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Sample records for secretin-induced gastric relaxation

  1. Retardation of gastric emptying of solid food by secretin

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    Kleibeuker, J.H.; Beekhuis, H.; Piers, D.A.; Schaffalitzky de Muckadell, O.B.

    1988-01-01

    The effect of secretin at nearly physiologic plasma concentrations on the gastric emptying rate of solid food was studied in 12 healthy men. A /sup 99m/Tc colloid-labeled pancake was used as the test meal. The gastric emptying rate was measured during 1 h using a dual-headed gamma-camera, and was expressed as the half-time of the emptying curve. To prevent endogenous secretin release, 400 mg of cimetidine was given before the meal. Subjects were studied under three conditions: (1) during infusion of saline; (2) during continuous infusion of secretin, 6.6 pmol/kg.h; and (3) during three intermittent 10-min periods of secretin infusion, 7.6 pmol/kg.h during each period. Both continuous and intermittent infusion of secretin increased half-emptying time, by 133% and 55%, respectively. The plasma secretin concentration in condition 1 was 0.8 pM; plateau concentration in condition 2 was 9.8 pM; and integrated mean concentration in condition 3 was 4.8 pM. It is concluded that secretin at approximately physiologic plasma concentrations retards gastric emptying of solid food in humans.

  2. Actions of vasoactive intestinal peptide and secretin on chief cells prepared from guinea pig stomach

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    Sutliff, V.E.; Raufman, J.P.; Jensen, R.T.; Gardner, J.D.

    1986-01-01

    Vasoactive intestinal peptide and secretin increased cellular cAMP and pepsinogen secretion in dispersed chief cells from guinea pig gastric mucosa. With each peptide there was a close correlation between the dose-response curve for changes in cellular cAMP and that for changes in pepsinogen secretion. Vasoactive intestinal peptide- (10-28) and secretin- (5-27) had no agonist activity and antagonized the actions of vasoactive intestinal peptide and secretin on cellular cAMP and pepsinogen secretion. Studies of binding of 125 I-vasoactive intestinal peptide and of 125 -secretin indicated that gastric chief cells possess four classes of binding sites for vasoactive intestinal peptide and secretin and that occupation of two of these classes of binding sites correlates with the abilities of vasoactive intestinal peptide and secretin to increase cellular cAMP and pepsinogen secretion. What function, in any, is mediated by occupation by the other two classes of binding sites remains to be determined

  3. Insulin release by glucagon and secretin

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    Kofod, Hans; Andreu, D; Thams, P

    1988-01-01

    Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated...... the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M...... potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different....

  4. Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study.

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    Yang Won Min

    Full Text Available Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles.Gastric fundus muscle strips (12 circular and 13 longitudinal were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM, MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM, and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement.In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle. Tetrodotoxin abolished any EFS-induced motor response.The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation.

  5. Secretin radioimmunoassay using 125I-6-tyrosyl-secretin (6TS)

    International Nuclear Information System (INIS)

    Raptis, S.; Leitze, M.; Schlegel, W.; Pfeiffer, E.F.

    1975-01-01

    In radioimmunological determination of secretin difficulties are caused by the following two problems: firstly, in raising potent antibodies, and secondly in satisfactory labeling. All secretin RIAs described in the literature were carried out with traditional synthetic secretin (Young, Lazarus, Chisholm and Atkinson 1968; Boden and Chey 1973; Holohan, Murphy, Buchanan and Elmore 1973; Boehm, Lee and Chey 1974). Our study describes the development of an assay with sufficient sensitivity to measure circulating immunoreactive secretin in human blood, by using 125 I-6-TS, which is a product of Schwarz and Mann/USA (SM). (orig.) [de

  6. Production of antibodies against secretin and their use for radioimmunoassay of secretin

    International Nuclear Information System (INIS)

    Groetzki, C.

    1980-01-01

    Synthetic thyroglobulin was bonded to bovine albunia and thyroglobulin according to the principle of the carbodiimide condensation reaction. 16 rabbits were immunized with these conjugates and with unconjugated secretin. Secretin labelling with 125 I was carried out by the chloramin-T method. The tracer has a specific activity of 15.45 mCi/mg. A secretin RIA was developed using the double antibody method. The sensitivity of the system could be raised by variation of the specific activity of the tracer and optimisation of the incubation parameters. Antisera were compared. The titers of secretin/bovine albumine conjugate antisera were similar to the antisera against secretin thyroglobulin conjugate. The sensitivity of the standard curves was higher for secretin/bovine albumin conjugate antisera than for thyroglobulin conjugate antisera. Two antisera were tested for specificity. The detection threshold of antiserum S 5 IX was 12,43 pmol/l while the 50% intercept was at 55.45 pmol/l. This antiserum is particularly suitable for a secretin RIA. (orig./MS)

  7. Does secretin add value in pediatric magnetic resonance cholangiopancreatography?

    International Nuclear Information System (INIS)

    Trout, Andrew T.; Podberesky, Daniel J.; Serai, Suraj D.; Towbin, Alexander J.; Ren, Yan; Altaye, Mekebib

    2013-01-01

    Secretin - a hormone that stimulates pancreatic exocrine secretion - is described to improve visualization of the pancreatic duct by magnetic resonance cholangiopancreatography (MRCP). In our pediatric practice, however, we have not observed substantial benefit with the use of secretin. To determine whether secretin dilates and improves visualization of the pancreatic duct in pediatric MRCP. Retrospective evaluation of secretin-enhanced MRCPs performed over a 15-month period. One reviewer measured the pancreatic duct pre- and post-secretin and two reviewers, blinded to the administration of secretin, assessed image quality and subjective duct visibility. Similar assessments of the biliary tree served as internal controls. We reviewed 20 MRCPs in 17 children. Following secretin administration, there was a small (0.3 mm) but statistically significant increase in pancreatic duct diameter (P = 0.002) and small (<0.2 mm) but significant increase in intrahepatic bile duct diameter (P = 0.0104). On subjective review, there was no significant difference in image quality or duct visibility based on the administration of secretin. Secretin induces dilatation of the pancreatic duct but the value of that effect in pediatric MRCP is suspect given the small change in duct diameter and the lack of improvement in image quality and duct visibility. (orig.)

  8. Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

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    Takayanagi, Yuki; Yoshida, Masahide; Takashima, Akihide; Takanami, Keiko; Yoshida, Shoma; Nishimori, Katsuhiko; Nishijima, Ichiko; Sakamoto, Hirotaka; Yamagata, Takanori; Onaka, Tatsushi

    2017-02-01

    Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  9. Gastric vagus mediates immobilization-induced hypocalcemia in rats.

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    Ma, J; Aou, S; Matsui, H; Hori, T

    1993-09-01

    The involvement of the parasympathetic nervous system in the etiology of stress-induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus.

  10. Secretin and autism: a basic morphological study about the distribution of secretin in the nervous system.

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    Köves, Katalin; Kausz, Mária; Reser, Diana; Illyés, György; Takács, József; Heinzlmann, Andrea; Gyenge, Eszter; Horváth, Károly

    2004-12-15

    For the first time, the relationship between secretin and autism has been demonstrated by one of us. Intravenous administration of secretin in autistic children caused a fivefold higher pancreaticobiliary fluid secretion than in healthy ones and, at least in some of the patients, better mental functions were reported after the secretin test. Because the precise localization of secretin in the brain is still not completely known, the abovementioned observation led us to map secretin immunoreactivity in the nervous system of several mammalian species. In the present work, the distribution of secretin immunoreactivity in cat and human nervous systems was compared with that of rats using an immunohistochemical approach. Secretin immunoreactivity was observed in the following brain structures of both humans and in colchicine-treated rats: (1) Purkinje cells in the cerebellar cortex; (2) central cerebellar nuclei; (3) pyramidal cells in the motor cortex; and (4) primary sensory neurons. Additionally, secretin immnoreactive cells were observed in the human hippocampus and amygdala and in third-order sensory neurons of the rat auditory system. In cats, secretin was only observed in the spinal ganglia. Our findings support the view that secretin is not only a gastrointestinal peptide but that it is also a neuropeptide. Its presence or the lack of its presence may have a role in the development of behavioral disorders.

  11. Origin of secretin receptor precedes the advent of tetrapoda: evidence on the separated origins of secretin and orexin.

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    Janice K V Tam

    Full Text Available At present, secretin and its receptor have only been identified in mammals, and the origin of this ligand-receptor pair in early vertebrates is unclear. In addition, the elusive similarities of secretin and orexin in terms of both structures and functions suggest a common ancestral origin early in the vertebrate lineage. In this article, with the cloning and functional characterization of secretin receptors from lungfish and X. laevis as well as frog (X. laevis and Rana rugulosa secretins, we provide evidence that the secretin ligand-receptor pair has already diverged and become highly specific by the emergence of tetrapods. The secretin receptor-like sequence cloned from lungfish indicates that the secretin receptor was descended from a VPAC-like receptor prior the advent of sarcopterygians. To clarify the controversial relationship of secretin and orexin, orexin type-2 receptor was cloned from X. laevis. We demonstrated that, in frog, secretin and orexin could activate their mutual receptors, indicating their coordinated complementary role in mediating physiological processes in non-mammalian vertebrates. However, among the peptides in the secretin/glucagon superfamily, secretin was found to be the only peptide that could activate the orexin receptor. We therefore hypothesize that secretin and orexin are of different ancestral origins early in the vertebrate lineage.

  12. Plasma levels of secretin in man and dogs: validation of a secretin radioimmunoassay

    International Nuclear Information System (INIS)

    Rayford, P.L.; Curtis, P.J.; Fender, H.R.; Thompson, J.C.

    1976-01-01

    We have developed and validated a secretin radioimmunoassay that is sufficiently sensitive to measure circulating levels of secretion in the plasma of man and dogs. At a final dilution of 1 : 50,000, the antibody bound 30 percent to 40 percent of radioiodinated ( 125 I) 6-tyrosyl synthetic secretin. Pure natural porcine secretin was used as a reference standard and a linear dose-response curve was generated with 10 to 1,000 pg. of the polypeptide. Little or no cross-reactivity was found when graded doses of other gastrointestinal polypeptides were assayed in the radioimmunoassay and immunoreactive secretin (IRS) in volumes of serum up to 300 μl could be measured accurately. Mean basal levels of IRS in the peripheral plasma of 22 normal human subjects was 216 +- 11.8 pg. per milliliter, in the peripheral plasma of dogs was 154 +- 6.1 pg. per milliliter, and in the portal plasma of dogs was 283 +- 22.2 pg. per milliliter. Basal IRS levels in portal plasma were significantly higher than in peripheral plasma (p < 0.05). In studies on the release of secretin in three normal human subjects, the mean basal level of secretin in peripheral plasma was 124 +- 8 pg. per milliliter. This level was increased to 137 +- 6, 137 +- 7, 149 +- 9, and 169 +- 10 pg. per milliliter during duodenal acidification with 0.15, 0.30, 0.77, and 1.25 mEq. 0.1N HCl per minute. The secretin response was related to the amount of acid used to irrigate the duodenum. In six dogs mean basal levels of secretin in the portal vein were 438 +- 102 pg. per milliliter. Secretin levels were significantly elevated above basal (p < 0.05) at 5, 10, 15, 20, 25, and 30 minutes during irrigation of the duodenum with 0.1N HCl and remained elevated for 5 and 10 minutes after duodenal acidification

  13. Secretin-radioimmunoassay, physiology and pathophysiology in man

    International Nuclear Information System (INIS)

    Haecki, W.H.

    1978-01-01

    Production of antibodies to secretin for radioimmunoassay is straightforward. Secretin is iodinated by weak oxydation with lactoperoxydase and subsequent purification by ionexchange chromatography (Sephadex C25). The specific activity of fresh label is between 650 and 900 mCi x mol -6 . The label is highly purified and may be used in radioimmunoassay for several months. In order to eliminate plasma interference sepharose-beads with covalently coupled secretin antibodies are used to produce secretin-free standard plasma samples. Delay in the separation of plasma from fresh blood samples can lead to erronous results, even to falsely elevated secretin levels. - Duo-denal acidification only leads to physiological increases of secretin plasma levels. This may happen by intraduodenal instillation of acid, or by an acidic oral drink, or to a lesser extent after a meal. Secretin is distributed throughout the plasma volume and has a short halflife of around 3 minutes. Impaired release of secretin is found in children with coeliac disease. The role of secretin in peptic ulcer however is not clear. Chronic pancreatitis and renal insufficiency are without effect on plasma secretin levels. (orig.) [de

  14. Functional MR-pancreatography with secretin - a comparison of imaging quality and diagnostic value pre and post secretin in the same patient

    International Nuclear Information System (INIS)

    Helmberger, H.; Hellerhoff, K.; Ruell, T.; Brandt, C.; Gerhardt, P.

    2000-01-01

    Purpose: The aim of the present study was to assess imaging improvement and diagnostic value of secretin stimulated MR-pancreatography (MRP) compared to conventional MRP. Materials and Methods: 50 patients were studied with a 1.0 T system using a single-shot-TSE sequence (RARE). Imaging quality and diameter of the different parts of the pancreatic tract and diagnoses were monitored before and after secretin. Results: The visualization of the normal main pancreatic duct (MPD) was improved significantly in head, body and tail. Side branches were not depicted at all. Even in chronic pancreatitis a significant improvement of imaging quality could be observed, but only in patients without duct dilation before secretin. In advanced disease with duct dilation, secretin stimulation provided no further diagnostic improvement. Conclusions: In conclusion, secretin increases the diagnostic value of MRP especially in patients with normal or non-dilated native MPD and may help to avoid unnecessary invasive procedures such as ERCP. (orig.) [de

  15. Secretin enhances [14C]erythritol clearance in unanesthetized dogs

    International Nuclear Information System (INIS)

    Lewis, M.H.; Baker, A.L.; Dhorajiwala, J.; Moossa, A.R.

    1982-01-01

    To determine the effect of secretin infusion on clearance of inert markers into bile, unanesthetized dogs fitted with Thomas cannulas received continuous infusions of [ 14 C]erythritol and [ 3 H]inulin throughout study. Taurocholic acid administered sequentially at 9.0, 20.0, and 40.0 mumol/min enhanced [ 14 C]erythritol clearance, and GIH secretin (3 units/min) administered along with TCA (40.0 mumol/min) increased [ 14 C]erythritol clearance from 4.9 +/- 1.2 ml/10 min to 6.8 +/- 1.3 ml/10 min (P less than 0.001), but simultaneously measured [ 3 H]inulin clearance was unaltered. Secretin alone also increased [ 14 C]erythritol clearance but did not alter [ 3 H]inulin clearance. The increase in [ 14 C]erythritol clearance per unit increase in bile flow was less during secretin infusion than TCA. Thus, secretin increases [ 14 C]erythritol transport through restricted channels, probably distal to the canaliculi. [ 14 C]Erythritol may not be an accurate marker for canalicular bile flow in dogs during secretin infusion

  16. Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

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    Tsai, Ching-Chung; Tey, Shu-Leei; Lee, Ming-Che; Liu, Ching-Wen; Su, Yu-Tsun; Huang, Shih-Che

    2018-04-01

    Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia. Copyright © 2018 Elsevier GmbH. All rights reserved.

  17. Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Okamoto, Taro; Fudaba, Yasuhiro; Ogundigie, P.S.; Ito, Akihiro

    1993-01-01

    The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3-day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidences of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X-rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)-positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P<0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP-positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value. (author)

  18. Secretin receptor involvement in prion-infected cells and animals.

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    Kimura, Tomohiro; Nishizawa, Keiko; Oguma, Ayumi; Nishimura, Yuki; Sakasegawa, Yuji; Teruya, Kenta; Nishijima, Ichiko; Doh-ura, Katsumi

    2015-07-08

    The cellular mechanisms behind prion biosynthesis and metabolism remain unclear. Here we show that secretin signaling via the secretin receptor regulates abnormal prion protein formation in prion-infected cells. Animal studies demonstrate that secretin receptor deficiency slightly, but significantly, prolongs incubation time in female but not male mice. This gender-specificity is consistent with our finding that prion-infected cells are derived from females. Therefore, our results provide initial insights into the reasons why age of disease onset in certain prion diseases is reported to occur slightly earlier in females than males. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Evaluation of dynamic MRCP after secretin stimulation for biliopancreatic diseases

    International Nuclear Information System (INIS)

    Ohhigashi, Seiji; Nishio, Takeki; Watanabe, Fumihiko; Haradome, Hiroki; Doi, Osamu

    2000-01-01

    Both pancreaticobiliary maljunction and pancreatogastrostomy after pancreatoduodenectomy were analyzed to assess the utility of dynamic MRCP after secretin stimulation. Dynamic MRCP obtained every 60 seconds for 15 minutes after secretin administration revealed the bile and pancreatic fluid kinetics. Calculating the intensity value from the MR images allowed objective estimation of the bile and pancreatic fluid kinetics. Thus, this study demonstrated that dynamic MRCP after secretin stimulation was significantly useful in evaluating not only the morphologic features in pancreaticobiliary maljunction but also pancreatic exocrine function after resection of the pancreas. (author)

  20. Secretin, its discovery, and the introduction of the hormone concept

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; de Muckadell, O B

    2000-01-01

    . The isolation and subsequent synthesis of secretin in the 1960s prepared the way for immunological techniques. Radioimmuno assays in the 1970s enabled demonstration of a direct endocrine role of secretin. Cloning and molecular hybridisation in the 1990s identified production site structure, precursor...

  1. Radioselenium pancreozymin-secretin test as a clinical test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Shichiri, M.; Etani, N.; Yoshida, M.; Harano, Y.; Hoshi, M.; Shigeta, Y.; Abe, H.

    1975-01-01

    The appearance of radioselenium in the protein fraction of duodenal aspirates has been studied after an intravenous injection of 75 Se-selenomethionine. The continuous flow of pancreatic juice was stimulated by pancreozymin at 120 minutes and by secretin at 140 minutes. A good distinction between normal subjects and patients with pancreatic disease was obtained by measuring 75 Se-radioactivity in the protein fraction of duodenal aspirates; either cumulative radioactivity during the combined 80-minute post-pancreozymin-secretin period, or maximum 75 Se-specific activity during the postsecretin period was used as an index. The test presented here might be a useful and sufficiently reliable method for detecting abnormal pancreatic exocrine function. This test can be performed along with the conventional pancreozymin-secretin test, serum enzyme response to pancreozymin and secretin, and pancreatic scintiscanning

  2. Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP

    International Nuclear Information System (INIS)

    Punwani, S.; Gillams, A.R.; Lees, W.R.

    2003-01-01

    Our objective was to quantify water volume using magnetic resonance cholangiopancreatography (MRCP) sequences and apply this to secretin-stimulated studies with the aim of quantifying pancreatic exocrine function. A commercially available single-shot MRCP sequence was used in conjunction with a body phased-array coil and a 1.5-T MR system. Signal intensity was measured in samples of water, pancreatic, duodenal juice, and secretin-stimulated pancreatic juice. A water phantom was made and MR calculated volumes compared with known water volumes within the phantom. Changes in small intestinal volume in response to secretin were measured in a group of 11 patients with no evidence of pancreatic disease. Changes in water volume were plotted over time. The pancreatic duct diameter before and after secretin was noted and filling defects were sought. All patients also underwent an axial breath-hold T1-weighted gradient-echo sequence and the pancreatic parenchyma was evaluated for size and signal intensity. There was no difference in the signal intensity of the different juice samples. There was excellent correlation between known and calculated MRCP volumes (χ 2 =0.99). All patients demonstrated normal duct morphology on MRCP and normal pancreatic parenchyma on T1-weighted imaging. The mean flow rate in the patient population was 8.1±2.5 ml/s over a median of 7 min (range 5-9 min). The MRCP sequence can be used to measure water volume. Sequential MRCP measurements following secretin permitted calculation of volume change and flow rate. This should prove useful as an indicator of pancreatic exocrine function. (orig.)

  3. Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in cultured guinea pig gastric mucosal cells.

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    Hoshino, Tatsuya; Takano, Tatsunori; Tomisato, Wataru; Tsutsumi, Shinji; Hwang, Hyun-Jung; Koura, Yuko; Nishimoto, Kiyo; Tsuchiya, Tomofusa; Mizushima, Tohru

    2003-01-01

    We previously reported that several gastric irritants, including ethanol, hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in cultured gastric mucosal cells. In the present study, we examined the effects of sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced necrosis in primary cultures of guinea pig gastric mucosal cells. The preincubation of cells with sucralfate was not necessary for its cytoprotective effect to be observed, thus making its mechanism of action different from that of other gastroprotective drugs. Necrosis of gastric mucosal cells induced by hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo can be explained, at least in part, by its inhibitory effect on gastric irritant-induced necrosis.

  4. Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man

    International Nuclear Information System (INIS)

    Nyberg, B.; Sonnenfeld, T.; Einarsson, K.

    1991-01-01

    The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion, bile volume increased by 60%, and during the combined VIP and secretin infursion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentration decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [ 14 C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.. 32 refs., 5 figs., 5 tabs

  5. Secretin-enhanced magnetic resonance cholangiopancreaticography: value for the diagnosis of chronic pancreatitis

    International Nuclear Information System (INIS)

    Heverhagen, J.T.; Burbelko, M.; Schenck zu Schweinsberg, T.; Funke, C.; Wecker, C.; Walthers, E.M.; Rominger, M.

    2007-01-01

    Endoscopic retrograde cholangiopancreaticography (ERCP) is the morphologic gold standard for the diagnosis of chronic pancreatitis. Magnetic Resonance Imaging (MRI) enables the visualization of not only the pancreatic duct but also the surrounding parenchyma using T2- and T1-weighted sequences before and after the application of a contrast agent. Moreover, it allows the depiction of ductal segments distal to a stenosis or occlusion. However, conventional Magnetic Resonance Cholangiopancreaticography (MRCP) was not able to achieve accuracy similar to that of ERCP. Despite many technological innovations, such as fast breath-hold acquisitions or respiratory-gated 3D sequences, this drawback could not be overcome. In recent years, secretin-enhanced MRCP has been used for the diagnosis of chronic pancreatitis. A recent study showed that secretin not only improves the visibility of the pancreatic duct and its side branches but it also enhances the diagnostic accuracy of MRCP. The sensitivity, specificity, and positive and negative predictive values were improved by the application of secretin. Moreover, the agreement between independent observers increased after the use of secretin. In addition, quantitative post-processing tools have been developed that enable the measurement of the exocrine pancreatic output non-invasively using secretin-enhanced MRCP. These tools facilitate applications, such as functional follow-up after pancreaticogastrostomy and pancreaticogastric anastomoses, evaluation of the functional status of the graft after pancreas transplantation and follow-up of pancreatic drainage procedures and duct disruption. (orig.)

