnawski, A S; Itani, R; Pai, R; Tomikawa, M; Sugimachi, K; Sarfeh, I J

1998-04-01

367

Gastric strongyloidiasis as multiple small gastric nodules  

PubMed Central

Summary Background: Strongyloidiasis, a common intestinal parasitic infection, is endemic in tropical and subtropical regions and occurs sporadically in temperate areas. It is endemic in Guilan province, Iran, and especially affects the rural population. Case Report: We report the case of a 43-year-old woman living in Anzali (in the north of Iran), with dyspepsia and epigastric pain for 2 years, unresponsive to H2 receptor antagonists and proton pump inhibitors. Upper gastrointestinal endoscopy was done and showed multiple small nodules at the stomach. The pathologist reported Strongyloides. Treatment with Ivermectin and antibiotic triple therapy was done. She responded well to treatment and 6 months later an upper gastrointestinal endoscopy revealed no significant lesions and all nodules had disappeared. Strongyloidiasis is usually not severe and frequently is nonspecific. For this reason, the infection is easily ignored by both the patients and physicians. Conclusions: Although gastric involvement shows nonspecific symptoms, the possibility should be carefully considered by clinicians who practice in endemic areas.

Shafaghi, Afshin; Askari, Kurosh; Hajizadeh, Hadi; Mansour-Ghanaei, Fariborz

2012-01-01

368

[Early gastric cancer. Clinical contribution].  

PubMed

The authors report their experience on 37 cases of Early Gastric Cancer on 1978-1990 period. They underline the excellent results obtained with subtotal gastrectomy and lynphectomy without deaths neither returns. They stress the diagnostic precision of endoscopic exam now of first choice in the early diagnosis of Early Gastric Cancer. PMID:1298974

Pillitu, A; Carletti, N; Durzi, S; Terzi, G; Menghini, L; Degli Albizi, S

369

Helicobacter pylori and Gastric Erosions  

Microsoft Academic Search

Background\\/Aims:Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers. Methods: 175 asymptomatic subjects underwent upper gastrointestinal endoscopy. Antral biopsies were taken for bacterial

Frank S. Lehmann; Eberhard L Renner; Beat Meyer-Wyss; Clive H. Wilder-Smith; Luca Mazzucchelli; Charles Ruchti; Jürgen Drewe; Christoph Beglinger; Hans S. Merk

2000-01-01

370

Expression and prognostic significance of Livin in gastric cancer.  

PubMed

Livin is one of the most important members of the inhibitor of apoptosis protein family. It is overexpressed in several types of tumors and may have prognostic significance. The present study investigated the biological role of Livin in the oncogenic behavior of gastric cancer cells, the expression of Livin in gastric cancer tissue and the relationship of its expression with various clinicopathological parameters and patient survival. Small interfering RNA blocked Livin gene expression in AGS and SNU638 human gastric cancer cell lines. The expression of Livin was investigated in gastric cancer tissues by RT-PCR, western blotting and immunohistochemistry. The associations with various clinicopathological parameters and survival were analyzed. Livin knockdown inhibited tumor cell migration, invasion and proliferation in AGS and SNU638 cells. Livin knockdown induced apoptosis by activating caspase-3, caspase-7 and PARP. Livin knockdown induced cell cycle arrest by a decrease in cyclin D1, cyclin-dependent kinase 4 and 6 and an increase in expression of p21 and p27. The ERK1/2 and JNK signaling pathways were inhibited by Livin knockdown. Livin expression was upregulated in gastric cancer tissues at the mRNA and protein levels. However, no significant correlation was found between Livin expression and various clinicopathological parameters including survival. In conclusion, Livin expression may be important in the alteration of invasive and oncogenic phenotypes of gastric cancer cells. The prognostic relevance of Livin remains unclear. PMID:24008725

Chung, Cho-Yun; Park, Young-Lan; Kim, Nuri; Park, Hyung-Chul; Park, Hyun-Bum; Myung, Dae-Seong; Kim, Jong-Sun; Cho, Sung-Bum; Lee, Wan-Sik; Joo, Young-Eun

2013-09-06

371

Helicobacter Pylori CagA and Gastric Carcinogenesis.  