  6. Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities.

    Science.gov (United States)

    Wang, Xiao-Yin; Yin, Jun-Yi; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2018-04-15

    The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1β in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Does secretin stimulation add to magnetic resonance cholangiopancreatography in characterising pancreatic cystic lesions as side-branch intraductal papillary mucinous neoplasm?

    International Nuclear Information System (INIS)

    Purysko, Andrei S.; Gandhi, Namita S.; Veniero, Joseph C.; Walsh, R.M.; Obuchowski, Nancy A.

    2014-01-01

    To assess the value of secretin during magnetic resonance cholangiopancreatography (MRCP) in demonstrating communication between cystic lesions and the pancreatic duct to help determine the diagnosis of side-branch intraductal papillary mucinous neoplasm (SB-IPMN). This is an IRB-approved, HIPAA-compliant retrospective study of 29 SB-IPMN patients and 13 non-IPMN subjects (control) who underwent secretin-enhanced MRCP (s-MRCP). Two readers blinded to the final diagnosis reviewed three randomised image sets: (1) pre-secretin HASTE, (2) dynamic s-MRCP and (3) post-secretin HASTE. Logistic regression, generalised linear models and ROC analyses were used to compare pre- and post-secretin results. There was no significant difference in median scores for the pre-secretin [reader 1: 1; reader 2: 2 (range -2 to 2)] and post-secretin HASTE [reader 1: 1; reader 2: 1 (range -2 to 2)] in the SB-IPMN group (P = 0.14), while the scores were lower for s-MRCP [reader 1: 0.5 (range -2 to 2); reader 2: 0 (range -1 to 2); P = 0.016]. There was no significant difference in mean maximum diameter of SB-IPMN on pre- and post-secretin HASTE, and s-MRCP (P > 0.05). Secretin stimulation did not add to MRCP in characterising pancreatic cystic lesions as SB-IPMN. (orig.)

  8. Identification of the gate regions in the primary structure of the secretin pIV.

    Science.gov (United States)

    Spagnuolo, Julian; Opalka, Natacha; Wen, Wesley X; Gagic, Dragana; Chabaud, Elodie; Bellini, Pierdomenico; Bennett, Matthew D; Norris, Gillian E; Darst, Seth A; Russel, Marjorie; Rakonjac, Jasna

    2010-04-01

    Secretins are a family of large bacterial outer membrane channels that serve as exit ports for folded proteins, filamentous phage and surface structures. Despite the large size of their substrates, secretins do not compromise the barrier function of the outer membrane, implying a gating mechanism. The region in the primary structure that forms the putative gate has not previously been determined for any secretin. To identify residues involved in gating the pIV secretin of filamentous bacteriophage f1, we used random mutagenesis of the gene followed by positive selection for mutants with compromised barrier function ('leaky' mutants). We identified mutations in 34 residues, 30 of which were clustered into two regions located in the centre of the conserved C-terminal secretin family domain: GATE1 (that spanned 39 residues) and GATE2 (that spanned 14 residues). An internal deletion constructed in the GATE2 region resulted in a severely leaky phenotype. Three of the four remaining mutations are located in the region that encodes the N-terminal, periplasmic portion of pIV and could be involved in triggering gate opening. Two missense mutations in the 24-residue region that separates GATE1 and GATE2 were also constructed. These mutant proteins were unstable, defective in multimerization and non-functional.

  9. Comparative studies of radioimmunologic serumtrypsin identifications and secretin-pancreozymin probe tests

    International Nuclear Information System (INIS)

    Scheithauer, R.

    1980-01-01

    In 29 patients with suspicion of a pancreatic disease, parallel to the classic secretin-pancreozymin test, the trypsin concentration was investigated basally and after stimulation by radioimmunological procedures. The basal mean value of the serum trypsin concentration was in those patients with sound pancreas 175 ng BIT/ml with limit values of 90 and 250 ng BIT/ml. The maximum value after stimulation was found in normal and pathologic cases 20 minutes after intravenous secretin administration (S 20), at most one sample earlier or later. The values ranged between 110 and 550 ng BIT/ml. The additional secretin-pancreozymin infusion did not lead to any further results. The quality investigation of the RIA in 9 cultures with 24 test sera showed in the lower measuring range a very high degree of liability (average concentration 188,7 ng BIT/ml) with a calculatory debit of 187,5 with maximum deviations of -17 and +25%, in the medium range they presented a sufficient liability, in high concentration dilution was necessary. The advantage of the tested procedure compared to the technically demanding SP test, i.e. the elimination of the deep sounding of the duodenum, has to be pointed out particularly. The discomfort for the patient is confined to two withdrawals of blood, basally and 20 minutes after exclusive secretin stimulation. (orig./MG) [de

  10. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al Asmari

    Full Text Available Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA, myeloperoxidase activity (MPO, expression of nuclear factor kappa B (NF-κB p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001 and acidity (P < 0.0001 and gastric ulcer index scores (P < 0.001. and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001 induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001, reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001. Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol.Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture. Keywords: Gastric ulcers, Pylorus ligation, Ethanol, Vanillin, Inflammation, Oxidative stress

  11. Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

    Science.gov (United States)

    Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

    2014-01-01

    The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

  12. Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

    Science.gov (United States)

    Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; Li, Jian H; Wess, Jürgen; Svelto, Maria

    2014-07-01

    X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

  13. Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts

    International Nuclear Information System (INIS)

    Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John; Takahashi, Naoki; Tamm, Eric P.; Mortele, Koenraad J.; Syngal, Sapna; Margolis, Daniel; Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I.; Kamel, Ihab R.

    2015-01-01

    Highlights: •Secretin improved visualization of ductal communication of a cystic pancreatic lesion. •No association between cysts and gender, ethnicity or type of high risk. •Incremental value of secretin could offset the added cost and time. -- Abstract: Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128 = 4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p = 0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p < 0.0005). Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions

  14. Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts

    Energy Technology Data Exchange (ETDEWEB)

    Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States); Takahashi, Naoki [Mayo Clinic (United States); Tamm, Eric P. [MD Anderson Cancer Center (United States); Mortele, Koenraad J. [Beth Israel Deaconess Medical Center (United States); Syngal, Sapna [Dana Farber Cancer Institute (United States); Margolis, Daniel [University of California, Los Angeles (United States); Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I. [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States); Kamel, Ihab R., E-mail: ikamel@jhmi.edu [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States)

    2015-04-15

    Highlights: •Secretin improved visualization of ductal communication of a cystic pancreatic lesion. •No association between cysts and gender, ethnicity or type of high risk. •Incremental value of secretin could offset the added cost and time. -- Abstract: Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128 = 4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p = 0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p < 0.0005). Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions.

  15. Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation

    International Nuclear Information System (INIS)

    Rocha, Barbara S.; Gago, Bruno; Barbosa, Rui M.; Laranjinha, Joao

    2009-01-01

    Nitrite, considered a biological waste and toxic product, is being regarded as an important physiological molecule in nitric oxide (·NO) biochemistry. Because the interaction of dietary phenolic compounds and nitrite would be kinetically (due to the high concentrations achieved) and thermodynamically (on basis of the redox potentials) feasible in the stomach, we have studied the potential reduction of nitrite by polyphenols present in several dietary sources. By measuring the time courses of ·NO production in simulated gastric juice (pH 2), the efficiency of the compounds studied is as follows: Epicatechin-3-O-gallate > quercetin > procyanidin B8 dimer > oleuropein > procyanidin B2 dimer > chlorogenic acid > epicatechin > catechin > procyanidin B5 dimer. The initial rates of ·NO production fall in a narrow range (ca. 1-5 μM s -1 ) but the distinct kinetics of the decay of ·NO signals suggest that competition reactions for ·NO are operative. The proof of concept that, in the presence of nitrite, phenol-containing dietary products induce a strong increase of ·NO in the stomach was established in an in vivo experiment with healthy volunteers consuming lettuce, onions, apples, wine, tea, berries and cherries. Moreover, selected mixtures of oleuropein and catechin with low nitrite (1 μM) were shown to induce muscle relaxation of stomach strips in a structure-dependent way. Data presented here brings strong support to the concept that polyphenols consumed in a variety of dietary products, under gastric conditions, reduce nitrite to ·NO that, in turn, may exert a biological impact as a local relaxant.

  16. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

    Science.gov (United States)

    Al Asmari, Abdulrahman; Al Shahrani, Hamoud; Al Masri, Nasser; Al Faraidi, Ahmed; Elfaki, Ibrahim; Arshaduddin, Mohammed

    2016-01-01

    Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion ( P  Vanillin significantly restored the depleted gastric wall mucus levels ( P  Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

  17. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    Science.gov (United States)

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

  18. Administration of secretin for autism alters dopamine metabolism in the central nervous system.

    Science.gov (United States)

    Toda, Yoshihiro; Mori, Kenji; Hashimoto, Toshiaki; Miyazaki, Masahito; Nozaki, Satoshi; Watanabe, Yasuyoshi; Kuroda, Yasuhiro; Kagami, Shoji

    2006-03-01

    We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.

  19. Protective effects of escin against indomethacin-induced gastric ulcer in mice.

    Science.gov (United States)

    Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

    2014-12-01

    Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.

  20. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

    Directory of Open Access Journals (Sweden)

    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  1. Motilin-induced gastric contractions signal hunger in man.

    Science.gov (United States)

    Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

    2016-02-01

    Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (phunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Repeatability and reliability of muscle relaxation properties induced by motor cortical stimulation.

    Science.gov (United States)

    Molenaar, Joery P; Voermans, Nicol C; de Jong, Lysanne A; Stegeman, Dick F; Doorduin, Jonne; van Engelen, Baziel G

    2018-03-15

    Impaired muscle relaxation is a feature of many neuromuscular disorders. However, there are few tests available to quantify muscle relaxation. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly inhibiting corticospinal drive. The aim of our study is to investigate if repeatability and reliability of TMS-induced relaxation is greater than voluntary relaxation. Furthermore, effects of sex, cooling and fatigue on muscle relaxation properties were studied. Muscle relaxation of deep finger flexors was assessed in twenty-five healthy subjects (14 M and 11 F, aged 39.1{plus minus}12.7 and 45.3{plus minus}8.7 years old, respectively) using handgrip dynamometry. All outcome measures showed greater repeatability and reliability in TMS-induced relaxation compared to voluntary relaxation. The within-subject coefficient of variability of normalized peak relaxation rate was lower in TMS-induced relaxation than in voluntary relaxation (3.0 vs 19.7% in men, and 6.1 vs 14.3% in women). The repeatability coefficient was lower (1.3 vs 6.1 s -1 in men and 2.3 vs 3.1 s -1 in women), and the intraclass correlation coefficient was higher (0.95 vs 0.53 in men and 0.78 vs 0.69 in women), for TMS-induced relaxation compared to voluntary relaxation. TMS enabled to demonstrate slowing effects of sex, muscle cooling, and muscle fatigue on relaxation properties that voluntary relaxation could not. In conclusion, repeatability and reliability of TMS-induced muscle relaxation was greater compared to voluntary muscle relaxation. TMS-induced muscle relaxation has the potential to be used in clinical practice for diagnostic purposes and therapy effect monitoring in patients with impaired muscle relaxation.

  3. Clinical role of secretin loading magnetic resonance cholangiopancreatography in the patients undergoing pancreatic resection

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Ken; Takahashi, Tsuyoshi; Yoshida, Muneki; Kakita, Akira [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine

    2002-01-01

    We determined factors contributing to increased signal intensity in the reconstructed jejunal loop in patients undergoing pancreatic resection, frequently observed on magnetic resonance cholangiopancreatography following intravenous injection of secretin (S/MRCP). We also evaluated the possible roles of S/MRCP in assessing the patency of pancreatojejunal anastomosis and the secretory function of the remnant pancreas. Subject were 44 patients undergoing several types of pancreatic resection. Baseline output and response to secretin of the remnant pancreas were measured after surgery. S/MRCP and pancreatic function diagnostant (PFD) tests were conducted preoperatively, and in early and late periods after surgery. Baseline pancreatic output was 1.2{+-}0.7 ml/10-min, and increased after secretin load to a maximum 9.0{+-}6.6 ml/10-min in 10 min. Signal intensity of the jejunal loop increased in 2 patients versus 40 patients (95%) during the early versus late postoperative periods. During the late period, PFD was significantly higher in patients with increased signal intensity than in those without. PFD correlated well with cumulative pancreatic output following secretin loading (r=0.820). A major factor responsible for increased signal intensity in S/MRCP of the jejunal loop was increased pancreatic output. The increase in signal intensity was a definitive sign of patent pancreatojejunal anastomosis. S/MRCP thus seems to have a potential for evaluating the secretory function of the remnant pancreas. (author)

  4. Clinical role of secretin loading magnetic resonance cholangiopancreatography in the patients undergoing pancreatic resection

    International Nuclear Information System (INIS)

    Shimada, Ken; Takahashi, Tsuyoshi; Yoshida, Muneki; Kakita, Akira

    2002-01-01

    We determined factors contributing to increased signal intensity in the reconstructed jejunal loop in patients undergoing pancreatic resection, frequently observed on magnetic resonance cholangiopancreatography following intravenous injection of secretin (S/MRCP). We also evaluated the possible roles of S/MRCP in assessing the patency of pancreatojejunal anastomosis and the secretory function of the remnant pancreas. Subject were 44 patients undergoing several types of pancreatic resection. Baseline output and response to secretin of the remnant pancreas were measured after surgery. S/MRCP and pancreatic function diagnostant (PFD) tests were conducted preoperatively, and in early and late periods after surgery. Baseline pancreatic output was 1.2±0.7 ml/10-min, and increased after secretin load to a maximum 9.0±6.6 ml/10-min in 10 min. Signal intensity of the jejunal loop increased in 2 patients versus 40 patients (95%) during the early versus late postoperative periods. During the late period, PFD was significantly higher in patients with increased signal intensity than in those without. PFD correlated well with cumulative pancreatic output following secretin loading (r=0.820). A major factor responsible for increased signal intensity in S/MRCP of the jejunal loop was increased pancreatic output. The increase in signal intensity was a definitive sign of patent pancreatojejunal anastomosis. S/MRCP thus seems to have a potential for evaluating the secretory function of the remnant pancreas. (author)

  5. Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Engjom, Trond; Dimcevski, Georg; Tjora, Erling; Wathle, Gaute; Erchinger, Friedemann; Laerum, Birger N.; Gilja, Odd H.; Haldorsen, Ingfrid Salvesen

    2018-01-01

    Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF). We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase. Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56-0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure. Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion. (orig.)

  6. Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

    Science.gov (United States)

    Tsai, Chung-Lin; Chiu, Ying-Ming; Ho, Tin-Yun; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Wu, Yi-Ying

    2018-04-01

    Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. These results suggest that gallic acid has a potential role in the treatment of gastric cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  8. Gastric injury induced by hemorrhage, local ischemia, and oxygen radical generation

    International Nuclear Information System (INIS)

    Wadhwa, S.S.; Perry, M.A.

    1987-01-01

    Gastric mucosal injury caused by local intra-arterial generation of oxygen-derived free radicals was compared with gastric injury caused by 30 min of hemorrhage-induced ischemia or local ischemia. The index of injury was the loss of 51 Cr-labeled red cells across the gastric mucosa. Generation of oxygen radicals in the celiac artery caused a rapid increase in mucosal blood loss during the period of radical generation, and this loss was maintained after radical production ceased. Local ischemia produced similar mucosal injury; however, this occurred after reperfusion of the stomach and not during the ischemic episode. Hemorrhage-induced ischemia produced a threefold greater mucosal blood loss than local ischemia. The results of this study indicate that (1) oxygen radicals generated enzymatically in the blood supply to the stomach cause mucosal bleeding of similar magnitude to that observed after local ischemia and (2) that gastric ischemia induced by systemic hypotension produces more severe gastric injury than the same level of local hypotension

  9. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

    Science.gov (United States)

    Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

    2005-01-01

    AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

  10. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    International Nuclear Information System (INIS)

    Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

    2013-01-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue

  11. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  12. Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System

    OpenAIRE

    Gu, Shuang; Rehman, Saima; Wang, Xiaohui; Shevchik, Vladimir E.; Pickersgill, Richard W.

    2012-01-01

    Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this pr...

  13. Fasting does not induce gastric emptying in rats.

    Science.gov (United States)

    Brito, Marcus Vinicius Henriques; Yasojima, Edson Yuzur; Teixeira, Renan Kleber Costa; Houat, Abdallah de Paula; Yamaki, Vitor Nagai; Costa, Felipe Lobato da Silva

    2015-03-01

    To evaluate the effect of fasting on gastric emptying in mice. Twenty-eight mice were distributed into three study groups: a normal group (N=4): normal standard animals; a total fasting group (N=12): subjected to food and water deprivation and a partial fasting group (N=12): subjected to food deprivation only. The fasting groups were subdivided into three subgroups of four animals each, according to the date of euthanasia: 24, 48 and 72 hours. Was analyzed: the gastric volume, degree of the gastric wall distention and the presence of food debris in gastrointestinal tract. The mean gastric volume was 1601 mm3 in the normal group, 847 mm3 in total fasting group and 997 mm3 in partial fasting group. There was difference between the fasting groups in any analyzed period (pfasting (p>0.05). Total fasting or only-solids deprivation does not induce gastric emptying in mice.

  14. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

    LENUS (Irish Health Repository)

    Murphy, D B

    2012-02-03

    BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg\\/kg morphine, or 0.09 mg\\/kg morphine plus 0.3 mg\\/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +\\/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +\\/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +\\/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +\\/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is

  15. Honey potentiates the gastric protection effects of sucralfate against ammonia-induced gastric lesions in rats.

    Science.gov (United States)

    Ali, Abu Taib Mohammad Mobarok; Al Swayeh, Othman Abdullah

    2003-09-01

    Natural honey is widely used all over the world as a complementary and alternative medicine in various disorders including gastrointestinal lesions. To evaluate the effects of combination of low dosage of honey (0.312 g/kg) and sucralfate (0.125 or 0.250 g /kg) on gastric protection and to determine any potentiating interactions between them against ammonia-induced gastric lesions in rats. Twenty-four hours fasted rats were given I ml of ammonium hydroxide 1 % intragastrically and they were killed one hour later under deep ether anesthesia. The gastric lesion index was calculated according to the method of Takaishi et al 1998. Non protein sulthydryls level was determined spectrophotometrically as described by Sedlak and Lindsay 1968. Administration of ammonium hydroxide produced red and black linear lesions and significant depletion of gastric nonprotein sulthydryls level. Oral administration of honey (0.312g/kg) or sucralfate (0.125 and 0.250 g/kg) 30 min before ammonium hydroxide reduced the severity of gastric mucosal lesions by 1 I or 18 and 42 % respectively, and has shown the changes in nonprotein sulfhydryls level induced by ammonium hydroxide. Furthermore, pretreatment with a combination of a low dose of honey (0.312 g /kg) and sucralfate (0.125 g or 0.250 g/kg) afforded significantly greater protection (58 and 77 %) than that obtained with either of them administered alone. The present results suggest potentiation of gastric protection effect of sucralfate by honey and this may have a clinical value in the treatment of peptic ulcer diseases in Helicobacter pylori positive patients.

  16. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    Science.gov (United States)

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

  17. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

  18. Santorinicele: secretin-enhanced magnetic resonance cholangiopancreatography findings before and after minor papilla sphincterotomy

    Energy Technology Data Exchange (ETDEWEB)

    Boninsegna, Enrico; Manfredi, Riccardo; Ventriglia, Anna; Negrelli, Riccardo; Pedrinolla, Beatrice; Mehrabi, Sara; Pozzi Mucelli, Roberto [University of Verona, Department of Radiology - Policlinico G.B. Rossi, Verona (Italy); Gabbrielli, Armando [University of Verona, Department of Medicine - Policlinico G.B. Rossi, Verona (Italy)

    2015-08-15

    To evaluate secretin-enhanced MRCP (S-MRCP) findings of patients with pancreas divisum and Santorinicele, before and after minor papilla sphincterotomy. S-MRCP examinations of 519 patients with suspected pancreatic disease were included. Size of the main pancreatic duct, presence and calibre of Santorinicele were evaluated. Duodenal filling was assessed on dynamic images. After sphincterotomy the same parameters and the clinical findings were re-evaluated. Pancreas divisum was depicted in 55/519 patients (11 %) by MRCP and an additional 26/519 by S-MRCP (total 81/519, 16 %). Santorinicele was detected in 7/81 patients (8.6 %) with pancreas divisum by MRCP and an additional 20/81 by S-MRCP (total 27/81, 33 %). Dorsal duct in patients with Santorinicele was significantly larger in the head compared with patients with only pancreas divisum (p < 0.01), in basal conditions (average 2.4 versus 1.9 mm) and after secretin administration (average 3.0 versus 2.4 mm). Duodenal filling was impaired in 11/27 patients (41 %) with Santorinicele. After sphincterotomy significant reduction in size of Santorinicele (-33 %) and dorsal duct (-17 %), increase of pancreatic juice and symptoms improvement were observed. Secretin administration increases the accuracy of MRCP in detecting Santorinicele and demonstrates the impaired duodenal filling. S-MRCP is useful to assess results of sphincterotomy. (orig.)

  19. Irradiation-induced stress relaxation of Eurofer97 steel

    International Nuclear Information System (INIS)

    Luzginova, N.V.; Jong, M.; Rensman, J.W.; Hegeman, J.B.J.; Laan, J.G. van der

    2011-01-01

    The irradiation-induced stress relaxation behavior of Eurofer97 at 300 deg. C up to 3.4 dpa and under pre-stress loads typical for the ITER applications is investigated. The bolt specimens are pre-loaded from 30% to 90% of the yield strength. To verify the results obtained with the pre-stressed bolts, bent strips were investigated as well. The strips are bent into a pre-defined radius in order to achieve similar pre-stress levels. The irradiation-induced stress relaxation is found to be independent of the pre-stress level. 10-12% of the stress relaxation in Eurofer97 may be reached after a dose of 0.1 dpa, and after an irradiation dose of 2.7 dpa 42-47% of the original pre-stress is retained.

  20. Sensitivity and Specificity of Hypnosis Effects on Gastric Myoelectrical Activity

    Science.gov (United States)

    Enck, Paul; Weimer, Katja; Muth, Eric R.; Zipfel, Stephan; Martens, Ute

    2013-01-01

    Objectives The effects of hypnosis on physiological (gastrointestinal) functions are incompletely understood, and it is unknown whether they are hypnosis-specific and gut-specific, or simply unspecific effects of relaxation. Design Sixty-two healthy female volunteers were randomly assigned to either a single session of hypnotic suggestion of ingesting an appetizing meal and an unappetizing meal, or to relax and concentrate on having an appetizing or unappetizing meal, while the electrogastrogram (EGG) was recorded. At the end of the session, participants drank water until they felt full, in order to detect EGG-signal changes after ingestion of a true gastric load. During both conditions participants reported their subjective well-being, hunger and disgust at several time points. Results Imagining eating food induced subjective feelings of hunger and disgust as well as changes in the EGG similar to, but more pronounced than those seen with a real gastric water load during both hypnosis and relaxation conditions. These effects were more pronounced when imagining an appetizing meal than with an unappetizing meal. There was no significant difference between the hypnosis and relaxation conditions. Conclusion Imagination with and without hypnosis exhibits similar changes in subjective and objective measures in response to imagining an appetizing and an unappetizing food, indicating high sensitivity but low specificity. PMID:24358287

  1. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  2. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

    Directory of Open Access Journals (Sweden)

    Maulik N Gandhi

    2012-06-01

    Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

  3. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

    2014-01-01

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  4. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  5. Resonant tunneling measurements of size-induced strain relaxation

    Science.gov (United States)

    Akyuz, Can Deniz

    Lattice mismatch strain available in such semiconductor heterostructures as Si/SiGe or GaAs/AlGaAs can be employed to alter the electronic and optoelectronic properties of semiconductor structures and devices. When deep submicron structures are fabricated from strained material, strained layers relax by sidewall expansion giving rise to size- and geometry-dependent strain gradients throughout the structure. This thesis describes a novel experimental technique to probe the size-induced strain relaxation by studying the tunneling current characteristics of strained p-type Si/SiGe resonant tunneling diodes. Our current-voltage measurements on submicron strained p-Si/SiGe double- and triple-barrier resonant tunneling structures as a function of device diameter, D, provide experimental access to both the average strain relaxation (which leads to relative shifts in the tunneling current peak positions) and strain gradients (which give rise to a fine structure in the current peaks due to inhomogeneous strain-induced lateral quantization). We find that strain relaxation is significant, with a large fraction of the strain energy relaxed on average in D ≤ 0.25 m m devices. Further, the in-plane potentials that arise from inhomogeneous strain gradients are large. In the D ˜ 0.2 m m devices, the corresponding lateral potentials are approximately parabolic exceeding ˜ 25 meV near the perimeter. These potentials create discrete hole states in double-barrier structures (single well), and coupled hole states in triple-barrier structures (two wells). Our results are in excellent agreement with finite-element strain calculations in which the strained layers are permitted to relax to a state of minimum energy by sidewall expansion. Size-induced strain relaxation will undoubtedly become a serious technological issue once strained devices are scaled down to the deep submicron regime. Interestingly, our calculations predict and our measurements are consistent with the appearance of

  6. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ayşin Akıncı; Mukaddes Eşrefoğlu; Elif Taşlıdere; Burhan Ateş

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino...

  7. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ak?nc?, Ay?in; E?refo?lu, Mukaddes; Ta?l?dere, Elif; Ate?, Burhan

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation Methods: Forty male Wistar albino rats were...

  8. Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

    2012-09-01

    What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

  9. Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

    Science.gov (United States)

    Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

    2006-12-01

    We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

  10. Influence of ondansetron on gastric sensorimotor responses to short duodenal acid infusion in healthy volunteers.

    Science.gov (United States)

    Vanuytsel, T; Karamanolis, G; Van Oudenhove, L; Oudenhove, L V; Vos, R; Tack, J

    2011-03-01

    Duodenal acid infusion induces gastric relaxation and sensitization to distension in healthy volunteers. The acid-sensitive mechanism is still unknown. We hypothesized that 5HT(3)-blockade can inhibit the acid-induced duodenogastric sensorimotor reflex in healthy volunteers. Fourteen healthy volunteers were included in a randomized, double-blind placebo-controlled cross-over trial. An infusion tube with attached pH-electrode was positioned in the duodenum and a barostat balloon was located in the gastric fundus. Proximal gastric volume and sensitivity to distension were assessed before and during duodenal acid infusion and after pretreatment with intravenous (i.v.) ondansetron (a 5HT(3)-receptor antagonist, 8 mg) or saline. An overall perception score (0-6) and an assessment of nine dyspeptic symptoms by visual analogue scales (VAS) were obtained. Results are given as mean ± SEM. Ondansetron had no effect on duodenal pH and on the acid-induced increase of proximal gastric volume (increase of 80 ± 20 vs 83 ± 15 mL after ondansetron and placebo; effect of acid acid infusion and gastric distension. 5HT(3)-receptors are involved in acid-induced duodenogastric sensitization, but not in the duodenogastric inhibitory motor reflex. © 2010 Blackwell Publishing Ltd.

  11. 3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells.

    Science.gov (United States)

    Ye, Yang; Miao, Shuhan; Wang, Yan; Zhou, Jianwei; Lu, Rongzhu

    2015-05-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co-treatment with TRAIL (25 or 50 ng/ml) and DIM (10 µmol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms.

  12. A study of the effect of propolis against gastric ulcers induced in gamma -irradiated rats

    International Nuclear Information System (INIS)

    Abd El-Aziz, R.R

    2009-01-01

    The anti-ulcerogenic activity of propolis or bee glue, a natural product from honey bees, was investigated against indomethacin -induced gastric ulcers in non- irradiated and irradiated rats, and the effects were compared with those of the proton pump inhibitor lansoprazole, as a reference anti-ulcerogenic drug. Indomethacin-induced gastric ulcer was used in this study as a model of experimentally induced gastric ulceration. The anti-ulcerogenic, antisecretory and cytoprotective activities of 13% aqueous propolis extract (APE) were assessed. Gastric contents of animals were sampled for the measurement of free acidity, acid output, mucin and pepsin concentrations in the gastric juice. The stomach was examined macroscopically for the determination of the ulcer index. PGE 2 was assayed in the gastric mucosa, while the pro-inflammatory cytokines TNF-α and IL-1β as well as the oxidative stress marker MDA were determined in the plasma.

  13. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  14. Fetal responses to induced maternal relaxation during pregnancy

    OpenAIRE

    DiPietro, Janet A.; Costigan, Kathleen A.; Nelson, Priscilla; Gurewitsch, Edith D.; Laudenslager, Mark L.

    2007-01-01

    Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-minute guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal...

  15. Induced pneumoperitoneum in spiral CT evaluation of gastric cancer

    International Nuclear Information System (INIS)

    Guo Hua; Gao Jianbo; Li Yintai; Yang Xuehua; Chen Xuejun; Guan Sheng

    2001-01-01

    Objective: To evaluate the diagnostic value and clinical significance of preoperative staging in gastric cancer with induced pneumoperitoneum in spiral CT (SCTPP). Methods: Both routine SCT and SCTPP were performed in 52 lean patients suffered from gastric cancers, and comparison was made between SCT findings and surgical and histopathologic findings. Results: The accuracy of routine SCT and SCTPP in determining the T-staging was 72% and 96%, respectively (x 2 = 8.0, P 2 = 0.006, P > 0.05). The sensitivity in determining M-staging was 61% and 100%, respectively (x 2 = 0.04, P 2 6.03, P < 0.05). Conclusion: The accuracy of SCTPP in determining preoperative staging of gastric cancer was significantly higher than that of routine SCT. SCTPP has important guiding significance for the selection of the treatment strategy in gastric cancer

  16. The effects of synthetic human secretin on calcium carbonate solubility in human bile.

    Science.gov (United States)

    Knyrim, K; Vakil, N

    1990-11-01

    This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for

  17. Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

    Science.gov (United States)

    Li, Weifeng; Wang, Yu; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Niu, Xiaofeng

    2017-04-01

    The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  18. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Pan, Charlie C. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Amarnath, Sudha [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Ensminger, William D. [Department of Internal Medicine, Division of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Lawrence, Theodore S.; Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

    2012-09-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  19. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    International Nuclear Information System (INIS)

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-01-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD 50 (normal) = 56 Gy and TD 50 (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD 50 value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  20. Gastroprotective effect of garlic in indomethacin induced gastric ulcer in rats.

    Science.gov (United States)

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Selim, Hend M

    2016-01-01

    Garlic, in its natural plant state, has a great history in ancient medicine as a remedy for many diseases. In our study, the gastroprotective effect of aged garlic extract (AGE) and the possible underlying mechanisms were investigated in an experimental model of indomethacin-induced gastric ulcer. Male Wistar rats were divided into four groups: (normal control, n = 20), ulcer control (indomethacin group, n = 20), (omeprazole group, n = 30) and (garlic group, n = 20). Each dose of garlic and omeprazole was given to rats orally daily for 10 consecutive days before induction of ulcer by indomethacin. Indomethacin was given as a single oral dose (100 mg/kg). Four hours later after indomethacin treatment, the rats were sacrificed and gastric tissue was obtained for histopathological examination, calculation of ulcer index and measurement of oxidative stress markers as well as gastroprotective mediators. The results showed that indomethacin induced gastric ulcer (ulcer index = 2900), was associated with a significant increase of tumor necrosis factor-alpha and malondialdehyde, and significant decrease of the gastroprotective mediators prostaglandin E2, glutathione (GSH) and nitric oxide (NO) compared with normal control. Pretreatment with AGE produced comparable results with those obtained in the omeprazole group; the preventive index in the AGE group was 83.4% compared with 94.5% in the omeprazole group. The prophylactic role of AGE in indomethacin-induced ulcer was, in part, mediated by decreasing oxidative stress and increasing gastric level of PGE2, GSH, and NO. AGE corrected the histopathological abnormalities in gastric tissue and proved a promising gastroprotective role in gastric ulcer. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.

    Science.gov (United States)

    Chandranath, S I; Bastaki, S M A; D'Souza, A; Adem, A; Singh, J

    2011-03-01

    Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

  2. Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

    Science.gov (United States)

    Sai, Jin-Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio

    2008-02-28

    To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

  3. Peroxynitrite-induced relaxation in isolated rat aortic rings and mechanisms of action

    International Nuclear Information System (INIS)

    Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

    2005-01-01

    The present study was designed to evaluate the effects of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOO - (from 10 -8 to 10 -4 M) failed to alter the basal tension. In phenylephrine (PE; 5 x 10 -7 M)-precontracted rat aortic rings (RAR), ONOO - elicited concentration-dependent relaxation at concentrations of from 10 -8 to 10 -4 M. The effective concentrations producing approximately 50% of maximal relaxation (ED 5 ) to ONOO - were 1.84 x 10 -5 M and 1.96 x 10 -5 M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Sildenafil (10 -7 M), on the other hand, significantly potentiated the ONOO - -induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOO - -induced relaxation in a dose-dependent manner. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOO - on RAR. Our new results suggest that ONOO - -triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K + -channel activation, activation of myosin phosphatase activity, and

  4. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    Minkyung Bae

    2014-01-01

    Full Text Available Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL-8 and inducible nitric oxide synthase (iNOS, which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO and increased activity of myeloperoxidase (MPO, a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog, IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB; and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS, MPO activity, and LPO level in H. pylori-infected gastric mucosa.

  5. Anti-inflammatory Activities and Gastric Ulcer-inducing Properties of Tetraacetylquercetin and Tetrapivaloylquercetin

    Directory of Open Access Journals (Sweden)

    Rina Herowati

    2016-12-01

    Full Text Available Quercetin (3,3’4’,5,7-pentahydroxyflavone has been reported to show anti-inflammatory activity. However, its low oral bioavailability limits the application of quercetin in therapy. Ester derivatives of quercetin have been reported to have higher bioavailability than quercetin. This research aimed to study the anti-inflammatory activities and gastric ulcer-inducing properties of tetraacetylquercetinas well as tetrapivaloylquercetin. Synthesis of tetra-acyl derivatives of quercetin was conducted using acetic anhydride or pivaloyl chloride in the presence of pyridine and the structure was confirmed by 1H-NMR and 13C-NMR spectroscopy as well as elemental analysis. At a dose of 20 mg/kg bw, oral administration of quercetin only showed 20% inhibition activity on carragenan induced rat paw edema, while tetraacetyl and tetrapivaloyl derivatives at equimolar dose showed 11-33% and 5-15% inhibition activity respectively. Contrary to the gastric ulcer healing-promoting action of quercetin, tetraacetylquercetin caused mild gastric ulcers. However, no gastric ulcer was observed after administration of tetrapivaloylquercetin. It was concluded that acylation enhances the anti-inflammatory activity of quercetin but causes mild gastric ulcers in the case of tetraacetylation.

  6. Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

    Science.gov (United States)

    Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

    2016-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats.

    Science.gov (United States)

    Seto, Yasuhiro; Yoshida, Naoyuki; Kaneko, Hiroshi

    2011-01-01

    Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloon gastric distension to enable abdominal muscle contractions and characterized the visceromotor response (VMR) to such distension in conscious rats. We also investigated the effects of mosapride on gastric distension-induced VMR in the same model. Mosapride (3-10 mg/kg, p.o.) dose-dependently inhibited gastric distension-induced VMR in rats. However, itopride even at 100 mg/kg failed to inhibit gastric distension-induced VMR in rats. Additionally, a major metabolite M1 of mosapride, which possesses 5-HT(3)-receptor antagonistic activity, inhibited gastric distension-induced VMR. The inhibitory effect of mosapride on gastric distension-induced visceral pain was partially, but significantly inhibited by SB-207266, a selective 5-HT(4)-receptor antagonist. This study shows that mosapride inhibits gastric distension-induced VMR in conscious rats. The inhibitory effect of mosapride is mediated via activation of 5-HT(4) receptors and blockage of 5-HT(3) receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.

  8. (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels.

    Science.gov (United States)

    Marinko, Marija; Jankovic, Goran; Nenezic, Dragoslav; Milojevic, Predrag; Stojanovic, Ivan; Kanjuh, Vladimir; Novakovic, Aleksandra

    2018-02-01

    In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K + channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K + , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca 2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K V channels, BK Ca channels, and at least partly, K ATP channels. In addition, not only the inhibition of extracellular Ca 2+ influx, but regulation of the intracellular Ca 2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca 2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Characterization of 5-hydroxytryptamine-induced contraction and acetylcholine-induced relaxation in isolated chicken basilar artery.

    Science.gov (United States)

    Matsumoto, F; Watanabe, Y; Obi, T; Islam, M Z; Yamazaki-Himeno, E; Shiraishi, M; Miyamoto, A

    2012-05-01

    The aim of the present study was to clarify the responsiveness of the chicken basilar artery to 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and to characterize the related receptor subtypes in vitro. Basilar arteries were obtained from freshly slaughtered broiler chickens. The 5-HT induced concentration-dependent contraction of the arteries. The concentration-response curves for 5-HT were shifted 30-fold to the right by methiothepin (a 5-HT(1) and 5-HT(2) receptor antagonist) and 3-fold to the right by ketanserin (a 5-HT(2) receptor antagonist). In the presence of ketanserin, the concentration-response curve for 5-HT was shifted 10-fold to the right by methiothepin. The pA(2) value for methiothepin was 8.26. The ACh induced concentration-dependent relaxation under conditions of precontraction by 5-HT. The concentration-response curve for ACh was shifted to the right by atropine [a nonselective muscarinic (M) receptor antagonist] and hexahydro-sila-difenidol hydrochloride, a p-fluoroanalog (pFHHSiD, an M(3) receptor antagonist), but not by pirenzepine (an M(1) receptor antagonist) or methoctramine (an M(2) receptor antagonist). The pA(2) value for pFHHSiD was 7.55. Nω-Nitro-l-arginine (a nitric oxide synthase inhibitor) inhibited ACh-induced relaxation by approximately 50%. These results suggest that 5-HT induces contraction via activation of 5-HT(1) and 5-HT(2) receptors and that ACh induces relaxation via activation of the M(3) receptor. The 5-HT(1) receptor might play a dominant role in 5-HT-induced contraction. One of the factors involved in ACh-induced relaxation is probably nitric oxide released from endothelial cells.

  10. Successful treatment with a combination of endoscopic injection and irrigation with coca cola for gastric bezoar-induced gastric outlet obstruction.

    Science.gov (United States)

    Lin, Chen-Sheng; Tung, Chun-Fang; Peng, Yen-Chun; Chow, Wei-Keung; Chang, Chi-Sen; Hu, Wei-Hsiung

    2008-01-01

    We report a case of gastric bezoar-induced gastric outlet obstruction that was successfully treated with a combination of endoscopic injection and irrigation with Coca Cola. A 73-year-old diabetic woman had a history of perforated peptic ulcer and had received pyloroplasty more than 20 years previously. She had been ingesting Pho Pu Zi (Cordia dichotoma Forst. f.) as an appetizer for 1 month. She presented with epigastric pain, nausea, and vomiting. Upper gastrointestinal endoscopy, performed at a local hospital, showed 2 gastric bezoars in the stomach, and 1 of them impacted at the pylorus. She was referred to our emergency department for removal of the gastric bezoars that were suspected to be causing gastric outlet obstruction. All attempts at endoscopic removal using a polypectomy snare, biopsy forceps and Dormia basket failed. We then injected Coca Cola directly into the bezoar mass, followed by irrigation with Coca Cola. Follow-up endoscopy was performed the next day, which revealed that the gastric bezoars had dissolved spontaneously.

  11. Protective effect of bovine milk against HCl and ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Yoo, Jeong-Hyun; Lee, Jeong-Sang; Lee, You-Suk; Ku, SaeKwang; Lee, Hae-Jeung

    2018-05-01

    The purpose of this study was to investigate the gastroprotective effects of bovine milk on an acidified ethanol (HCl-ethanol) mixture that induced gastric ulcers in a mouse model. Mice received different doses of commercial fresh bovine milk (5, 10, and 20 mL/kg of body weight) by oral gavage once a day for 14 d. One hour after the last oral administration of bovine milk, the HCl-ethanol mixture was orally intubated to provoke severe gastric damage. Our results showed that pretreatment with bovine milk significantly suppressed the formation of gastric mucosa lesions. Pretreatment lowered gastric myeloperoxidase and increased gastric mucus contents and antioxidant enzymes catalase and superoxide dismutase. Administration of bovine milk increased nitrate/nitrite levels and decreased the malondialdehyde levels and the expression of proinflammatory genes, including transcription factor nuclear factor-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the stomach of mice. These results suggest that bovine milk can prevent the development of gastric ulcer caused by acid and alcohol in mice. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

    OpenAIRE

    Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

    1989-01-01

    1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

  13. Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

    Science.gov (United States)

    Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

    2017-01-01

    Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Jae-Heung Park

    2015-03-01

    Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

  15. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  16. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

    2012-01-01

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  17. Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries

    Science.gov (United States)

    Glusa, Erika; Adam, Christine

    2001-01-01

    Serine proteinases elicit profound cellular effects in various tissues mediated by activation of proteinase-activated receptors (PAR). In the present study, we investigated the vascular effects of cathepsin G, a serine proteinase that is present in the azurophil granules of leukocytes and is known to activate several cells that express PARs. In prostaglandin F2α (3 μM)-precontracted rings from porcine pulmonary arteries with intact endothelium, cathepsin G caused concentration-dependent relaxant responses (pEC50=9.64±0.12). The endothelium-dependent relaxant effect of cathepsin G could also be demonstrated in porcine coronary arteries (pEC50=9.23±0.07). In pulmonary arteries the cathepsin G-induced relaxation was inhibited after blockade of nitric oxide synthesis by L-NAME (200 μM) and was absent in endothelium-denuded vessels. Bradykinin- and cathepsin G-induced relaxant effects were associated with a 5.7 fold and 2.4 fold increase in the concentration of cyclic GMP, respectively. Compared with thrombin and trypsin, which also produced an endothelium-dependent relaxation in pulmonary arteries, cathepsin G was 2.5 and four times more potent, respectively. Cathepsin G caused only small homologous desensitization. In cathepsin G-challenged vessels, thrombin was still able to elicit a relaxant effect. The effects of cathepsin G were blocked by soybean trypsin inhibitor (IC50=0.043 μg ml−1), suggesting that proteolytic activity is essential for induction of relaxation. Recombinant acetyl-eglin C proved to be a potent inhibitor (IC50=0.14 μg ml−1) of the cathepsin G effect, whereas neither indomethacin (3 μM) nor the thrombin inhibitor hirudin (5 ATU ml−1) elicited any inhibitory activity. Due to their polyanionic structure defibrotide (IC50=0.11 μg ml−1), heparin (IC50=0.48 μg ml−1) and suramin (IC50=1.85 μg ml−1) diminished significantly the relaxation in response to the basic protein cathepsin G. In conclusion, like

  18. Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

    Science.gov (United States)

    Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

    1989-07-01

    1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

  19. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

    Science.gov (United States)

    Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

    2008-03-01

    Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

  20. Successful Treatment with a Combination of Endoscopic Injection and Irrigation with Coca Cola for Gastric Bezoar-induced Gastric Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Chen-Sheng Lin

    2008-01-01

    Full Text Available We report a case of gastric bezoar-induced gastric outlet obstruction that was successfully treated with a combination of endoscopic injection and irrigation with Coca Cola. A 73-year-old diabetic woman had a history of perforated peptic ulcer and had received pyloroplasty more than 20 years previously. She had been ingesting Pho Pu Zi (Cordia dichotoma Forst. f. as an appetizer for 1 month. She presented with epigastric pain, nausea, and vomiting. Upper gastrointestinal endoscopy, performed at a local hospital, showed 2 gastric bezoars in the stomach, and 1 of them impacted at the pylorus. She was referred to our emergency department for removal of the gastric bezoars that were suspected to be causing gastric outlet obstruction. All attempts at endoscopic removal using a polypectomy snare, biopsy forceps and Dormia basket failed. We then injected Coca Cola directly into the bezoar mass, followed by irrigation with Coca Cola. Follow-up endoscopy was performed the next day, which revealed that the gastric bezoars had dissolved spontaneously.