PubMed

Objectives: This study aimed to demonstrate the tyrosine phosphorylation motif (TPM) and 3' region structure of the Helicobacter pylori CagA gene as well as its SHP-2 binding activity in AGS cells and relation to gastric carcinogenesis. Methods: Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells. Results: Except for strain 547, all strains from the gastric adenocarcinoma patients were positive for CagA by PCR and had three EPIYA copy motifs. Western blotting showed that all strains were positive for CagA protein expression (100%), CagA protein translocation (100%), and SHP-2 binding (100%). CagA protein expression was significantly higher in the gastric adenocarcinoma patients than in the duodenal ulcer patients (P=0.0023). CagA protein translocation and SHP-2 binding in the gastric adenocarcinoma patients were higher than those in the duodenal ulcer patients, but no significant differences were found between the two groups (P=0.59, P=0.21, respectively). Conclusions: The TPMs and 3' region structures of the H. pylori CagA gene in the duodenal ulcer and gastric adenocarcinoma patients have no significant differences. PMID:23464450

Zheng, Ri-Nan; Li, Shu-Rong; Masahiro, Asaka

2012-01-01

372

Do we need gastric acid?  

PubMed

Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression. PMID:18594142

Pohl, D; Fox, M; Fried, M; Göke, B; Prinz, C; Mönnikes, H; Rogler, G; Dauer, M; Keller, J; Lippl, F; Schiefke, I; Seidler, U; Allescher, H D

2008-07-02

373

Monosodium L-glutamate added to a high-energy, high-protein liquid diet promotes gastric emptying1-3  

Microsoft Academic Search

Background: Free glutamate activates taste receptors on nerves in the oral cavity to elicit a unique taste known as umami .R ecently, umami taste receptors were also found in the gastric mucosa. Although reports suggest that mucosal receptors may respond to free gluta- mate to modulate gastric function, no evidence of any effect on gastric emptying has been documented. Objective:

Hiroaki Zai; Motoyasu Kusano; Hiroko Hosaka; Yasuyuki Shimoyama; Atsuto Nagoshi; Masaki Maeda; Osamu Kawamura; Masatomo Mori

374

Helicobacter pylori in promotion of gastric carcinogenesis  

Microsoft Academic Search

Gastric atrophy and intestinal metaplasia are considered the earliest phenotypic changes in the cascade of events leading from normal mucosa to intestinal-type gastric cancer, and epidemiological evidence linksHelicobacter pylori to gastric epithelial malignancies. To evaluate any causal relationship between bacterial infection and atrophic metaplastic lesions, gastric pathology was histologically and histochemically evaluated in 267 consecutive, nonulcerous, untreated subjects, with attention

Massimo Rugge; Mauro Cassaro; Gioacchino Leandro; Raffaele Baffa; Claudio Avellini; Pantaleone Bufo; Vincenzo Stracca; Giuseppe Battaglia; Alfredo Fabiano; Antonio Guerini; Francesco di Mario

1996-01-01

375

Helicobacter pylori infection and gastric MALT lymphoma  

Microsoft Academic Search

Helicobacter pylori infection is implicated in the devel- opment of two different gastric cancers: gastric adeno- carcinoma and gastric MALT lymphoma. The association with the gastric MALT lymphoma is strong and causal. It is currently the only cancer which can be treated by a simple antibiotic treatment. However, the evolution of an H. pylori infection towards lymphoma is exceptional. Host

Lehours P; Mégraud F

2005-01-01

376

Gastroprotective Agent Rebamipide Induces Cyclooxygenase2 (COX2) in Gastric Epithelial Cells  

Microsoft Academic Search

Cyclooxyngease-2 (COX-2) is a key enzyme in prostaglandin (PG) synthesis, and COX-2 induction plays an important role in the healing of gastric ulceration. Rebamipide is a gastroprotective agent and attenuates the activity of neutrophils. A number of reports have shown that rebamipide treatment increases PG production in the gastric mucosa {in vivo}. Although its clinical significance in ulcer healing has

Hiroaki Murata; Yuki Yabe; Shingo Tsuji; Masahiko Tsujii; Hai Ying Fu; Kayoko Asahi; Hiroshi Eguchi; Sunao Kawano; Norio Hayashi

2005-01-01

377

The protective effect and action mechanism of Vaccinium myrtillus L. on gastric ulcer in mice.  