  1. Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action

    International Nuclear Information System (INIS)

    Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

    2004-01-01

    The present study was undertaken to determine the vascular actions of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide (NO), in isolated canine cerebral arteries and to gain insight into its potential mechanisms of action. In the absence of any vasoactive agent, ONOO - (from 10 -7 to 10 -6 M) was able to reduce the basal tension. In prostaglandin F2α-precontracted canine basilar arterial rings, ONOO - elicited concentration-dependent relaxation at concentrations from 10 -8 to 10 -5 M. The effective concentrations producing approximately 50% maximal relaxation (EC 50 ) to ONOO - were 4.06 x 10 -6 and 4.12 x 10 -6 M in intact and denuded rings, respectively (P > 0.05). No significant differences in relaxation responses were found in ring preparations with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on rings precontracted by high KCL (P > 0.05). Addition of low concentrations of calyculin A (50 nM) was able to abolish the ONOO - -induced relaxation. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized canine cerebral rings in a concentration-related manner. Lastly, a variety of pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, etc., did not influence the relaxant effects of ONOO - on the rings. Our new results suggest that ONOO - -triggered relaxation, on canine cerebral arteries, is mediated by elevation of cyclic guanosine monophosphate (cGMP) levels, membrane hyperpolarization via K+ channel activation, activation of myosin light chain phosphatase activity, and interference with

  2. Selective binding of sucralfate to endoscopic mucosal resection-induced gastric ulcer: evaluation of aluminium adherence.

    Science.gov (United States)

    Itoh, T; Kusaka, K; Kawaura, K; Kashimura, K; Yamakawa, J; Takahashi, T; Kanda, T

    2004-01-01

    We evaluated the effect of sucralfate in patients with early gastric cancer in endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with or without ranitidine and were examined endoscopically after 1 week, 2 weeks and 3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated and normal mucosa were measured at various time-points. Good ulcer healing was observed in all patients. Significantly higher concentrations of aluminium were found in ulcerated tissue compared with normal mucosa. This selective binding of sucralfate was even found 12 h after drug administration and was confirmed in acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was observed up to 12 h after the administration of sucralfate alone. These results suggest that sucralfate with or without ranitidine may contribute to the healing of EMR-induced ulcers by selectively binding to lesions.

  3. Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Tadashi Nakamura

    2014-01-01

    Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

  4. Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats.

    Science.gov (United States)

    Werawatganon, Duangporn; Rakananurak, Narisorn; Sallapant, Sasipim; Prueksapanich, Piyapan; Somanawat, Kanjana; Klaikeaw, Naruemon; Rerknimitr, Rungsun

    2014-12-28

    To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy. Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 6) was given distilled water (DW) orally. Group 2 (IMN, n = 6) was given oral IMN (150 mg/kg) dissolved in 5% sodium bicarbonate (NaHCO3 (-)) at time 0 and 4 h. Group 3 (Aloe vera-treated, n = 6) was given oral Aloe vera (150 mg/kg) dissolved in DW and IMN at time 0 and 4 h. Eight hours later, the stomach was removed to determine gastric malondialdehyde (MDA), the number of interleukin (IL)-18 positive stained cells (%) by immunohistochemistry, and for histopathological examination. Then, the serum was collected to determine tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 by sandwich enzyme linked immunosorbent assay method. In the IMN group, serum TNF-α, CINC-1 and gastric MDA were significantly increased when compared to the control group (27.78 ± 1.52 pg/mL vs 85.07 ± 49.11 pg/mL, P = 0.009; 104.55 ± 45.80 pg/mL vs 1054.70 ± 20.38 pg/mL, and 1.74 ± 0.21 nmol/mg vs 9.36 ± 1.07 nmol/mg protein, P = 0.000, respectively). The mean level of TNF-α, CINC-1 and gastric MDA in the Aloe vera-treated group were improved as compared with the IMN group (85.07 ± 49.11 pg/mL vs 35.19 ± 1.61 pg/mL, P = 0.021; 1054.70 ± 20.38 pg/mL vs 813.56 ± 239.04 pg/mL, P = 0.025; and 9.36 ± 1.07 nmol/mg vs 2.67 ± 0.64 nmol/mg protein, P = 0.000, respectively). The number of IL-18 positive stained cells (%) in the gastric epithelial cells of the IMN group was significantly higher than the control group (5.01% ± 3.73% vs 30.67% ± 2.03%, P = 0.000, respectively). In contrast, Aloe vera treatment decreased the number of IL-18 positive stained cells (%) significantly when compared with the IMN group (30.67% ± 2.03% vs 13.21% ± 1.10%, P = 0.000, respectively). Most rats in the IMN group developed moderate to severe gastric inflammation

  5. Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

    Directory of Open Access Journals (Sweden)

    Dongjun Luo

    2016-01-01

    Full Text Available Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA. We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.

  6. [Effect of Capsicum annum L (pucunucho, ají mono) in gastric ulcer experimentally induced in rats].

    Science.gov (United States)

    Delgado Montero, Rocío; Flores Cortez, Daisy; Villalobos Pacheco, Eduardo

    2015-01-01

    To examine the effects of the Capsicum annum L lyophilized fruit extract in experimentally-induced gastric ulcer in rats. We used the model of indomethacin gastric ulcer-induced and the gastric ulcer model induced by pylorus ligation in rats. The rats were divided in five treatment groups as follow: G1: Distilled water 1 ml/Kg; G2: Ranitidine 50 mg/kg, G3: Capsicum 10mg/kg, G4: Capsicum 100 mg/kg, G5: Capsicum 1000 mg/kg. The results of the first model showed an ulcer inhibition of 60,4% and 66,7% using the doses of Capsicum at 10 mg/kg and 100 mg/kg, respectively. The results of the second model showed that neither the pH nor the volume of the gastric content were modified by the administered extract (p >0.05); however, by using the doses of Capsicum at 100 mg/kg and 1000 mg/kg, there was clearly an ulcer inhibition of 75.59% and 81.63% respectively, which were even greater than the inhibition obtained by ranitidine (75.51%). Therefore, in this experiment we demonstrated that the Capsicum annum L lyophilized fruit extract has a gastroprotective effect in experimentally-induced gastric ulcer in rats.

  7. Effect of esophageal distention on basal and stimulated gastric acid secretion in rats

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    Mohammad Kazem Gharib Nasery

    2007-02-01

    Full Text Available Background: It is well established that the esophageal distention leads to gastric relaxation, partly by vago-vagal reflex but till now, the effect of esophageal distention on gastric acid secretion has not been investigated. The aim of this study was to investigate the effect of esophageal distention (ED on basal and stimulated gastric acid secretion. Methods: Adult male Wistar rats (200-240g were deprived of food but not water for 24 hrs before the experiments. Under urethane anesthesia (1.2 g/kg, i.p., animals underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through duodenum for gastric distention and gastric washout and the esophagus was cannulated with a distensible balloon orally to distend esophagus (0.3 ml, 10 min. Gastric acid secretion was stimulated by gastric distention, carbachol (4 µg/kg, i.p. or histamine (5 mg/kg, s.c.. Effects of vagotomy, L-NAME (10 mg/kg, i.v., L-arginine (500 mg/kg, i.p. and hexamethonium were also investigated. Results: Esophageal distention reduces basal and gastric distention, carbachol and histamine stimulated acid secretion (P<0.05, P<0.0001, P<0.01 and P<0.02, respectively. Vagotomy reduced the inhibitory effect of the esophagus distention on gastric distention-induced acid secretion (P<0.05. Conclusion: These results indicate that vagus nerve involves in the inhibitory effect of the esophageal distention on the basal and stimulated gastric acid secretion. Nitric oxide (NO may also be involved.

  8. Relaxation model of radiation-induced conductivity in polymers

    Science.gov (United States)

    Zhutayeva, Yu. R.; Khatipov, S. A.

    1999-05-01

    The paper suggests a relaxation model of radiation-induced conductivity (RIC) in polymers. According to the model, the transfer of charges generated in the polymer volume by ionizing radiation takes place with the participation of molecular relaxation processes. The mechanism of electron transport consists in the transfer of the charge directly between traps when they draw close to one another due to the rotation of macromolecule segments. The numerical solutions of the corresponding kinetic equations for different distribution functions Q( τ) of the times of molecular relaxation and for different functions of the probability P( τ, τ') of charge transfer in the `overlapping' regions of the diffusion spheres of the segments are analyzed. The relaxation model provides an explanation of the non-Arrhenius behavior of the RIC temperature dependence, the power dependence of RIC on the dose rate with a power index in the interval 0.5-1.0, the appearance of maxima in the curves of the RIC temporal dependence and their irreversible character in the region of large dose rates (more than 1 Gy/s). The model can be used for interpreting polymer RIC in conditions of kinetic mobility of macromolecules.

  9. Relaxation dispersion in MRI induced by fictitious magnetic fields.

    Science.gov (United States)

    Liimatainen, Timo; Mangia, Silvia; Ling, Wen; Ellermann, Jutta; Sorce, Dennis J; Garwood, Michael; Michaeli, Shalom

    2011-04-01

    A new method entitled Relaxation Along a Fictitious Field (RAFF) was recently introduced for investigating relaxations in rotating frames of rank ≥ 2. RAFF generates a fictitious field (E) by applying frequency-swept pulses with sine and cosine amplitude and frequency modulation operating in a sub-adiabatic regime. In the present work, MRI contrast is created by varying the orientation of E, i.e. the angle ε between E and the z″ axis of the second rotating frame. When ε > 45°, the amplitude of the fictitious field E generated during RAFF is significantly larger than the RF field amplitude used for transmitting the sine/cosine pulses. Relaxation during RAFF was investigated using an invariant-trajectory approach and the Bloch-McConnell formalism. Dipole-dipole interactions between identical (like) spins and anisochronous exchange (e.g., exchange between spins with different chemical shifts) in the fast exchange regime were considered. Experimental verifications were performed in vivo in human and mouse brain. Theoretical and experimental results demonstrated that changes in ε induced a dispersion of the relaxation rate constants. The fastest relaxation was achieved at ε ≈ 56°, where the averaged contributions from transverse components during the pulse are maximal and the contribution from longitudinal components are minimal. RAFF relaxation dispersion was compared with the relaxation dispersion achieved with off-resonance spin lock T(₁ρ) experiments. As compared with the off-resonance spin lock T(₁ρ) method, a slower rotating frame relaxation rate was observed with RAFF, which under certain experimental conditions is desirable. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Arginase attenuates inhibitory nonadrenergic noncholinergic nerve-induced nitric oxide generation and airway smooth muscle relaxation

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    Meurs Herman

    2005-03-01

    Full Text Available Abstract Background Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO production, presumably by competition with epithelial constitutive NO synthase for the common substrate, L-arginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS-mediated relaxation induced by inhibitory nonadrenergic noncholinergic (iNANC nerve stimulation. Methods Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 μM atropine and 3 μM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM, while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 μM. Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine. Results EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P Conclusion The results indicate that endogenous arginase activity attenuates iNANC nerve-mediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.

  11. Vinorelbine induced perforation of a metastatic gastric lesion.

    Science.gov (United States)

    Mullally, W J; O'Súilleabháin, C B; Brady, C; O'Reilly, S

    2017-08-01

    Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted

  12. Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Sagradas, Joana; Costa, Gustavo; Figueirinha, Artur; Castel-Branco, Maria Margarida; Silvério Cabrita, António Manuel; Figueiredo, Isabel Vitória; Batista, Maria Teresa

    2015-09-15

    Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide

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    Zhongjian Cheng

    2018-06-01

    Full Text Available Insufficient hydrogen sulfide (H2S has been implicated in Type 2 diabetic mellitus (T2DM and hyperhomocysteinemia (HHcy-related cardiovascular complications. We investigated the role of H2S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA of db/db mice fed a high methionine (HM diet. HM diet (8 weeks induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively, and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF-induced endothelium-dependent relaxation to acetylcholine (ACh, determined by the presence of eNOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME and prostacyclin (PGI2 inhibitor indomethacin (INDO, in SMA from db/db mice but not that from db/+ mice. A non-selective Ca2+-active potassium channel (KCa opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective KCa blocker TEA and intermediate-conductance KCa blocker (IKCa Tram-34, but not by small-conductance KCa (SKCa blocker Apamin. HHcy potentiated the reduction of free sulfide, H2S and cystathionine γ-lyase protein, which converts L-cysteine to H2S, in SMA of db/db mice. Importantly, a stable H2S donor DATS diminished the enhanced O2- production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IKCa tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by KCa blockers. Conclusions: Intermediate HHcy potentiated H2S reduction via CSE-downregulation in microvasculature of T2DM mice. H2S is justified as an EDHF. Insufficient H2S

  14. Duodenal Bulb Mucosa with Hypertrophic Gastric Oxyntic Heterotopia in Patients with Zollinger Ellison Syndrome

    Science.gov (United States)

    Kohan, Emil; Oh, David; Wang, Hank; Hazany, Salar; Ohning, Gordon; Pisegna, Joseph R.

    2009-01-01

    Objectives. Zollinger-Ellison Syndrome (ZES) results in hypersecretion of gastric acid (via gastrinoma) leading to peptic ulcers, diarrhea, and abdominal pain. We describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the proximal duodenal bulb in patients with ZES, which we hypothesize results in an increased incidence of postbulbar ulcers in patients with ZES (a mechanism previously unreported). We determined the incidence of the novel finding of duodenal gastric oxyntic hypertrophic heterotopia (GOH) in patients with ZES. Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was established by hypergastrinemia, gastric acid hypersecretion, and a positive secretin test or based on biopsy specimens (evaluated via tissue staining). Basal acid output (BAO) and baseline gastrin secretion were determined by established methods. Endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa were conducted in all patients every 3–6 months for an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria in 5 patients. Two of the patients had no evidence of GOH in the duodenal bulb. Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of 2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions. This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. The presence of hypertrophic and heterotopic gastric mucosa is proposed to result from increased gastrin levels and may contribute to the increased incidence of postbulbar ulcers in these patients. PMID:19587828

  15. Duodenal Bulb Mucosa with Hypertrophic Gastric Oxyntic Heterotopia in Patients with Zollinger Ellison Syndrome

    Directory of Open Access Journals (Sweden)

    Emil Kohan

    2009-01-01

    Full Text Available Objectives. Zollinger-Ellison Syndrome (ZES results in hypersecretion of gastric acid (via gastrinoma leading to peptic ulcers, diarrhea, and abdominal pain. We describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the proximal duodenal bulb in patients with ZES, which we hypothesize results in an increased incidence of postbulbar ulcers in patients with ZES (a mechanism previously unreported. We determined the incidence of the novel finding of duodenal gastric oxyntic hypertrophic heterotopia (GOH in patients with ZES. Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was established by hypergastrinemia, gastric acid hypersecretion, and a positive secretin test or based on biopsy specimens (evaluated via tissue staining. Basal acid output (BAO and baseline gastrin secretion were determined by established methods. Endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa were conducted in all patients every 3–6 months for an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria in 5 patients. Two of the patients had no evidence of GOH in the duodenal bulb. Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of 2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions. This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. The presence of hypertrophic and heterotopic gastric mucosa is proposed to result from increased gastrin levels and may contribute to the increased incidence of postbulbar ulcers in these patients.

  16. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    International Nuclear Information System (INIS)

    Nicolau, L.A.D.; Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D.; Aragão, K.S.; Barbosa, A.L.R.; Soares, P.M.G.; Souza, M.H.L.P.; Medeiros, J.V.R.

    2013-01-01

    Our objective was to investigate the protective effect of Lawesson's reagent, an H 2 S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm 2 ); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm 2 ); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K ATP ) channels

  17. Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers.

    Science.gov (United States)

    Yi, Ruokun; Wang, Rui; Sun, Peng; Zhao, Xin

    2015-07-01

    Dragon-pearl tea is a type of green tea commonly consumed in Southwest China. In the present study, the antioxidative and anti-gastric ulcer effects of Dragon-pearl tea crude polyphenols (DTCP) were determined in vitro and in vivo . Treatment with 25, 50 or 100 µg/ml DTCP resulted in notable antioxidant effects in vitro , which manifested as 2,2-diphenyl-1-picrylhydrazyl and OH radical-scavenging activity. Furthermore, using an in vivo mouse model, DTCP was shown to reduce the gastric ulcer area in the stomach, in which the 200 mg/kg DTCP dose exhibited the most marked effect, with a gastric ulcer index inhibitory rate of 72.63%. In addition, DTCP was demonstrated to improve stomach acidity conditions in vivo by increasing the pH and reducing the level of gastric juice, as compared with the reserpine-induced gastric ulcer control mice. Furthermore, DTCP altered the serum levels of a number of oxidation-related biomolecules, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), lipid peroxidation (LPO) and catalase (CAT), to subsequently exert an anti-gastric ulcer effect. Treatment with 50, 100 and 200 mg/kg DTCP increased the SOD, GSH-Px and CAT levels and reduced the MDA and LPO levels in the mouse model of gastric ulcers. These serum level alterations resulted in the modified serum levels of prostaglandin E2 (PGE2) and nitric oxide (NO), which are associated with gastric mucosal protection. A reverse transcription-quantitative polymerase chain reaction (RT-PCR) assay is a molecular biology experiment which could determine the changes of mRNA in tissues. Using the RT-PCR assay, DTCP was observed to increase the mRNA expression levels of certain genes associated with gastric ulcers: Epidermal growth factor, epidermal growth factor receptor, vascular endothelial growth factor and vascular endothelial growth factor receptor 1, while reducing gastrin expression levels. Therefore, the results indicated that DTCP induced a

  18. Ion beam induced stress formation and relaxation in germanium

    Energy Technology Data Exchange (ETDEWEB)

    Steinbach, T., E-mail: Tobias.Steinbach@uni-jena.de [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany); Reupert, A.; Schmidt, E.; Wesch, W. [Institut für Festkörperphysik, Friedrich-Schiller-Universität Jena, Max-Wien-Platz 1, D-07743 Jena (Germany)

    2013-07-15

    Ion irradiation of crystalline solids leads not only to defect formation and amorphization but also to mechanical stress. In the past, many investigations in various materials were performed focusing on the ion beam induced damage formation but only several experiments were done to investigate the ion beam induced stress evolution. Especially in microelectronic devices, mechanical stress leads to several unwanted effects like cracking and peeling of surface layers as well as changing physical properties and anomalous diffusion of dopants. To study the stress formation and relaxation process in semiconductors, crystalline and amorphous germanium samples were irradiated with 3 MeV iodine ions at different ion fluence rates. The irradiation induced stress evolution was measured in situ with a laser reflection technique as a function of ion fluence, whereas the damage formation was investigated by means of Rutherford backscattering spectrometry. The investigations show that mechanical stress builds up at low ion fluences as a direct consequence of ion beam induced point defect formation. However, further ion irradiation causes a stress relaxation which is attributed to the accumulation of point defects and therefore the creation of amorphous regions. A constant stress state is reached at high ion fluences if a homogeneous amorphous surface layer was formed and no further ion beam induced phase transition took place. Based on the results, we can conclude that the ion beam induced stress evolution seems to be mainly dominated by the creation and accumulation of irradiation induced structural modification.

  19. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata

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    Saheed Sabiu

    2015-01-01

    Full Text Available This study investigated the quantitative polyphenolic constituents and gastroprotective effects of aqueous leaf extracts of Spondias mombin and Ficus exasperata against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg body weight. Wistar rats were pretreated with esomeprazole (reference drug at a dose of 20 mg/kg body weight, S. mombin or F. exasperata at 100 and 200 mg/kg body weight once daily for 21 days prior to ulcer induction. At the end of the experiment, gastric secretions and antioxidant parameters were evaluated. We observed that the significantly increased (p < 0.05 ulcer index, gastric volume, malondialdehyde level and pepsin activity were effectively reduced following treatment with S. mombin and F. exasperata. The extracts also markedly attenuated the reduced activity of superoxide dismutase as well as pH and mucin content in the ulcerated rats. These findings are indicative of gastroprotective and antioxidative potentials of the extracts which is also evident in the degree of % inhibition against ulceration. The available data in this study suggest that the extracts of S. mombin and F. exasperata proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.

  20. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

    Science.gov (United States)

    Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

    2007-02-01

    Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

  1. Antioxidant effects of betaine against Indomethacin-induced gastric damage in rats

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    M Alirezaei

    2016-10-01

    Full Text Available Introduction: Betaine (trimethyl glycine is known as methyl group donor and antioxidant in previous reports. The aim of this study was to assess the antioxidant effects of betaine in Indomethacin-induced gastric damages. Methods: Thirty-two adult male Sprague–Dawley rats in an experimental study were divided into four equal groups as follow: Control, Indomethacin, Betaine-indomethacin and Ascorbic acid-indomethacin. Control and indomethacin groups received normal saline and betaine and ascorbic acid-pretreated rats were administrated betaine (1.5% of the total diet and ascorbic acid (50 mg/kg body weight for 15 consecutive days, respectively. After 24 h fasting, all of the groups received indomethacin (48 mg/kg body weight and control group received distilled water. Results: Indomethacin administration increased gastric ulcer occurrence (% in comparison with control group and betaine pretreatment significantly decreased ulcer occurrence (% when compared to the other groups (P=0.0017. Gastric wall glutathione peroxidase (GPx activity was significantly lower in indomethacin group in comparison with the other groups (P=0.0012 while, betaine and ascorbic acid pretreatment increased GPx activity in comparison with indomethacin group (P=0.0012. Catalase activity was significantly higher in betaine-pretreated rats in comparison with indomethacin and ascorbic acid-indomethacin groups (P=0.0015. Lipid peroxidation significantly decreased in betaine and ascorbic acid pretreated groups (P=0.0013. Conclusion: These results showed beneficial antioxidant effects of betaine against gastric damages induced by indomethacin in rats.

  2. Endogenous histamine and promethazine-induced gastric ulcers in the guinea pig

    Science.gov (United States)

    Djahanguiri, B.; Hemmati, M.

    1978-01-01

    Experiments performed with an inhibitor of diaminoxydase, aminoguanidine and an inhibitor of histidine decarboxylase, NSD 1055, showed that the frequency of gastric ulcers induced by promethazine was increased with the first inhibitor and decreased with the second. It is suggested that ulcers induced by promethazine in guinea pigs might be due to histamino-liberator effect of the antihistaminio compound.

  3. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

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    Ayşin Akıncı

    2017-02-01

    Full Text Available Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57 was higher than that of the control group (1.50±0.22 (p<0.05. Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05, the stress and stress + standard diet groups (p<0.05, and the stress and stress + LPZ groups (p<0.05. The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05. Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50 and superoxide dismutase (15.18±1.05 and catalase (16.68±2.29 activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system

  4. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

    Directory of Open Access Journals (Sweden)

    Hany H Arab

    Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

  5. Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

    2010-01-01

    Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

  6. Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

    2010-03-01

    Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

  7. Role of duodenal mucosal nerve endings in the acid-induced duodenogastric sensorimotor reflex: effect of benzocaine in healthy humans.

    Science.gov (United States)

    Vanuytsel, T; Karamanolis, G; Vos, R; Van Oudenhove, L; Farré, R; Tack, J

    2013-05-01

    Duodenal acid exposure induces a duodenogastric reflex resulting in gastric relaxation, inhibition of antral motility, and sensitization of the proximal stomach to distension. Duodenal hypersensitivity to acid has been identified as a potential pathogenic mechanism in functional dyspepsia. The nature and localization of the duodenal acid-sensitive receptors are still elusive. We hypothesize that acid directly activates superficial afferent nerve endings in the duodenal mucosa, triggering the duodenogastric reflex. In a double-blind, randomized, crossover study in 13 healthy volunteers, benzocaine, a local anesthetic, vs saline was perfused in the duodenum 15 min before duodenal acid perfusion. Gastric responses were monitored by a barostat. Stepwise isobaric gastric distensions were performed before and during acid perfusion. Symptoms were evaluated by visual analogue scales for six dyspeptic symptoms and an overall perception score. Benzocaine perfusion caused a relaxation of the stomach prior to duodenal acidification, indicating the existence of an excitatory duodenogastric tone. Pretreatment of the duodenum with benzocaine reduced the acid-induced gastric relaxation by 50% and abolished the inhibition of phasic motility of the proximal stomach. Finally, sensitization to distension was more pronounced in the benzocaine condition because of higher proximal gastric volumes. These findings support a model in which different neuronal subpopulations are responsible for the motor and sensory limb of the acid-sensitive duodenogastric reflex, making benzocaine an unsuitable drug to treat duodenal hypersensitivity to acid. These data provide more insight in the contribution of duodenal neuronal input to gastric physiology in the fasting state. © 2013 Blackwell Publishing Ltd.

  8. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

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    Liu Jun

    2004-07-01

    Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Methods Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53 and MKN-28 (mutant-type p53. RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. Results BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45, or in p53 mutant-type (MKN-28 gastric cancer cells. Conclusions The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

  9. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

    International Nuclear Information System (INIS)

    Tong, Qiang-Song; Zheng, Li-Duan; Wang, Liang; Liu, Jun; Qian, Wei

    2004-01-01

    BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G 0 /G 1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45), or in p53 mutant-type (MKN-28) gastric cancer cells. The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies

  10. Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Radulović, Niko S; Jovanović, Ivan; Ilić, Ivan R; Randjelović, Pavle J; Stojanović, Nikola M; Miltojević, Ana B

    2013-11-19

    Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol. The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done. The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia. Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management. © 2013.

  11. Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile

    Directory of Open Access Journals (Sweden)

    Konstantin V. Kudryavtsev

    2014-01-01

    Full Text Available This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

  12. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

    Science.gov (United States)

    Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

    2007-11-01

    Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

  13. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    Directory of Open Access Journals (Sweden)

    Philip A. Robinson

    2013-10-01

    Full Text Available Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.

  14. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Park, Won-Mee; Sakata, Ichiro

    2013-01-01

    The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro......, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi....../o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi...

  15. A novel vitamin E derivative (TMG) protects against gastric mucosal damage induced by ischemia and reperfusion in rats.

    Science.gov (United States)

    Ichikawa, Hiroshi; Yoshida, Norimasa; Takano, Hiroshisa; Ishikawa, Takeshi; Handa, Osamu; Takagi, Tomohisa; Naito, Yuji; Murase, Hironobu; Yoshikawa, Toshikazu

    2003-01-01

    The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemia-reperfusion (I/R) -induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-alpha and CINC-2beta in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.

  16. Gastric emptying in rats with acetaminophen-induced hepatitis

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    G. Hessel

    1998-09-01

    Full Text Available The objective of this work was to study the gastric emptying (GE of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each. Group I was fed a sucrose diet throughout the experiment (66 h while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each. Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg. Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml than in group IB (87 µg/ml. The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values. The correlation between gastric retention and AST levels was significant (P<0.05 for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.

  17. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nicolau, L.A.D. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D. [Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Aragão, K.S. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Barbosa, A.L.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Soares, P.M.G.; Souza, M.H.L.P. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Medeiros, J.V.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil)

    2013-08-16

    Our objective was to investigate the protective effect of Lawesson's reagent, an H{sub 2}S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm{sup 2}); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm{sup 2}); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K

  18. Relaxant effect of the ethanol extract of Helichrysum plicatum (Asteraceae) on isolated rat ileum contractions.

    Science.gov (United States)

    Bigovic, Dubravka; Brankovic, Suzana; Kitic, Dusanka; Radenkovic, Mirjana; Jankovic, Teodora; Savikin, Katarina; Zivanovic, Slavoljub

    2010-05-10

    Helichrysum plicatum (Turkish Helichrysum) has been used in folk medicine for the treatment of gastric and hepatic disorders. The aim of the present study was to examine the relaxant activity of an extract of H. plicatum flowers on isolated rat ileum. Segments of ileum of rats were suspended in an organ bath. Cumulative concentrations of H. plicatum ethanol extract induced a relaxant effect on spontaneous rat ileum contractions. H. plicatum extract caused a mean contractile response of 81.68 +/- 6.17% (at a dose of 0.01 mg/mL) and 30.08 +/- 9.07% (at a dose of 1 mg/mL). A similar effect was observed with papaverine (0.01-3 microg/mL). H. plicatum extract (0.01-1 mg/mL) relaxed high K+ (80 mM) precontractions, an effect similar to that caused by papaverine (0.01-3 microg/mL). The plant extract (0.03-0.3 mg/mL) also induced a significant depression of the cumulative concentration response curve for acetylcholine (5-1500 nM) (p Helichrysum plicatum flowers on the isolated rat intestine Extract of H. plicatum can inhibit the spontaneous ileum contractions and contractions induced by acetylcholine, histamine, barium and potassium ions.

  19. Electroacupuncture improves burn-induced impairment in gastric motility mediated via the vagal mechanism in rats.

    Science.gov (United States)

    Song, J; Yin, J; Sallam, H S; Bai, T; Chen, Y; Chen, J D Z

    2013-10-01

    Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. (i) Burn delayed GE (P Electroacupuncture improved GE 6 and 24 h post burn (P Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6. © 2013 John Wiley & Sons Ltd.

  20. Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

    Directory of Open Access Journals (Sweden)

    Katarzyna Magierowska

    Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

  1. Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.

    Science.gov (United States)

    Sabarwal, Akash; Agarwal, Rajesh; Singh, Rana P

    2017-02-01

    The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Mastication suppresses initial gastric emptying by modulating gastric activity.

    Science.gov (United States)

    Ohmure, H; Takada, H; Nagayama, K; Sakiyama, T; Tsubouchi, H; Miyawaki, S

    2012-03-01

    Because various mastication-related factors influence gastric activity, the functional relationship between mastication and gastric function has not been fully elucidated. To investigate the influence of mastication on gastric emptying and motility, we conducted a randomized trial to compare the effects of mastication on gastric emptying and gastric myoelectrical activity under conditions that excluded the influences of food comminution, taste, and olfaction. A (13)C-acetate breath test with electrogastrography and electrocardiography was performed in 14 healthy men who ingested a test meal with or without chewing gum. Autonomic nerve activity was evaluated by fluctuation analysis of heart rate. Gastric emptying was significantly delayed in the 'ingestion with mastication' group. Gastric myoelectrical activity was significantly suppressed during mastication and increased gradually in the post-mastication phase. A decrease in the high-frequency power of heart rate variability was observed coincidentally with gastric myoelectrical activity suppression. These findings suggest that initial gastric emptying is suppressed by mastication, and that the suppression is caused by mastication-induced inhibition of gastric activity (UMIN Clinical Trial Registration no. UMIN000005351).

  3. Gastro-protective effect of methanol extract of Vernonia amygdalina (del. leaf on aspirin-induced gastric ulcer in Wistar rats

    Directory of Open Access Journals (Sweden)

    Modinat A. Adefisayo

    Full Text Available This study investigated the protective effects of methanol extract of Vernonia amygdalina leaf (MEVA on aspirin induced gastric ulcer in rats. Thirty Wistar rats, 150–200 g were divided into six groups as follows: Group 1 (control rats received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer Control received 150 mg/kg/day of aspirin suspended in 3 mL of 1% carboxymethylcellulose in water orally for 3 consecutive days during which the rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100 mg/kg/day orally for 28 consecutive days and thereafter treated as group 2. Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively for 28 consecutive days and thereafter were treated with aspirin as group 2. All the animals were sacrifice at the end of the study to determine the gastric pH, gastric acidity, gastric ulcer score, haematological indices, superoxide dismutase (SOD activity, reduced glutathione (GSH and Lipid peroxidation (LPO levels. The result showed that aspirin significantly (p < 0.05 increased gastric ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH level as well as increased LPO level. It induced significant necrosis of the stomach tissue. Administration of MEVA significantly (p < 0.05 increased gastric pH, but decreased gastric acid secretion and reversed alteration of haematological parameters. It also significantly (p < 0.05 increased SOD activity, GSH level and decreased LPO level. The results suggest that Vernonia amygdalina possesses gastro-protective properties against aspirin-induced gastric ulcer. Keywords: Vernonia amygdalina, Aspirin, Gastric ulcer, Antioxidant, Rat

  4. The time-dependence of exchange-induced relaxation during modulated radio frequency pulses.

    Science.gov (United States)

    Sorce, Dennis J; Michaeli, Shalom; Garwood, Michael

    2006-03-01

    The problem of the relaxation of identical spins 1/2 induced by chemical exchange between spins with different chemical shifts in the presence of time-dependent RF irradiation (in the first rotating frame) is considered for the fast exchange regime. The solution for the time evolution under the chemical exchange Hamiltonian in the tilted doubly rotating frame (TDRF) is presented. Detailed derivation is specified to the case of a two-site chemical exchange system with complete randomization between jumps of the exchanging spins. The derived theory can be applied to describe the modulation of the chemical exchange relaxation rate constants when using a train of adiabatic pulses, such as the hyperbolic secant pulse. Theory presented is valid for quantification of the exchange-induced time-dependent rotating frame longitudinal T1rho,ex and transverse T2rho,ex relaxations in the fast chemical exchange regime.

  5. Hypotonic duodenography and secretin-CCK test in the diagnosis of pancreatic disease

    International Nuclear Information System (INIS)

    Lukes, P.J.; Rolny, P.; Nilson, A.E.; Gamklou, R.

    1981-01-01

    Sixty-five patients with possible pancreatic disease or long-standing upper abdominal symptoms were examined by means of the secretin-CCK test and hypotonic duodenography. Both examinations were performed after one duodenal intubation. In patients with pancreatitis functional abnomalities were revealed in 85 per cent while the duodenography was abnormal in 43 per cent. In patients with carcinoma, 77 per cent had abnormal exocrine pancreas function and 70 per cent had abnormalities demonstrated at duodenography. The value of the two examinations for assessment of patients with upper abdominal symptoms and pancreatic disease is discussed. (Auth.)

  6. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Stephen J Kentish

    Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

  7. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  8. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-07-21

    To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  9. Pathobiology of Helicobacter pylori-induced Gastric Cancer

    Science.gov (United States)

    Amieva, Manuel; Peek, Richard M.

    2015-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  10. Effect of Cissus quadrangularis on gastric mucosal defensive factors in experimentally induced gastric ulcer-a comparative study with sucralfate.

    Science.gov (United States)

    Jainu, Mallika; Devi, C S Shyamala

    2004-01-01

    Cissus quadrangularis is an indigenous plant commonly mentioned in Ayurveda for treatment of gastric ulcers. The ulcer-protective effect of a methanolic extract of C. quadrangularis (CQE) was comparable to that of the reference drug sucralfate. Further, gastric juice and mucosal studies showed that CQE at a dose of 500 mg/kg given for 10 days significantly increased the mucosal defensive factors like mucin secretion, mucosal cell proliferation, glycoproteins, and life span of cells. The present investigation suggests that CQE not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation. Thus, CQE has potential usefulness for treatment of peptic ulcer disease.

  11. Ethyl nitrite is produced in the human stomach from dietary nitrate and ethanol, releasing nitric oxide at physiological pH: potential impact on gastric motility.

    Science.gov (United States)

    Rocha, Bárbara S; Gago, Bruno; Barbosa, Rui M; Cavaleiro, Carlos; Laranjinha, João

    2015-05-01

    Nitric oxide ((∙)NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity. The aim of this study was to ascertain whether compounds with physiological relevance are produced in the stomach upon consumption of nitrate- and ethanol-rich foods. Human volunteers consumed a serving of lettuce (source of nitrate) and alcoholic beverages (source of ethanol). After 15 min, samples of the gastric headspace were collected and ethyl nitrite was identified by GC-MS. Wistar rats were used to study the impact of ethyl nitrite on gastric smooth muscle relaxation at physiological pH. Nitrogen oxides, produced from nitrite in the stomach, induce nitrosation of ethanol from alcoholic beverages in the human stomach yielding ethyl nitrite. Ethyl nitrite, a potent vasodilator, is produced in vivo upon the consumption of lettuce with either red wine or whisky. Moreover, at physiological pH, ethyl nitrite induces gastric smooth muscle relaxation through a cGMP-dependent pathway. Overall, these results suggest that ethyl nitrite is produced in the gastric lumen and releases (∙)NO at physiological pH, which ultimately may have an impact on gastric motility. Systemic effects may also be expected if ethyl nitrite diffuses through the gastric mucosa reaching blood vessels, therefore operating as a (∙)NO carrier throughout the body. These data pinpoint posttranslational modifications as an underappreciated mechanism for the production of novel molecules with physiological impact locally in the gut and highlight the notion that diet may fuel compounds with the potential to modulate gastrointestinal welfare. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

    Science.gov (United States)

    Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

    2016-02-01

    To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

  13. Fish genomes provide novel insights into the evolution of vertebrate secretin receptors and their ligand.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Trindade, Marlene; Power, Deborah M

    2014-12-01

    The secretin receptor (SCTR) is a member of Class 2 subfamily B1 GPCRs and part of the PAC1/VPAC receptor subfamily. This receptor has long been known in mammals but has only recently been identified in other vertebrates including teleosts, from which it was previously considered to be absent. The ligand for SCTR in mammals is secretin (SCT), an important gastrointestinal peptide, which in teleosts has not yet been isolated, or the gene identified. This study revises the evolutionary model previously proposed for the secretin-GPCRs in metazoan by analysing in detail the fishes, the most successful of the extant vertebrates. All the Actinopterygii genomes analysed and the Chondrichthyes and Sarcopterygii fish possess a SCTR gene that shares conserved sequence, structure and synteny with the tetrapod homologue. Phylogenetic clustering and gene environment comparisons revealed that fish and tetrapod SCTR shared a common origin and diverged early from the PAC1/VPAC subfamily group. In teleosts SCTR duplicated as a result of the fish specific whole genome duplication but in all the teleost genomes analysed, with the exception of tilapia (Oreochromis niloticus), one of the duplicates was lost. The function of SCTR in teleosts is unknown but quantitative PCR revealed that in both sea bass (Dicentrarchus labrax) and tilapia (Oreochromis mossambicus) transcript abundance is high in the gastrointestinal tract suggesting it may intervene in similar processes to those in mammals. In contrast, no gene encoding the ligand SCT was identified in the ray-finned fishes (Actinopterygii) although it was present in the coelacanth (lobe finned fish, Sarcopterygii) and in the elephant shark (holocephalian). The genes in linkage with SCT in tetrapods and coelacanth were also identified in ray-finned fishes supporting the idea that it was lost from their genome. At present SCTR remains an orphan receptor in ray-finned fishes and it will be of interest in the future to establish why SCT was

  14. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  15. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  16. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    International Nuclear Information System (INIS)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

    2011-01-01

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

  17. Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    Albaayit SFA

    2016-06-01

    Full Text Available Shaymaa Fadhel Abbas Albaayit,1,2 Yusuf Abba,3 Rasedee Abdullah,4 Noorlidah Abdullah1 1Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq; 3Department of Veterinary Pathology and Microbiology, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20, 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05 smaller ulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in

  18. Hypotensive effect and vascular relaxation in different arteries induced by the nitric oxide donor RuBPY.

    Science.gov (United States)

    Pereira, Amanda de Carvalho; Araújo, Alice Valença; Paulo, Michele; Andrade, Fernanda Aparecida de; Silva, Bruno Rodrigues; Vercesi, Juliana Aparecida; da Silva, Roberto Santana; Bendhack, Lusiane Maria

    2017-01-30

    NO donors are compounds that release NO that can be used when the endogenous NO bioavailability is impaired. The compound cis-[Ru(bpy) 2 (py)(NO 2 )](PF 6 ) (RuBPY) is a nitrite-ruthenium, since it has a NO 2 in its molecule. The aim of the present study was to evaluate the effect of RuBPY on arterial pressure, as well as on the vascular relaxation of different vascular arteries in renal hypertensive (2K-1C) and normotensive (2K) rats. We have evaluated the arterial pressure and heart rate changes as well as the RuBPY and SNP-induced relaxation (thoracic aorta, mesenteric resistance, coronary and basilar arteries). The administration of RuBPY in awake rats evoked a smaller but long lasting hypotensive effect when compared to SNP, with no increase in heart rate. The relaxation induced by RuBPY was similar between 2K-1C and 2K rats in thoracic aorta, mesenteric resistance and coronary arteries. However, the relaxation induced by RuBPY was smaller in basilar arteries from 2K-1C than in 2K. Taken together, our results show that RuBPY presents several advantages over SNP, since it does not induce hypotensive effect in normotensive animals, the hypotensive effect is slower, with no reflex tachycardia, and it is long lasting. In addition, RuBPY induces coronary artery relaxation (useful for angina) and presented only a small effect on basilar artery (may not induce headache). Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Secretin stimulates HCO3(-) and acetate efflux but not Na+/HCO3(-) uptake in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I; Christoffersen, B C

    2001-01-01

    to be important in HCO3(-) -transporting epithelia. pHi was measured with BCECF in freshly isolated intralobular ducts. A reduction in extracellular Na+ concentration or application of HOE 694 (1 microM) decreased pHi by 0.1 to 0.6 pH units, demonstrating Na+/H+ exchanger activity. A reduction in extracellular Cl......- concentration or addition of H2DIDS (10 microM) increased pHi by 0.1 to 0.5 pH units, demonstrating Cl-/ HCO(3)- (OH ) exchanger activity. In experimental acidosis, extracellular HCO3(-)/CO2 buffer did not increase the rate of pHi recovery, indicating that provision of HCO3(-) by the Na+/HCO3(-) cotransporter...... was not apparent. Most importantly, Na+/HCO3(-) cotransport was not stimulated by secretin (1 nM). In contrast, in experimental alkalosis the pHi recovery was increased in HCO3(-)/CO2 buffer, possibly due to Na+/HCO3(-) cotransport in the efflux mode. Secretin (1 nM) and carbachol (1 microM) stimulated HCO3...

  20. Remodeling of the residual gastric mucosa after roux-en-y gastric bypass or vertical sleeve gastrectomy in diet-induced obese rats.

    Directory of Open Access Journals (Sweden)

    Konstantinos Arapis

    Full Text Available Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB and vertical sleeve gastrectomy (VSG in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H+/K+-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.

  1. The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

    Science.gov (United States)

    Ma, Long; Liu, Jiangguang

    2014-12-02

    Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this

  2. TFF1 inhibits proliferation and induces apoptosis of gastric cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Yanli Ge

    2012-05-01

    Full Text Available Trefoil Factor Family (TFF plays an essential role in the intestinal epithelial restitution, but the relationship between TFF1 and gastric cancer (GC is still unclear. The present study aimed to determine the role of TFF1 in repairing gastric mucosa and in the pathogenesis of GC.The TFF1 expression in different gastric mucosas was measured with immunohistochemistry. Then, siRNA targeting TFF1 or plasmids expressing TFF1 gene were transfected into BGC823 cells, SGC7901 cells and GES-1 cells. The cell proliferation was detected with MTT assay and apoptosis and cell cycle measured by flow cytometry.From normal gastric mucosa to mucosa with dysplasia and to gastric cancer, the TFF1 expression had a decreasing trend. Down-regulation of TFF1 expression significantly reduced the apoptosis of three cell lines and markedly facilitated their proliferation but had no significant effect on cell cycle. Over-expression of TFF1 could promote apoptosis of three cell lines and inhibit proliferation but had no pronounced effect on cell cycle. TFF1 can inhibit proliferation and induce apoptosis of GC cells in vitro.

  3. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    Science.gov (United States)

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota

  4. Saffron Aqueous Extract Inhibits the Chemically-induced Gastric Cancer Progression in the Wistar Albino Rat

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    S. Zahra Bathaie

    2013-01-01

    Full Text Available Objective(s: Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L. aqueous extract (SAE on the 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG-induced gastric cancer in rat was investigated. Materials and Methods: MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum and stomach of rats. Results: Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca2+, tyrosine kinase activity and carcino-embryonic antigen were not significant. Conclusion: SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner.

  5. Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Leite, L.N. [Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Gonzaga, N.A. [Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tirapelli, D.P.C.; Tirapelli, L.F. [Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tirapelli, C.R. [Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-08-15

    The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F{sub 1α} (6-keto-PGF{sub 1α}; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM{sub 22-52}, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP{sub 8-37}, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with N{sup G}-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K{sup +} channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K{sup +} channels), and

  6. Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

    International Nuclear Information System (INIS)

    Leite, L.N.; Gonzaga, N.A.; Tirapelli, D.P.C.; Tirapelli, L.F.; Tirapelli, C.R.

    2014-01-01

    The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F 1α (6-keto-PGF 1α ; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM 22-52 , a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP 8-37 , a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with N G -nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K + channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K + channels), and apamin (Ca 2+ -activated

  7. Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.

    Science.gov (United States)

    da Silva, Luisa Mota; Burci, Ligia de Moura; Crestani, Sandra; de Souza, Priscila; da Silva, Rita de Cássia Melo Vilhena de Andrade Fonseca; Dartora, Nessana; de Souza, Lauro Mera; Cipriani, Thales Ricardo; da Silva-Santos, José Eduardo; André, Eunice; Werner, Maria Fernanda de Paula

    2018-04-01

    Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET. The effects of EET on H + , K + -ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed. The incubation with EET (1000 µg/ml) partially inhibited H + , K + -ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100-1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl 2 in Ca 2+ -free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca 2+ -free nutritive solution. Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H + , K + -ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.