PubMed

Vaccinium myrtillus L. anthocyanoside (VMA) is used as a folk medicine to treat diseases related to gastric ulcers in northern Europe. However, the effects of VMA and its detailed mechanism on gastric ulcer have not been investigated sufficiently. Therefore, the aim of the present study was to investigate the protective effects of VMA on gastric mucosal damage in a murine gastric ulcer model. First the effects of VMA on ethanol-induced gastric ulcers in mice were investigated. Then, the levels of lipid peroxide in murine stomach homogenates were measured to investigate the antioxidative effects of VMA. In addition, the free radical scavenging activity of VMA and its main anthocyanidins were evaluated by electron spin resonance measurement. Oral administration of VMA (10, 30 and 100?mg/kg) significantly protected gastric mucosa against HCl/ethanol-induced gastric ulcers. Furthermore, VMA inhibited lipid peroxide levels in a concentration-dependent manner and showed high scavenging activity against the superoxide anion radical (·O(2) (-) ) and the hydroxyl radical (·OH). Anthocyanidins also showed scavenging activity against the ·O(2) (-) , while only delphinidin showed high scavenging activity against the ·OH. These findings indicate that the protective effects of VMA on HCl/ethanol-induced gastric mucosal injury may be partially due to the antiperoxidative effects of anthocyanidins. PMID:21290441

Ogawa, Kenjirou; Oyagi, Atsushi; Tanaka, Junji; Kobayashi, Saori; Hara, Hideaki

2011-02-03

378

Phytohaemagglutinin inhibits gastric acid but not pepsin secretion in conscious rats  

Microsoft Academic Search

Phytohaemagglutinin (PHA), a kidney bean lectin, is known for its binding capability to the small intestinal surface. There has been no data available, however, on the biological activity of PHA in the stomach. Recent observations indicate that PHA is able to attach to gastric mucosal and parietal cells. Therefore, we examined whether PHA affects gastric acid and pepsin secretion in

Krisztina Kordás; Gábor Szalmay; Susan Bardocz; Árpád Pusztai; Gábor Varga

2001-01-01

379

Facilitation of gastric motility induced by portal infusion of hyper- and hypotonic solution in rats  

Microsoft Academic Search

The effects of the portal infusion of hyper- and hypotonic solution on gastric motility in rats were investigated. The infusion of hypertonic saline into the portal vein (portal infusion) elicited a significant enhancement of gastric contractile activity. The portal infusion of water also produced this enhancement. However, the portal infusion of isotonic saline showed no significant enhancement; nor did the

Motoi Kobashi; Masatoshi Mizutani; Akira Adachi

1998-01-01

380

Prevalence of gastric ulcers in endurance horses--a preliminary report.  

PubMed

Gastric endoscopy was performed at the end of a 50 or 80 km endurance ride. Gastric ulceration was evident in 67% of the horses with ulcers on the squamous region of the stomach found in 57% of the horses and active bleeding of the glandular mucosa in 27%. Three horses (10%) had lesions only on the glandular mucosa. Values of albumin, creatinine and glucose were higher in horses without gastric lesions. We conclude that horses from endurance competitions have a high prevalence of gastric ulceration that is similar to that observed in performance horses. However the severity of ulceration is less severe than has been reported in Thoroughbred race horses in active training. Owners should be aware of the high prevalence of gastric ulceration in horses that perform in endurance competitions. The high incidence of active bleeding from the glandular mucosa of the stomach in these horses requires further investigation. PMID:14623148

Nieto, Jorge E; Snyder, Jack R; Beldomenico, Pablo; Aleman, Monica; Kerr, James W; Spier, Sharon J

2004-01-01

381

Hereditary Diffuse Gastric Cancer  

Microsoft Academic Search

\\u000a Gastric cancer is one of the leading worldwide causes of cancer death with about 866,000 deaths each year. The incidence varies\\u000a tremendously throughout the world, with the highest incidence occurring in South Korea at 66.5–72.5 per 100,000 males and\\u000a 19.5–30.4 per 100,000 females [1]. In contrast, incidence in the United States is about one-tenth that of South Korea, and\\u000a the

Prakash K. Pandalai; Sam S. Yoon

382

Gastric carcinoids (neuroendocrine neoplasms).  

PubMed

Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Studying menin and its complex interrelationship with gastrin may provide insight into tumor biology at the clinical level and in terms of basic cell biology (eg, the role of the epigenome in neuroendocrine cell proliferation), and lead to potential consideration of other targets that are known candidates for molecular-based therapies in other adenocarcinomas. PMID:23639647

Kidd, Mark; Gustafsson, Bjorn; Modlin, Irvin M

2013-03-01

383

The guggulsterone derivative GG-52 inhibits NF-?B signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.  

PubMed

Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-?B (NF-?B) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-? in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-?-induced activation of I?B kinase (IKK) and NF-?B signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-?B activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-?B signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-?B activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent. PMID:23125156

Kim, Jung Mogg; Kim, Su Hyun; Ko, Su Hyuk; Jung, Jireh; Chun, Jaeyoung; Kim, Nayoung; Jung, Hyun Chae; Kim, Joo Sung

2012-11-01

384