  8. Solute induced relaxation in glassy polymers: Experimental measurements and nonequilibrium thermodynamic model

    International Nuclear Information System (INIS)

    Minelli, Matteo; Doghieri, Ferruccio

    2014-01-01

    Data for kinetics of mass uptake from vapor sorption experiments in thin glassy polymer samples are here interpreted in terms of relaxation times for volume dilation. To this result, both models from non-equilibrium thermodynamics and from mechanics of volume relaxation contribute. Different kind of sorption experiments have been considered in order to facilitate the direct comparison between kinetics of solute induced volume dilation and corresponding data from process driven by pressure or temperature jumps

  9. Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle.

    Science.gov (United States)

    Chino, Daisuke; Sone, Tomoyo; Yamazaki, Kumi; Tsuruoka, Yuri; Yamagishi, Risa; Shiina, Shunsuke; Obara, Keisuke; Yamaki, Fumiko; Higai, Koji; Tanaka, Yoshio

    2018-01-01

    Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10 -7 M). Atenolol (a selective β 1 -AR antagonist; 3 × 10 -7 -10 -6  M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA 2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β 2 -AR antagonist) at 10 -9 -10 -8  M, but was competitively antagonized by 10 -7 -3 × 10 -7  M, with a pA 2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10 -7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA 2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β 1 -AR and β 3 -AR.

  10. Anthraquinone G503 Induces Apoptosis in Gastric Cancer Cells through the Mitochondrial Pathway

    Science.gov (United States)

    Li, Shuai; Duan, Junting; Ye, Fang; Li, Hanxiang; She, Zhigang; Gao, Guoquan; Yang, Xia

    2014-01-01

    G503 is an anthraquinone compound isolated from the secondary metabolites of a mangrove endophytic fungus from the South China Sea. The present study elucidates the anti-tumor activity and the underlying mechanism of G503. Cell viability assay performed in nine cancer cell lines and two normal cell lines demonstrated that the gastric cancer cell line SGC7901 is the most G503-sensitive cancer cells. G503 induced SGC7901 cell death via apoptosis. G503 exposure activated caspases-3, -8 and -9. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK and caspase-9 inhibitor Z-LEHD-FMK, but not caspase-8 inbibitor Z-IETD-FMK, attenuated the effect of G503. These results suggested that the intrinsic mitochondrial apoptosis pathway, rather than the extrinsic pathway, was involved in G503-induced apoptosis. Furthermore, G503 increased the ratio of Bax to Bcl-2 in the mitochondria and decreased the ratio in the cytosol. G503 treatment resulted in mitochondrial depolarization, cytochrome c release and the subsequent cleavage of caspase -9 and -3. Moreover, it is reported that the endoplasmic reticulum apoptosis pathway may also be activated by G503 by inducing capase-4 cleavage. In consideration of the lower 50% inhibitory concentration for gastric cancer cells, G503 may serve as a promising candidate for gastric cancer chemotherapy. PMID:25268882

  11. Secretin Is an Ineffective Treatment for Pervasive Developmental Disabilities: A Review of 15 Double-Blind Randomized Controlled Trials

    Science.gov (United States)

    Sturmey, Peter

    2005-01-01

    In 1998, Horvath et al. [Horvath, K., Stefanatos, G., Sokolski, K. N., Wachtel, R., Nabors, L., & Tildon, J. T. (1998). Improved social and language skills after secretin administration in patients with autism spectrum disorders. "Journal of the Association of the Academy of Minority Physicians," 9, 9-15] reported an uncontrolled…

  12. Fetal responses to induced maternal relaxation during pregnancy.

    Science.gov (United States)

    DiPietro, Janet A; Costigan, Kathleen A; Nelson, Priscilla; Gurewitsch, Edith D; Laudenslager, Mark L

    2008-01-01

    Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-min guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed.

  13. Relaxation of soman-induced contracture of airway smooth muscle in vitro. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Filbert, M.G.; Moore, D.H.; Adler, M.

    1992-12-31

    A possible role for beta-adrenergic agonists in the management of bronchoconstriction resulting from exposure to anticholinesterase compounds was investigated in vitro in canine tracheal smooth muscle. Norepinephrine, salbutamol and isoproterenol produced partial relaxation of soman-induced contractures. However, the relaxation induced was not sustained; muscle tensions returned to pretreatment levels within minutes despite the continued presence of beta-agonists. Increasing cAMP levels with the non beta-agonist bronchodilators such as thoophylline, a phosphodiesterase inhibitor, or forskolin, a specific stimulator of adenylate cyclase, resulted in more complete and longer lasting relaxation, suggesting that beta-adrenoceptor desensitization may contribute to the failure by beta-agonists to produce sustained relaxation. Nerve agents, Soman, Toxicity, Airway smooth muscle, In vitro, Physiology, Effects.

  14. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.

    Science.gov (United States)

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-11-07

    Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with

  15. Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

    Science.gov (United States)

    Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

    1994-06-01

    In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

  16. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

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    Pedro M. G. Soares

    2011-03-01

    Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

  17. Secretin Modulates the Postnatal Development of Mouse Cerebellar Cortex Via PKA- and ERK-dependent Pathways

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-11-01

    Full Text Available Postnatal development of the cerebellum is critical for its intact function such as motor coordination and has been implicated in the pathogenesis of psychiatric disorders. We previously reported that deprivation of secretin (SCT from cerebellar Purkinje neurons impaired motor coordination and motor learning function, while leaving the potential role of SCT in cerebellar development to be determined. SCT and its receptor (SCTR were constitutively expressed in the postnatal cerebellum in a temporal and cell-specific manner. Using a SCT knockout mouse model, we provided direct evidence showing altered developmental patterns of Purkinje cells (PCs and granular cells (GCs. SCT deprivation reduced the PC density, impaired the PC dendritic formation, induced accelerated GC migration and potentiated cerebellar apoptosis. Furthermore, our results indicated the involvement of protein kinase A (PKA and extracellular signal regulated kinase (ERK signaling pathways in SCT-mediated protective effects against neuronal apoptosis. Results of this study illustrated a novel function of SCT in the postnatal development of cerebellum, emphasizing the necessary role of SCT in cerebellar-related functions.

  18. Characterization of P2Y receptors mediating ATP induced relaxation in guinea pig airway smooth muscle: involvement of prostaglandins and K+ channels.

    Science.gov (United States)

    Montaño, Luis M; Cruz-Valderrama, José E; Figueroa, Alejandra; Flores-Soto, Edgar; García-Hernández, Luz M; Carbajal, Verónica; Segura, Patricia; Méndez, Carmen; Díaz, Verónica; Barajas-López, Carlos

    2011-10-01

    In airway smooth muscle (ASM), adenosine 5'-triphosphate (ATP) induces a relaxation associated with prostaglandin production. We explored the role of K(+) currents (I (K)) in this relaxation. ATP relaxed the ASM, and this effect was abolished by indomethacin. Removal of airway epithelium slightly diminished the ATP-induced relaxation at lower concentration without modifying the responses to ATP at higher concentrations. ATPγS and UTP induced a concentration-dependent relaxation similar to ATP; α,β-methylene-ATP was inactive from 1 to 100 μM. Suramin or reactive blue 2 (RB2), P2Y receptor antagonists, did not modify the relaxation, but their combination significantly reduced this effect of ATP. The relaxation was also inhibited by N-ethylmaleimide (NEM; which uncouples G proteins). In myocytes, the ATP-induced I (K) increment was not modified by suramin or RB2 but the combination of both drugs abolished it. This increment in the I (K) was also completely nullified by NEM and SQ 22,536. 4-Amynopyridine or iberiotoxin diminished the ATP-induced I (K) increment, and the combination of both substances diminished ATP-induced relaxation. The presence of P2Y(2) and P2Y(4) receptors in smooth muscle was corroborated by Western blot and confocal images. In conclusion, ATP: (1) produces relaxation by inducing the production of bronchodilator prostaglandins in airway smooth muscle, most likely by acting on P2Y(4) and P2Y(2) receptors; (2) induces I (K) increment through activation of the delayed rectifier K(+) channels and the high-conductance Ca(2+)-dependent K(+) channels, therefore both channels are implicated in the ATP-induced relaxation; and (3) this I (K) increment is mediated by prostaglandin production which in turns increase cAMP signaling pathway.

  19. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as “Medang payung” by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its

  20. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its prominent

  1. Gou-teng (from Uncaria rhynchophylla Miquel)-induced endothelium-dependent and -independent relaxations in the isolated rat aorta.

    Science.gov (United States)

    Kuramochi, T; Chu, J; Suga, T

    1994-01-01

    Gou-teng is a drug used for treatment of hypertension in Chinese medicine. Its antihypertensive action has been previously confirmed in the spontaneously hypertensive rat (SHR). Here, its vasorelaxing effect and the mechanisms of actions were studied in vitro. Gou-teng extract (GTE) relaxed the norepinephrine (NE)-precontracted aortic ring preparations isolated from Wistar Kyoto rats (WKY) with and without intact endothelium; the latter was significantly less sensitive than the former. The GTE-induced endothelium-dependent relaxation was significantly inhibited by NG-monomethyl-L-arginine (NMMA) in a dose-dependent manner while indomethacin did not affect the relaxation. Atropine inhibited the acetylcholine (ACh)-induced endothelium-dependent relaxation but did not the GTE-induced one. Furthermore, once GTE was applied, the following NE-induced contraction was significantly reduced even after repeated washout. NMMA effectively reduced and rather reversed this residual effect of GTE. From these results, it is concluded that GTE relaxes the NE-precontracted rat aorta through endothelium-dependent and, to lesser extent, -independent mechanisms. The endothelium-dependent component would be mediated by EDRF/NO pathway in which the muscarinic cholinoceptors were not involved. Thus, GTE appears to be a potent and long-lasting vasodilator mainly through EDRF/NO release.

  2. Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury.

    Science.gov (United States)

    Li, Kang; Gesang, Luobu; Dan, Zeng; Gusang, Lamu; Dawa, Ciren; Nie, Yuqiang

    2015-01-01

    High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients. HAPC caused morphological changes and pathological damages of the gastric mucosa of GML patients. A total of 10304 differentially expressed genes (DEGs) were identified, including 4941 up-regulated and 5363 down-regulated DEGs in gastric mucosa of GML patients compared with healthy controls (fold change ≥2, Ppolycythemia while polycythemia raises the risk of GML. Therefore, the present findings reveal that HAPC-induced GML inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF. These results may offer the basic information for the treatment of HAPC-induced gastric lesion in the future.

  3. Shuidouchi (Fermented Soybean Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury

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    Huayi Suo

    2015-11-01

    Full Text Available Shuidouchi (Natto is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein, and GVFS (glass vessel fermented Shuidouchi had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL and pH of gastric juice (3.1 of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL, gastrin (Gas level and increase somatostatin (SS, vasoactive intestinal peptide (VIP level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD, nitric oxide (NO and malonaldehyde (MDA contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

  4. Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.

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    José M Alvarez-Suarez

    Full Text Available 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

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

    Science.gov (United States)

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    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

  6. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

    OpenAIRE

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-01-01

    AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.

  7. CUSTOM RELAXATION INDUCED IMPURITY PHOTOCONDUCTIVITY IN THE UNITED AII BVI and AIII BV

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    L. B. Atlukhanova

    2016-01-01

    Full Text Available Two types of non-standard relaxation induced impurity photoconductivity (IIP observed in photoconductors CdS, ZnSe, GaAs and others, depending on the kinetic characteristics of the traps are described. In one case, at the stage of post flashing monotonic decay which is typical for relaxation associated with slow traps (the ratio of the speed of the electron capture to the recombination rate (R << 1, the photo response is experiencing vibrations of low frequency (f =0.03-0.3Hz. Relaxation of the second type characterized by rapid photoelectric traps (R >> 1: measurement alternating signal (f > 20 Hz relaxation curves take the form of curves usual impurity photoconductivity. Electronic processes responsible for relaxation of non-standard IIP are analyzed. For example, fast-centers, which include the characteristic AIIBVI donor Agi0, for the first time in semiconductors experimentally, investigated the dependence of the cross section of electron capture by traps energy released during localization.

  8. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

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    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  9. Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

    Science.gov (United States)

    Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

    2017-10-01

    Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

  10. Automatic gallbladder segmentation using combined 2D and 3D shape features to perform volumetric analysis in native and secretin-enhanced MRCP sequences.

    Science.gov (United States)

    Gloger, Oliver; Bülow, Robin; Tönnies, Klaus; Völzke, Henry

    2017-11-24

    We aimed to develop the first fully automated 3D gallbladder segmentation approach to perform volumetric analysis in volume data of magnetic resonance (MR) cholangiopancreatography (MRCP) sequences. Volumetric gallbladder analysis is performed for non-contrast-enhanced and secretin-enhanced MRCP sequences. Native and secretin-enhanced MRCP volume data were produced with a 1.5-T MR system. Images of coronal maximum intensity projections (MIP) are used to automatically compute 2D characteristic shape features of the gallbladder in the MIP images. A gallbladder shape space is generated to derive 3D gallbladder shape features, which are then combined with 2D gallbladder shape features in a support vector machine approach to detect gallbladder regions in MRCP volume data. A region-based level set approach is used for fine segmentation. Volumetric analysis is performed for both sequences to calculate gallbladder volume differences between both sequences. The approach presented achieves segmentation results with mean Dice coefficients of 0.917 in non-contrast-enhanced sequences and 0.904 in secretin-enhanced sequences. This is the first approach developed to detect and segment gallbladders in MR-based volume data automatically in both sequences. It can be used to perform gallbladder volume determination in epidemiological studies and to detect abnormal gallbladder volumes or shapes. The positive volume differences between both sequences may indicate the quantity of the pancreatobiliary reflux.

  11. Abnormal gastrointestinal endocrine cells in patients with diabetes type 1: relationship to gastric emptying and myoelectrical activity.

    Science.gov (United States)

    El-Salhy, M; Sitohy, B

    2001-11-01

    Gastrointestinal symptoms in patients with diabetes are believed to be caused by gastrointestinal dysmotility and secretion/absorption disturbances, and the gut endocrine cells play an important part in regulating these two functions. Studies on animal models of human diabetes type I revealed abnormality in these cells, but it is unknown whether abnormality also occurs in patients with diabetes. Eleven patients with long duration of diabetes type I and organ complications, as well as gastrointestinal symptoms, were studied. Endocrine cells in different segments of the gastrointestinal tract were detected by immunocytochemistry and quantified by computerized image analysis. Gastric emptying was measured by scintigraphy and gastric myoelectric activity was determined by electrogastrography. An abnormal density of gastrointestinal endocrine cells was found in patients with diabetes. This abnormality occurred in all segments of the upper and lower gastrointestinal tract investigated, and included most of the endocrine cell types. The patients showed delayed gastric emptying, which correlated closely with the acute glucose level, but did not correlate with HbA1c. Gastric emptying also correlated closely with the density of duodenal serotonin and secretin cells. The patients exhibited bradygastrias and tachygastrias. These dysrhythmias, however, did not differ significantly from controls. The endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. The abnormality in density of the gastrointestinal endocrine cells may contribute to the development of gastrointestinal dysmotility and the symptoms encountered in patients with diabetes.

  12. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation

  13. Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats

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    Nurhidayah Ab. Rahim

    2014-01-01

    Full Text Available Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg orally, positive control was administered with 20 mg/kg omeprazole (reference drug and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg.

  14. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

  15. Lactobacillus fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects

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    Huayi Suo

    2016-03-01

    Full Text Available The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin, SP (substance P, ET (endothelin levels of LF-Suo treated mice were lower, and SS (somatostatin, VIP (vasoactive intestinal peptide levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6, IL-12 (interleukin 12, TNF-α (tumor necrosis factor-α and IFN-γ (interferon-γ serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase, GSH-Px (glutathione peroxidase, NO (nitric oxide and activities of LF-Suo treated mice were increased and MDA (malondialdehyde activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor, EGFR (epidermal growth factor receptor, VEGF (vascular endothelial growth factor, Fit-1 (fms-like tyrosine kinase-1, IκB-α (inhibitor kappaB-α, nNOS (neuronal nitric oxide synthase, eNOS (endothelial nitric oxide synthase, Mn-SOD, Cu/Zn-SOD, CAT (catalase mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB, and iNOS (inducible nitric oxide synthase expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 109 CFU/kg b.w. of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 109 CFU/kg b.w. of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as

  16. Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo.

    Science.gov (United States)

    Zeng, Qiang; Ko, Chun-Hay; Siu, Wing-Sum; Li, Long-Fei; Han, Xiao-Qiang; Yang, Liu; Bik-San Lau, Clara; Hu, Jiang-Miao; Leung, Ping-Chung

    2017-08-17

    Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury. For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by H 2 O 2 . Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury. H 2 O 2 treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of H 2 O 2 on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by H 2 O 2 for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited H 2 O 2 -mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa. The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis

  17. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

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    Sena Lee

    2014-04-01

    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  18. Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

    Science.gov (United States)

    Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

    2005-01-01

    AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced

  19. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.

    Science.gov (United States)

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

  20. Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects.

    Science.gov (United States)

    Huang, Zhihui; Zhang, Nina; Xu, Feng; Yin, Jieyun; Dai, Ning; Chen, Jiande D Z

    2016-03-01

    Impaired gastric accommodation is recognized as one of major pathophysiologies in functional dyspepsia and gastroparesis. Electroacupuncture has been shown to improve gastric accommodation in laboratory settings. It is, however, unknown whether it exerts similar ameliorating effect in humans and whether needleless transcutaneous electroacupuncture (TEA) is also effective in improving gastric accommodation. The aim was to investigate the effects of TEA on gastric accommodation, gastric slow waves, and dyspeptic related symptoms. Thirteen healthy volunteers were studied in four randomized sessions: control, cold nutrient liquid, cold nutrient liquid + sham-TEA, and cold nutrient liquid + TEA. The subjects were requested to drink Ensure until reaching maximum satiety. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to assess the gastric and autonomic functions respectively. 1) Gastric accommodation was reduced with the cold drink in comparison with the warm drink (P = 0.023). TEA improved the impaired gastric accommodation from 539.2 ± 133.8 ml to 731.0 ± 185.7 ml (P = 0.005). 2) The percentage of normal gastric slow waves in six subjects was significantly decreased in the cold session (P = 0.002) and improved in the TEA session (P = 0.009 vs sham; P  0.05). TEA improves impaired gastric accommodation and slow waves induced by cold drink and the effect does not seem to be mediated via the vagal mechanisms. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. Effect of crude methanol leaf extract of Combretum racemosum on histamine-stimulated gastric secretion in rats

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    Chukwugozie Nwachukwu Okwuosa

    2017-02-01

    Full Text Available Objective: To investigate the effect of crude methanolic extract of Combretum racemosum (C. racemosum leaves on histamine-stimulated gastric secretion in rats. Methods: Phytochemical and acute toxicity tests were performed. Anti-secretory activity of C. racemosum extract was investigated in pyloric ligated rats administered histamine. Gastric juice was collected from all the animals and the volume, titratable acidity, pH and mucus content were measured. The effect of C. racemosum extract on calcium chloride induced contractions of the guinea-pig ileum suspended in high potassium, calcium-deficient depolarizing solution was investigated. The H2 receptor antagonistic potency was also evaluated using the isolated non-gravid rat uterus. Results: Phytochemistry revealed the presence of abundant amounts of saponins and moderate amounts of glycosides, terpenoids, proteins, reducing sugar, resins, alkaloids, flavonoids and carbohydrates. The oral LD50 of the extract was greater than 8 000 mg/kg body weight in mice. Pretreatment of pyloric ligated rats with C. racemosum prior to histamine administration significantly reduced (P < 0.001 the volume of gastric juice and titratable acidity, and significantly increased (P < 0.001 gastric pH and gastric mucus when compared to the negative control. Both doses of C. racemosum protected rats significantly (P < 0.001 from histamine-induced ulceration. C. racemosum potently inhibited contractions evoked by calcium chloride in a dose-dependent and reversible manner with an IC50 of 1 132 µg/mL. It also antagonized the relaxant effect of histamine on the isolated rat uterus in a manner comparable to cimetidine. Conclusions: The leaves of C. racemosum possess gastric anti-secretory and anti-ulcer effects and justify its use in traditional medicine in South-East Nigeria for the treatment of peptic ulcer disease.

  2. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

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    Yun Wu

    2016-01-01

    Full Text Available Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592, dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271, current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669 were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

  3. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

    Science.gov (United States)

    Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

    2016-03-15

    Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

    International Nuclear Information System (INIS)

    Wei, Min; Gu, Qinlong; Wang, Zhiwei; Yao, Hongliang; Yang, Zhongyin; Zhang, Qing; Liu, Bingya; Yu, Yingyan; Su, Liping; Zhu, Zhenggang

    2011-01-01

    Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer. Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA. HMBA increased p27Kip1 expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3β inhibition. The results presented herein suggest that GSK-3β functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial

  5. Activity of Brucea javanica oil emulsion against gastric ulcers in rodents

    Directory of Open Access Journals (Sweden)

    Qian Li

    2018-05-01

    Full Text Available The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion (BJOE in animals. Gastroprotective potential of BJOE was studied on absolute ethanol, aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid (GAA and pyloric ligation (PL-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly (P < 0.05 reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant (P < 0.05 suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PL-induced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future. Keywords: Gastric ulcer, Brucea javanica oil emulsion, Gastric mucosa, Ulcer scores, Glacial acetic acid, Pepsin activity

  6. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

    Science.gov (United States)

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy. PMID:27073325

  7. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  8. Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

    Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and healthy controls (HC) METHODS: Eighty-two patients with CP and 22 HC were enrolled in the study. Morphological imaging parameters included pancreatic main duct diameter, gland volume, fat signal fraction and apparent diffusion coefficient (ADC) values. Functional secretin-stimulated MRI (s-MRI) parameters included pancreatic secretion (bowel fluid volume) and changes in pancreatic ADC value before and after secretin stimulation. Patients were classified according to the modified Cambridge and M-ANNHEIM classification system and fecal elastase was collected. All imaging parameters differentiated CP patients from HC; however, correlations between morphological and functional parameters in CP were weak. Patients with alcoholic and non-alcoholic etiology had comparable s-MRI findings. Fecal elastase was positively correlated to pancreatic gland volume (r = 0.68, P = 0.0016) and negatively correlated to Cambridge classification (r = -0.35, P pancreatic gland volume was significantly decreased in the severe stages of CP (P = 0.001). S-MRI provides detailed information about pancreatic morphology and function and represents a promising non-invasive imaging method to characterize pancreatic pathophysiology and may enable monitoring of disease progression in patients with CP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  9. Secretin-stimulating MRCP in patients with pancreatobiliary maljunction and occult pancreatobiliary reflux: direct demonstration of pancreatobiliary reflux

    Energy Technology Data Exchange (ETDEWEB)

    Motosugi, Utaroh; Ichikawa, Tomoaki; Araki, Tsutomu [University of Yamanashi, Department of Radiology, Chuo-shi, Yamanashi (Japan); Kitahara, Fumiaki; Sato, Tadashi [University of Yamanashi, First Department of Internal Medicine, Chuo-shi, Yamanashi (Japan); Itakura, Jun; Fujii, Hideki [University of Yamanashi, First Department of Surgery, Chuo-shi, Yamanashi (Japan)

    2007-09-15

    We propose the hypothesis that the enlargement of the common bile duct (CBD) or gallbladder (GB) that is occasionally demonstrated on magnetic resonance cholangiopancreatography (MRCP) after secretin stimulation is caused by pancreatobiliary reflux. Recently, occult pancreatobiliary reflux (OPR) has been demonstrated in patients without morphological pancreatobiliary maljunction (MPBM). The aim of this study was to evaluate the efficacy of secretin-stimulating MRCP (SMRCP) in the diagnosis of pancreatobiliary reflux. The study included 14 patients with MPBM and 32 patients with a normal pancreatobiliary junction. OPR was evaluated by bile collection and diagnosed in seven of the 32 patients. All the patients underwent SMRCP; the related findings were considered positive when enlargement of the CBD or GB was observed. Positive findings on SMRCP were observed in all MPBM patients. In the patients with normal pancreatobiliary junction, there was significant difference between the mean amylase levels in the patients with positive and negative SMRCP findings (mean, 4,755.7 and 29.7 IU/l). The sensitivity and specificity of SMRCP for diagnosing OPR was 85.7% and 68.0%, respectively. SMRCP provides a non invasive method for excluding PBR and can identify patients who could benefit from bile duct sampling to diagnose OPR. (orig.)

  10. Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia

    Energy Technology Data Exchange (ETDEWEB)

    Donati, Francescamaria, E-mail: fra.donati@katamail.co [2nd Department of Radiology, Pisa University-Hospital, Via Paradisa 2, I-56124 Pisa (Italy); Boraschi, Piero; Gigoni, Roberto; Salemi, Simonetta [2nd Department of Radiology, Pisa University-Hospital, Via Paradisa 2, I-56124 Pisa (Italy); Faggioni, Lorenzo; Bertucci, Cristina; Cecchi, Claudia; Bartolozzi, Carlo [Diagnostic and Interventional Radiology, University of Pisa, Via Rome 67, I-56126 Pisa (Italy); Falaschi, Fabio [2nd Department of Radiology, Pisa University-Hospital, Via Paradisa 2, I-56124 Pisa (Italy)

    2010-08-15

    Purpose: To assess the diagnostic value of secretin-stimulated MRCP (SS-MRCP) compared with conventional MRCP in asymptomatic patients with mild elevations of pancreatic enzymes. Materials and methods: Eighty asymptomatic patients with pancreatic hyperenzymemia underwent MR imaging at 1.5 T-device (Signa EXCITE, GE Healthcare). After the acquisition of axial T1w,T2w sequences, and conventional MRCP, SS-MRCP was performed using a single-slice coronal breath-hold, thick-slab, SSFSE T2w sequence, repeated every 30 s up to 15 min following intravenous injection of secretin (Secrelux, Sanochemia). Results: On the basis of the standards of reference, our final diagnoses were: negative findings (n = 23), pancreas divisum (n = 22), mild chronic pancreatitis (n = 14), inflammatory ampullary stenosis (n = 3), juxtapapillary duodenal diverticulum (n = 1), small cystic lesions (<1 cm) (n = 22; 5/22 cases associated with pancreas divisum). The image quality of SS-MRCP was significantly higher than that of conventional MRCP (p < 0.0001). Standards of reference did not differ significantly from of SS-MRCP findings (p = 0.5), while was statistically different from those of conventional MRCP (p < 0.0001). A significant difference was found between conventional MRCP and SS-MRCP findings (p < 0.0001). Conclusion: In asymptomatic patients with non-specific pancreatic hyperenzymemia SS-MRCP may represent the best non-invasive diagnostic technique, since it gives morphological and functional information.

  11. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  12. Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

    International Nuclear Information System (INIS)

    Onodera, Akira; Kawai, Yuichi; Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio

    2013-01-01

    Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

  13. Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Akira, E-mail: onodera@pharm.kobegakuin.ac.jp [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kawai, Yuichi [Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2013-06-14

    Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

  14. Magneto-dependent stress relaxation of magnetorheological gels

    KAUST Repository

    Xu, Yangguang; Liu, Taixiang; Liao, G J; Lubineau, Gilles

    2017-01-01

    The stress relaxation behaviors of magnetorheological (MR) gels under stepwise shear loading are systematically investigated. The particle-enhanced effect, the magneto-induced effect, and the temperature-enhanced effect on the stress relaxation of MR gels are discussed. For further analysis of the magneto-induced stress relaxation mechanism in MR gels, a phenomenological model is established to describe the stress relaxation behavior of the matrix and the magnetic particle chains. All characteristic parameters introduced in the model, i.e. relaxation time, instantaneous modulus, and stable modulus, have well-defined physical meanings and are fitted based on the experimental results. The influence of each parameter on the macroscopic response is discussed and it is found that the relaxation stress induced by the magneto-mechanical coupling effect plays an important role in the stress relaxation process of MR gels.

  15. Magneto-dependent stress relaxation of magnetorheological gels

    KAUST Repository

    Xu, Yangguang

    2017-09-01

    The stress relaxation behaviors of magnetorheological (MR) gels under stepwise shear loading are systematically investigated. The particle-enhanced effect, the magneto-induced effect, and the temperature-enhanced effect on the stress relaxation of MR gels are discussed. For further analysis of the magneto-induced stress relaxation mechanism in MR gels, a phenomenological model is established to describe the stress relaxation behavior of the matrix and the magnetic particle chains. All characteristic parameters introduced in the model, i.e. relaxation time, instantaneous modulus, and stable modulus, have well-defined physical meanings and are fitted based on the experimental results. The influence of each parameter on the macroscopic response is discussed and it is found that the relaxation stress induced by the magneto-mechanical coupling effect plays an important role in the stress relaxation process of MR gels.

  16. The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats.

    Science.gov (United States)

    Boyacioglu, Murat; Kum, Cavit; Sekkin, Selim; Yalinkilinc, Hande Sultan; Avci, Hamdi; Epikmen, Erkmen Tugrul; Karademir, Umit

    2016-04-01

    Lycopene, the main antioxidant compound present in tomatoes, has high singlet oxygen- and peroxyl radicals-quenching ability, resulting in protection against oxidative damage in aerobic cell. Indomethacin is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in gastric tissue. The aim of this study was to investigate the protective effects of lycopene on an indomethacin-induced gastric ulcer model. A total of 42 adult male Wistar rats were divided into six groups of seven animals as follows: control, indomethacin, lansoprazole, lycopene 10 mg/kg, lycopene 50 mg/kg and lycopene 100 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of lycopene were administered by oral gavage. The efficacy of lycopene was compared with lansoprazole. DNA damage of lymphocytes was measured by comet assay. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. This tissue was also taken for pathological investigations. The TUNEL method was used to detect apoptotic cells in paraffin sections. The results showed that 100 mg/kg lycopene administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. This same dose of lycopene also significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Apoptosis rates in the stomachs of the rats correlated with the biochemical and histopathological findings. These results indicated that lycopene might have a protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Bcl-w, a Radio-resistant Protein, Promotes the Gastric Cancer Cell Migration by inducing the phosphorylation of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Bae, In Hwa; Yoon, Sung Hwan; Um, Hong Duck

    2008-01-01

    Gastric cancer is one of the leading malignancies in many countries and lethal for the high incidence of recurrence even after drastic surgical resection. Because local invasion and subsequent metastasis contributes to the failure of anticancer treatments of gastric cancer, a better understanding of the mechanisms involved in tumor invasiveness within the stomach seems to be essential for the control of this disease. Bcl-w is a prosurvival member of the Bcl-2 protein family, and thus protects cells from γ-irradiation. Recent reports suggest that Bcl-w can be upregulated in gastric cancer cells in a manner associated with the infiltrative (diffuse) types of the tumor. An analysis of Bcl-w function consistently revealed that Bcl-w can also promote the migratory and invasive potentials of gastric cancer cells. While it was shown that Bcl-w increases the invasiveness of cancer cells by sequentially inducing PI3K, Akt, SP1, and MMP-2, cellular components involved in Bcl-w-induced cell migration remain to be determined. This was the reason why we undertook the present study, which shows that FAK is a critical mediator of the cell migration induced by Bcl-w

  18. Altered expression of hypoxia-inducible factor-1α (HIF-1α and its regulatory genes in gastric cancer tissues.

    Directory of Open Access Journals (Sweden)

    Jihan Wang

    Full Text Available Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α, the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED was pursued to identify HIF-1α ↔ NFκB1 → BRCA1 → STAT3 ← STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3 were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1α in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1α-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.

  19. Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

    Science.gov (United States)

    Yang, Tao-Tao; Cao, Na; Zhang, Hai-Hui; Wei, Jian-Bo; Song, Xiao-Xia; Yi, Dong-Min; Chao, Shuai-Heng; Zhang, Li-Da; Kong, Ling-Fei; Han, Shuang-Yin; Yang, Yu-Xiu; Ding, Song-Ze

    2018-04-15

    Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased

  20. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  1. Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Gonzalo Carrasco

    2013-01-01

    Full Text Available Chronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266.

  2. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

    International Nuclear Information System (INIS)

    Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng

    2011-01-01

    β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer

  3. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

    Directory of Open Access Journals (Sweden)

    Bryony N Parsons

    2017-11-01

    Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

  4. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

    Science.gov (United States)

    Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

    2017-01-01

    Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

  5. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy

  6. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy. PMID:22646534

  7. Prevention of experimentally-induced gastric ulcers in rats by an ethanolic extract of "Parsley" Petroselinum crispum.

    Science.gov (United States)

    Al-Howiriny, Tawfeq; Al-Sohaibani, Mohammed; El-Tahir, Kamal; Rafatullah, Syed

    2003-01-01

    An ethanolic extract of Parsley, Petroselinum crispum (Mill.) Nym.ex A.W. Hill (Umbelliferae), was tested for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, indomethacin and cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) in rats. The extract in doses of 1 and 2 g/kg body weight had a significant antiulcerogenic activity on the models used. Besides, ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl contents were replenished by pretreatment with Parsley extract. Acute toxicity tests showed a large margin of safety for the extract. The phytochemical screening of Parsley leaves revealed the presence of tannins, flavonoids, sterols and/or triterpenes.

  8. On the relation between quasi-static and dynamic stress induced reversible structural relaxation of amorphous alloys

    International Nuclear Information System (INIS)

    Krueger, P.; Stucky, T.; Boewe, M.; Neuhaeuser, H.

    1993-01-01

    Quasi-static stress relaxation and dynamic internal friction measurements of stress induced reversible structural relaxation were performed on the amorphous alloy Fe 40 Ni 40 B 20 . The kinetics can be well described by a stretched exponential Kohlrausch-Williams-Watts quasi-static relaxation. The thermally activated part of the internal friction shows an Arrhenius temperature behaviour for a fixed vibration frequency and an inverse power frequency behaviour for a fixed temperature. The activation energies calculated from the Arrhenius equation and from the frequency shift method are significantly different. In order to explain this discrepancy the relation between the quasi-static and the dynamic descriptions of the reversible relaxation is reexamined. In particular it is shown that these two activation energies are connected by the Kohlrausch exponent of the quasi-static relaxation. (orig.)

  9. Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells.

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

    2012-01-27

    We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

  10. Comparison of the efficacy of 4- and 8-week lansoprazole treatment for ESD-induced gastric ulcers: a randomized, prospective, controlled study.

    Science.gov (United States)

    Park, Ji Hoon; Baek, Eun Kyung; Choi, Chang Hwan; Lee, Kyung Hun; Kim, Beom Jin; Kim, Jeong Wook; Kim, Jae Gyu; Chang, Sae Kyung

    2014-01-01

    Although endoscopic submucosal dissection (ESD) is widely used to treat gastric neoplasms, there is no consensus for the optimal treatment for ESD-induced ulcers. We compared efficacy between 4 and 8 weeks of lansoprazole treatment for iatrogenic gastric ulcers that developed after ESD. Eighty-four patients who were diagnosed with gastric adenoma or early gastric cancer were enrolled and randomly assigned to treatment with lansoprazole (30 mg/day) for 4 or 8 weeks. Eight weeks after ESD, we conducted follow-up endoscopy to compare ulcer stage and ulcer reduction ratio (dividing the ulcer dimension at 8 weeks by the initial ulcer dimension) between the two groups. From the 84 patients, 69 patients were included in the final analysis, with 34 in the 4-week group and 35 in the 8-week group. Eight weeks after ESD, there were no significant difference observed between the two groups in terms of the ulcer stage (68 % in the scar stage in the 4-week group vs. 69 % in the 8-week group, P = 0.93) or the ulcer reduction ratio (0.0081 ± 0.015 in the 4-week group vs. 0.0037 ± 0.008 in the 8-week group, P = 0.15). Also, in the subgroup analysis among the patients with large ulcers (>30 mm), those parameters were not different. For ESD-induced gastric ulcers, treatment with lansoprazole for 4 weeks was as effective as treatment for 8 weeks. Considering cost-effectiveness, proton pump inhibitor therapy for 4 weeks may be sufficient for ESD-induced gastric ulcers.

  11. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

    Directory of Open Access Journals (Sweden)

    Opeyemi J. Olatunji

    2015-12-01

    Full Text Available The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH, superoxide dismutase (SOD, malondialdehyde (MDA, myeloperoxidase (MPO activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

  12. Allium Cepa Ameliorates Ethanol-Induced Gastric Injury in Rats Via ...

    African Journals Online (AJOL)

    ACER

    (SOD) and Catalase (CAT) activities) were carried out in plasma and gastric tissue. ... glandular destruction in the gastric mucosa and infiltration of inflammatory ... Gastric injury is one of major diseases affecting ..... inflammatory bowel disease.

  13. Endoscopic appearance of irradiated gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    De Sagher, L I; Van den Heule, B; Van Houtte, P; Engelholm, L; Balikdjan, D; Bleiberg, H

    1979-09-01

    Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds.

  14. Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

    Directory of Open Access Journals (Sweden)

    Olga Bloch

    2015-01-01

    Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

  15. Pseudo-variables method to calculate HMA relaxation modulus through low-temperature induced stress and strain

    International Nuclear Information System (INIS)

    Canestrari, Francesco; Stimilli, Arianna; Bahia, Hussain U.; Virgili, Amedeo

    2015-01-01

    Highlights: • Proposal of a new method to analyze low-temperature cracking of bituminous mixtures. • Reliability of the relaxation modulus master curve modeling through Prony series. • Suitability of the pseudo-variables approach for a close form solution. - Abstract: Thermal cracking is a critical failure mode for asphalt pavements. Relaxation modulus is the major viscoelastic property that controls the development of thermally induced tensile stresses. Therefore, accurate determination of the relaxation modulus is fundamental for designing long lasting pavements. This paper proposes a reliable analytical solution for constructing the relaxation modulus master curve by measuring stress and strain thermally induced in asphalt mixtures. The solution, based on Boltzmann’s Superposition Principle and pseudo-variables concepts, accounts for time and temperature dependency of bituminous materials modulus, avoiding complex integral transformations. The applicability of the solution is demonstrated by testing a reference mixture using the Asphalt Thermal Cracking Analyzer (ATCA) device. By applying thermal loadings on restrained and unrestrained asphalt beams, ATCA allows the determination of several parameters, but is still unable to provide reliable estimations of relaxation properties. Without them the measurements from ATCA cannot be used in modeling of pavement behavior. Thus, the proposed solution successfully integrates ATCA experimental data. The same methodology can be applied to all test methods that concurrently measure stress and strain. The statistical parameters used to evaluate the goodness of fit show optimum correlation between theoretical and experimental results, demonstrating the accuracy of this mathematical approach

  16. Gradient-induced longitudinal relaxation of hyperpolarized noble gases in the fringe fields of superconducting magnets used for magnetic resonance.

    Science.gov (United States)

    Zheng, Wangzhi; Cleveland, Zackary I; Möller, Harald E; Driehuys, Bastiaan

    2011-02-01

    When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of (3)He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum (3)He relaxation rate of 3.83×10(-3) s(-1) (T(1)=4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T(1) would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T(1) of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient-induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Contact induced spin relaxation in graphene spin valves with Al2O3 and MgO tunnel barriers

    Directory of Open Access Journals (Sweden)

    Walid Amamou

    2016-03-01

    Full Text Available We investigate spin relaxation in graphene by systematically comparing the roles of spin absorption, other contact-induced effects (e.g., fringe fields, and bulk spin relaxation for graphene spin valves with MgO barriers, Al2O3 barriers, and transparent contacts. We obtain effective spin lifetimes by fitting the Hanle spin precession data with two models that include or exclude the effect of spin absorption. Results indicate that additional contact-induced spin relaxation other than spin absorption dominates the contact effect. For tunneling contacts, we find reasonable agreement between the two models with median discrepancy of ∼20% for MgO and ∼10% for Al2O3.

  18. Vascular relaxation induced by C-type natriuretic peptide involves the ca2+/NO-synthase/NO pathway.

    Directory of Open Access Journals (Sweden)

    Fernanda A Andrade

    Full Text Available AIMS: C-type natriuretic peptide (CNP and nitric oxide (NO are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3 contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. MAIN METHODS: Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. KEY FINDINGS: CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. SIGNIFICANCE: These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.

  19. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  20. Aerobic metabolism on muscle contraction in porcine gastric smooth muscle.

    Science.gov (United States)

    Kanda, Hidenori; Kaneda, Takeharu; Nagai, Yuta; Urakawa, Norimoto; Shimizu, Kazumasa

    2018-05-18

    Exposure to chronic hypoxic conditions causes various gastric diseases, including gastric ulcers. It has been suggested that gastric smooth muscle contraction is associated with aerobic metabolism. However, there are no reports on the association between gastric smooth muscle contraction and aerobic metabolism, and we have investigated this association in the present study. High K + - and carbachol (CCh)-induced muscle contractions involved increasing O 2 consumption. Aeration with N 2 (hypoxia) and NaCN significantly decreased high K + - and CCh-induced muscle contraction and O 2 consumption. In addition, hypoxia and NaCN significantly decreased creatine phosphate (PCr) contents in the presence of high K + . Moreover, decrease in CCh-induced contraction and O 2 consumption was greater than that of high K + . Our results suggest that hypoxia and NaCN inhibit high K + - and CCh-induced contractions in gastric fundus smooth muscles by decreasing O 2 consumption and intracellular PCr content. However, the inhibition of CCh-induced muscle contraction was greater than that of high K + -induced muscle contraction.

  1. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

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

  2. Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

    Science.gov (United States)

    Cousin, Fabien J.; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    Background Gastric cancer is one of the most common cancers in the world. The “economically developed countries” life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. Methodology/Principal Findings A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. Conclusions/Significance Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments. PMID:22442660

  3. Effects of Relaxing Music on Mental Fatigue Induced by a Continuous Performance Task: Behavioral and ERPs Evidence.

    Science.gov (United States)

    Guo, Wei; Ren, Jie; Wang, Biye; Zhu, Qin

    2015-01-01

    The purpose of this study was to investigate whether listening to relaxing music would help reduce mental fatigue and to maintain performance after a continuous performance task. The experiment involved two fatigue evaluation phases carried out before and after a fatigue inducing phase. A 1-hour AX-continuous performance test was used to induce mental fatigue in the fatigue-inducing phase, and participants' subjective evaluation on the mental fatigue, as well as their neurobehavioral performance in a Go/NoGo task, were measured before and after the fatigue-inducing phase. A total of 36 undergraduate students (18-22 years) participated in the study and were randomly assigned to the music group and control group. The music group performed the fatigue-inducing task while listening to relaxing music, and the control group performed the same task without any music. Our results revealed that after the fatigue-inducing phase, (a) the music group demonstrated significantly less mental fatigue than control group, (b) reaction time significantly increased for the control group but not for the music group, (c) larger Go-P3 and NoGo-P3 amplitudes were observed in the music group, although larger NoGo-N2 amplitudes were detected for both groups. These results combined to suggest that listening to relaxing music alleviated the mental fatigue associated with performing an enduring cognitive-motor task.

  4. Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

    Science.gov (United States)

    Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

    2017-07-01

    Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

  5. Inducing Assertive Behavior in Chronic Schizophrenics: A Comparison of Socioenvironmental Desensitization, and Relaxation Therapies

    Science.gov (United States)

    Weinman, Bernard; And Others

    1972-01-01

    It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)

  6. Lipolytic actions of secretin in mouse adipocytes[S

    Science.gov (United States)

    Sekar, Revathi; Chow, Billy K. C.

    2014-01-01

    Secretin (Sct), a classical gut hormone, is now known to play pleiotropic functions in the body including osmoregulation, digestion, and feeding control. As Sct has long been implicated to regulate metabolism, in this report, we have investigated a potential lipolytic action of Sct. In our preliminary studies, both Sct levels in circulation and Sct receptor (SctR) transcripts in adipose tissue were upregulated during fasting, suggesting a potential physiological relevance of Sct in regulating lipolysis. Using SctR knockout and Sct knockout mice as controls, we show that Sct is able to stimulate lipolysis in vitro in isolated adipocytes dose- and time-dependently, as well as acute lipolysis in vivo. H-89, a protein kinase A (PKA) inhibitor, was found to attenuate lipolytic effects of 1 μM Sct in vitro, while a significant increase in PKA activity upon Sct injection was observed in the adipose tissue in vivo. Sct was also found to stimulate phosphorylation at 660ser of hormone sensitive lipase (HSL) and to bring about the translocation of HSL from cytosol to the lipid droplet. In summary, our data demonstrate for the first time the in vivo and in vitro lipolytic effects of Sct, and that this function is mediated by PKA and HSL. PMID:24273196

  7. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  8. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  9. Increase of transient lower esophageal sphincter relaxation associated with cascade stomach

    Science.gov (United States)

    Kawada, Akiyo; Kusano, Motoyasu; Hosaka, Hiroko; Kuribayashi, Shiko; Shimoyama, Yasuyuki; Kawamura, Osamu; Akiyama, Junichi; Yamada, Masanobu; Akuzawa, Masako

    2017-01-01

    We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0–60 min), late period (60–120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying. PMID:28584403

  10. Control of magnetic relaxation by electric-field-induced ferroelectric phase transition and inhomogeneous domain switching

    Energy Technology Data Exchange (ETDEWEB)

    Nan, Tianxiang; Emori, Satoru; Wang, Xinjun; Hu, Zhongqiang; Xie, Li; Gao, Yuan; Lin, Hwaider; Sun, Nian, E-mail: n.sun@neu.edu [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts 02115 (United States); Peng, Bin; Liu, Ming, E-mail: mingliu@mail.xjtu.edu.cn [Electronic Materials Research Laboratory, Xi' an Jiaotong University, Xi' an 710049 (China); Jiao, Jie; Luo, Haosu [Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); Budil, David [Department of Chemistry, Northeastern University, Boston, Massachusetts 02115 (United States); Jones, John G.; Howe, Brandon M.; Brown, Gail J. [Materials and Manufacturing Directorate, Air Force Research Laboratory, Wright-Patterson AFB, Ohio 45433 (United States)

    2016-01-04

    Electric-field modulation of magnetism in strain-mediated multiferroic heterostructures is considered a promising scheme for enabling memory and magnetic microwave devices with ultralow power consumption. However, it is not well understood how electric-field-induced strain influences magnetic relaxation, an important physical process for device applications. Here, we investigate resonant magnetization dynamics in ferromagnet/ferroelectric multiferroic heterostructures, FeGaB/PMN-PT and NiFe/PMN-PT, in two distinct strain states provided by electric-field-induced ferroelectric phase transition. The strain not only modifies magnetic anisotropy but also magnetic relaxation. In FeGaB/PMN-PT, we observe a nearly two-fold change in intrinsic Gilbert damping by electric field, which is attributed to strain-induced tuning of spin-orbit coupling. By contrast, a small but measurable change in extrinsic linewidth broadening is attributed to inhomogeneous ferroelastic domain switching during the phase transition of the PMN-PT substrate.

  11. The gastric accommodation response to meal intake determines the occurrence of transient lower esophageal sphincter relaxations and reflux events in patients with gastro-esophageal reflux disease.

    Science.gov (United States)

    Pauwels, A; Altan, E; Tack, J

    2014-04-01

    Gastro-esophageal reflux (GER), the retrograde flow of gastric contents into the esophagus is a physiologic phenomenon, which can evoke symptoms and/or lesions in the esophagus (=gastro-esophageal reflux disease or GERD). Proton pump inhibitors (PPIs) reduce gastric acidity; however, as they are unable to control transient lower esophageal sphincter relaxations (TLESRs), the main mechanism for reflux in GERD, they do not abolish reflux. TLESRs occur predominantly in the postprandial period, and they are believed to be triggered by gastric distention. Gastric accommodation (GA) is the physiologic response to gastric distention and serves to prevent a rise in gastric wall tension during food intake. We aimed to study the relationship between GA and TLESRs, as they both are triggered by gastric distention. We studied 12 GERD patients (average age 37 years [range 18-62], 7m/5f) and nine healthy volunteers (average age 27 years [range 22-36], 2m/7f) using high resolution manometry-impedance measurement before and after a mixed meal challenge. We determined the number of TLESRs (with or without reflux) and measured pre- and postprandial IGP. The change in IGP between the pre- and postprandial period (ΔIGP) is used as surrogate for GA. We also measured LES pressure before and after the meal and calculated the change (ΔLESp). There were no statistical differences between pre- and postprandial IGP in GERD and healthy volunteers and similarly, there was no significant difference between pre- and postprandial LES pressures in GERD patients and healthy volunteers. The number of TLESRs (with or without reflux) was similar in GERD and healthy volunteers. More importantly, we did observe a negative correlation between ΔIGP and the number of TLESRs, irrespective of whether they were associated with reflux or not, in the GERD patients (without reflux r = -0.67, p = 0.017; with reflux r = -0.81, p = 0.0014). The same observations were found in healthy volunteers, where ΔIGP and

  12. Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

    Science.gov (United States)

    Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

    2011-07-01

    The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

  13. Testing of 99mTc labelled sucralfate in induced gastric and duodenal ulcers

    International Nuclear Information System (INIS)

    Pallagi, Katalin; Janoki, Gyoezoe

    1988-01-01

    The conditions of in vitro labelling of sucralfate available in medical practice were established according to literature data including some modifications. Labelling efficiency proved to be 98.1%. The radiopharmaceutical is stable over 6 hours in vitro. 99m Tc-sucralfate accumulates in experimentally induced gastric and duodenal ulcers thus tracing the site of the ulcerous lesion. (author) 14 refs.; 3 tabs

  14. Psychophysiological correlates of relaxation induced by standard autogenic training.

    Science.gov (United States)

    Mishima, N; Kubota, S; Nagata, S

    1999-01-01

    The present study aimed to determine the psychophysiological changes induced in subjects by standard autogenic training (AT). Physiological measurements were taken under strict experimental conditions. Thirty-one healthy students were divided randomly into two groups: the AT group and the control group. In the first session, the physiological variables were measured for all students before and after all were asked to relax in their own way. The AT group were then taught AT for 3 months, after which time the measurements were repeated. In the second session, the AT group practised the standard AT exercise, while the control group repeated their own form of simple relaxation. Electrocardiogram, plethysmogram (PTG) and blood pressure (BP) were measured while the students carried out a breathing rate of 15 cycles/min. The R-R intervals and BP were analysed by an autoregressive model for spectral analysis, and the data were compared by repeated-measures ANOVA. The AT group had a significant increase in the mean R-R interval and a significant decrease in the baseline deflection of the PTG in the second session. There were no significant changes in sympathetic activity except for the change in the PTG, although low frequency amplitude of systolic BP decreased slightly. AT was found to induce significant changes that were independent of respiration in healthy students, although paced breathing might have operated as a mental stress. The increase in mean R-R interval and the decrease in baseline deflection of the PTG were the most robust correlates of AT.

  15. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

    Directory of Open Access Journals (Sweden)

    António M. Santos

    2015-01-01

    Full Text Available Helicobacter pylori (H. pylori infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT and quantitative real-time polymerase chain reaction (PCR. Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

  16. Uridine Adenosine Tetraphosphate-Induced Coronary Relaxation Is Blunted in Swine With Pressure Overload: A Role for Vasoconstrictor Prostanoids.

    Science.gov (United States)

    Zhou, Zhichao; Lankhuizen, Inge M; van Beusekom, Heleen M; Cheng, Caroline; Duncker, Dirk J; Merkus, Daphne

    2018-01-01

    Plasma levels of the vasoactive substance uridine adenosine tetraphosphate (Up 4 A) are elevated in hypertensive patients and Up 4 A-induced vascular contraction is exacerbated in various arteries isolated from hypertensive animals, suggesting a potential role of Up 4 A in development of hypertension. We previously demonstrated that Up 4 A produced potent and partially endothelium-dependent relaxation in the porcine coronary microvasculature. Since pressure-overload is accompanied by structural abnormalities in the coronary microvasculature as well as by endothelial dysfunction, we hypothesized that pressure-overload blunts the coronary vasodilator response to Up 4 A, and that the involvement of purinergic receptors and endothelium-derived factors is altered. The effects of Up 4 A were investigated using wire-myography in isolated coronary small arteries from Sham-operated swine and swine with prolonged (8 weeks) pressure overload of the left ventricle induced by aortic banding (AoB). Expression of purinergic receptors and endothelium-derived factors was assessed in isolated coronary small arteries using real-time PCR. Up 4 A (10 -9 to 10 -5 M) failed to produce contraction in isolated coronary small arteries from either Sham or AoB swine, but produced relaxation in preconstricted arteries, which was significantly blunted in AoB compared to Sham. Blockade of purinergic P1, and P2 receptors attenuated Up 4 A-induced coronary relaxation more, while the effect of P2X 1 -blockade was similar and the effects of A 2A - and P2Y 1 -blockade were reduced in AoB as compared to Sham. mRNA expression of neither A1, A2, A3, nor P2X 1 , P2X 7 , P2Y 1 , P2Y 2 , nor P2Y 6 -receptors was altered in AoB as compared to Sham, while P2Y 12 expression was higher in AoB. eNOS inhibition attenuated Up 4 A-induced coronary relaxation in both Sham and AoB. Additional blockade of cyclooxygenase enhanced Up 4 A-induced coronary relaxation in AoB but not Sham swine, suggesting the involvement

  17. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

    OpenAIRE

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-01-01

    Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL)....

  18. Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

    Science.gov (United States)

    Li, Long-Gang; Xu, Hui-Mian

    2005-01-01

    AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma. METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression was detected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOS expression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P<0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high AIs (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low AIs (0.79%; 47.14%) (P = 0.001). COX’s multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69). CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival. PMID:15849807

  19. Radioimmunoassay for serotin - methodology, basal and stimulated hormone concentration in plasma of rats, dogs, rabbits and humans

    International Nuclear Information System (INIS)

    Wittmann, J.K.

    1983-01-01

    A radioimmunoassay for measurement of secretin in the plasma of experimental animals and man has been developed by means of the so-called stripping procedure (pre-treatment of plasma with Quso). The detection limit is about 7 pg/ml at a final dilution of 1:630 000 and an equilibrium constant of 2.1x10 -11 L/M. By means of this system plasma secretin in the species examined can be measured reliably. The coefficients of variation are (percent): The within assay precision (intra-assay) 12, the between assay precision (inter-assay) 23. The median of basal venous plasma secretin are (pg/ml) dog 16, rabbit 0, rat (aorta) 0, rat (porta) 31, man 0. From these studies it is concluded that a) as a consequence of unspecific interference of plasma particles with the secretin RIA-system only a previous removal of these interfering factors leads to reliable test results; should this pre-requisite be neglected falsely too high results are to be expected; b) plasma secretin rises if there is either hydrochloric acid present in the duodenum or if gastric together with food particles reaches the duodenum; c) at least in the dog there may be different molecular species of secretin circulating in the peripherical plasma, however the biological role of these is unknown at present. (orig./TRV) [de

  20. Intraoperative Gastric Suctioning and Postoperative Nausea, Retching, and Vomiting.

    Science.gov (United States)

    1984-07-01

    of Anesthesiologists CTZ -chemoreceptor trigger zone IV - intravenous kg. - kilogram LES - lower esophageal sphincter Mzg. -milligram ml. -milliliter...the stomach or duedenum * . -= provides the strongest stimulus for vomiting" (Guyton, 1981). Sensory impulses originating in the upper gastro ...duodenum may cause nausea and can result in intestinal contraction during gastric relax- ... , ation allowing reflux of intestinal contents into the

  1. Recombinant outer membrane secretin PilQ(406-770) as a vaccine candidate for serogroup B Neisseria meningitidis.

    Science.gov (United States)

    Haghi, Fakhri; Peerayeh, Shahin Najar; Siadat, Seyed Davar; Zeighami, Habib

    2012-02-21

    Secretin PilQ is an antigenically conserved outer membrane protein which is present on most meningococci. This protein naturally expressed at high levels and is essential for meningococcal pilus expression at the cell surface. A 1095 bp fragment of C-terminal of secretin pilQ from serogroup B Neisseria meningitidis was cloned into prokaryotic expression vector pET-28a. Recombinant protein was overexpressed with IPTG and affinity-purified by Ni-NTA agarose. BALB/c mice were immunized subcutaneously with purified rPilQ(406-770) mixed with Freund's adjuvant. Serum antibody responses to serogroups A and B N. meningitidis whole cells or purified rPilQ(406-770) and functional activity of antibodies were determined by ELISA and SBA, respectively. The output of rPilQ(406-770) was approximately 50% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with PilQ(406-770) mixed with Freund's adjuvant in comparison with control groups. Antisera produced against rPilQ(406-770) demonstrated strong surface reactivity to serogroups A and B N. meningitidis tested by whole-cell ELISA. Surface reactivity to serogroup B N. meningitidis was higher than serogroup A. The sera from PilQ(406-770) immunized animals were strongly bactericidal against serogroups A and B. These results suggest that rPilQ(406-770) is a potential vaccine candidate for serogroup B N. meningitidis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. A biochemical study on the gastroprotective effect of andrographolide in rats induced with gastric ulcer.

    Science.gov (United States)

    Saranya, P; Geetha, A; Selvamathy, S M K Narmadha

    2011-09-01

    The major objective of the study was to evaluate the gastroprotective property of andrographolide, a chief component of the leaves of Andrographis paniculata in terms of the ulcer preventive effect in rats. An acute toxicity test was conducted with different concentrations of andrographolide to determine the LD(50) value. The dose responsive study was conducted in rats pretreated with andrographolide (1, 3 and 5 mg/kg) for a period of 30 days, prior to ulcer induction by administering ethanol, aspirin or by pyloric ligation. The ulcer protective efficacy was tested by determining the ulcer score, pH, pepsin, titrable acidity, gastric mucin, lipid peroxides, reduced glutathione, and enzymatic antioxidants superoxide dismutase, catalase and glutathione peroxidase in gastric tissue. The activities of H(+)-K(+) ATPase and myeloperoxidase were also determined in gastric tissue. The LD(50) value was found to be 48 mg/kg b. wt and the effective dose was found to be 3 mg/kg. We have observed a significant reduction in the ulcer score in rats pretreated with 3 mg of andrographolide/kg body weight. A favourable increase in the pH and decrease in titrable acidity were observed in the gastric fluid of rats pretreated with the test drug. The gastric tissue H(+)-K(+) ATPase and myeloperoxidase activities were elevated in ulcer-induced animals. The elevation in the enzyme activity was significantly minimized in the andrographolide received animals. The antioxidants and mucin levels were significantly maintained in the gastric tissue of drug-pretreated animals. Andrographolide did not produce any toxic effects in normal rats. This study reveals that the ulcer preventive efficacy of andrographolide may probably due to its antioxidant, cytoprotective and antiacid secretory effects.

  3. Hypoxic inactivation of glycogen synthase kinase-3β promotes gastric tumor growth and angiogenesis by facilitating hypoxia-inducible factor-1 signaling.

    Science.gov (United States)

    Ko, Young San; Cho, Sung Jin; Park, Jinju; Choi, Yiseul; Lee, Jae-Seon; Youn, Hong-Duk; Kim, Woo Ho; Kim, Min A; Park, Jong-Wan; Lee, Byung Lan

    2016-09-01

    Since the molecular mechanism of hypoxic adaptation in cancer cells is cell-type specific, we investigated whether glycogen synthase kinase-3β (GSK-3β) activation is involved in hypoxia-induced gastric tumor promotion. Stable gastric cancer cell lines (SNU-638, SNU-484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild-type GSK-3β (WT-GSK-3β) or kinase-dead mutant of GSK-3β (KD-GSK-3β) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK-3β activation in gastric cancer cells. Cell viability and the expressions of HIF-1α protein and VEGF mRNA in gastric cancer cells were higher in KD-GSK-3β transfectants than in WT-GSK-3β transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF-1α activation, and VEGF expression were higher in KD-GSK-3β tumors than in WT-GSK-3β tumors in vivo. In addition, the expression of hypoxia-induced HIF-1α protein was regulated by GSK-3β at the translational level. Our data suggest that GSK-3β is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF-1α/VEGF signaling pathway. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  4. Helicobacter and Gastric Malignancies

    OpenAIRE

    Ferreira, António Carlos; Isomoto, Hajime; Moriyama, Masatsugu; Fujioka, Toshio; Machado, José Carlos; Yamaoka, Yoshio

    2008-01-01

    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 envir...

  5. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    Science.gov (United States)

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

    Directory of Open Access Journals (Sweden)

    S.R. Martins

    2006-02-01

    Full Text Available Cholecystokinin (CCK influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM and cerulein (EC50: 58; 95% CI: 18-281 nM induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 µM in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

  7. Theory of gastric CO2 ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO2 retention.

    Science.gov (United States)

    Dean, Jay B

    2011-02-15

    The theory of gastric CO(2) ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO(2) during respiratory acidosis. Neurons in the cSC, which is a site of CO(2) chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO(2) from blood. CO(2) is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO(2) in the stomach lumen from the reaction between H(+) and HCO(3)(-). Respiratory acidosis and gastric CO(2) distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO(2) upwards by bulk flow along an abdominal-to-esophageal (=intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO(2) is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO(2) ventilation provides explanations for (1) the postprandial increase in expired CO(2) and (2) the negative P(blood - expired)CO₂difference that occurs with increased inspired CO(2). Furthermore, it is postulated that gastric CO(2) ventilation and alveolar CO(2) ventilation are coordinated under dual control by CO(2) chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO(2) chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO(2) elimination. A distributed CO(2

  8. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand.

    Science.gov (United States)

    Saralamma, Venu Venkatarame Gowda; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Yumnam, Silvia; Raha, Suchismita; Heo, Jeong Doo; Lee, Sang Joon; Lee, Won Sup; Kim, Eun Hee; Kim, Gon Sup

    2015-09-18

    Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies' results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

  9. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats.

    Science.gov (United States)

    Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

    2015-01-01

    The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg(-1), intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg(-1) decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3.

  10. Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

    Science.gov (United States)

    Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

    2016-04-30

    DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

  11. Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

    Directory of Open Access Journals (Sweden)

    Felipe Meira de-Faria

    2012-01-01

    Full Text Available Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH, lipid peroxides (LPO, and the activities of glutathione reductase (GR, glutathione peroxidase (GPx, superoxide dismutase (SOD and myeloperoxidase (MPO were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

  12. Evaluation of the marker technique for measurement of exocrine pancreatic secretion rate

    International Nuclear Information System (INIS)

    Rune, S.J.; Worning, H.

    1985-01-01

    A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min. periods. An inert, water-soluble marker ( 58 Co-vitamin B 12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine panreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min. and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspriate did not vary significantly between consecutive 10-min. periods during the last 20 min. of the secretin stimulation period, or during the last 50 min. of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker, concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker, is a closer estimate of the true volume than that obtained by the usual apsiration technique without a volume indicator

  13. Transformation-Induced Relaxation and Stress Recovery of TiNi Shape Memory Alloy

    Directory of Open Access Journals (Sweden)

    Kohei Takeda

    2014-03-01

    Full Text Available The transformation-induced stress relaxation and stress recovery of TiNi shape memory alloy (SMA in stress-controlled subloop loading were investigated based on the local variation in temperature and transformation band on the surface of the tape in the tension test. The results obtained are summarized as follows. (1 In the loading process, temperature increases due to the exothermic martensitic transformation (MT until the holding strain and thereafter temperature decreases while holding the strain constant, resulting in stress relaxation due to the MT; (2 In the unloading process, temperature decreases due to the endothermic reverse transformation until the holding strain and thereafter temperature increases while holding the strain constant, resulting in stress recovery due to the reverse transformation; (3 Stress varies markedly in the initial stage followed by gradual change while holding the strain constant; (4 If the stress rate is high until the holding strain in the loading and unloading processes, both stress relaxation and stress recovery are large; (5 It is important to take into account this behavior in the design of SMA elements, since the force of SMA elements varies even if the atmospheric temperature is kept constant.

  14. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

    Science.gov (United States)

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-11-03

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

  15. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  16. Effects of corn oil on the volatile fatty acids in horses with induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    José Martínez A

    2016-09-01

    Full Text Available Objetive. To determine the influence of corn oil on the volatile fatty acids (VFA concentrations in the gastric juice in horses with phenylbutazone (PBZ induced gastric ulcers and Correlate the gastroscopic findings with the VFA concentrations. Materials and methods. 15 horses were allotted in 3 groups. Group I (control received placebo during first 6 days (induction period and was treated with sucralfate for 2 weeks (treatment period. Groups II and III received PBZ during the induction phase. After 6 days, horses from group II received 70 mL of corn oil /100 kg of body weight/ po, twice a day, for 2 weeks and horses from group III received 90 mL of corn oil/100 kg of body weight/ po, twice a day, for 2 weeks. All horses were examined by gastroscopy at days 0, 7 and 21. The lesions were recorded and classified according to the number and severity. Samples from gastric fluid were taken to measure the concentrations of the acetic, propionic, butyric and lactic acids. Results. Both PBZ protocols produced lesions in the both non-glandular and glandular areas of the stomach. All the treatments produced healing of the injured mucosa glandular. Neither of the two corn oil treatments affected healing of the gastric ulcers located in the non-glandular area. Conclusions. The concentrations of acetic and butyric acids were highest in the gastric juice. The corn oil and sucralfate did not lead to differences in the concentration of acetic acid and butyric acid.

  17. Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

    Directory of Open Access Journals (Sweden)

    Ausama Ayoob Jaccob

    2015-06-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

  18. Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

    Science.gov (United States)

    Beckett, Amber C.; Piazuelo, M. Blanca; Noto, Jennifer M.; Peek, Richard M.; Washington, M. Kay; Algood, Holly M. Scott

    2016-01-01

    Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H. pylori-associated IDA. Mongolian gerbils (either H. pylori infected or uninfected) received a normal diet or one of three diets associated with increased H. pylori virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet), H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that H. pylori infection can cause IDA and that the composition of the diet influences the incidence and severity of H. pylori-induced IDA. PMID:27620719

  19. Ion peening and stress relaxation induced by low-energy atom bombardment of covalent solids

    International Nuclear Information System (INIS)

    Koster, Monika; Urbassek, Herbert M.

    2001-01-01

    Using molecular-dynamics simulation, we study the buildup and relaxation of stress induced by low-energy (≤150 eV) atom bombardment of a target material. The effect is brought out most clearly by using an initially compressed specimen. As target material, we employ Si, based on the Tersoff potential. By varying the bond strength in the potential, we can specifically study its effect on damage production and stress changes. We find that in general, stress is relaxed by the atom bombardment; only for low bombarding energies and strong bonds, atom bombardment increases stress. We rationalize this behavior by considering the role of energized atoms and of recoil-implanted target atoms

  20. IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

    Directory of Open Access Journals (Sweden)

    Jand-Venes Rolim MEDEIROS

    2013-04-01

    Full Text Available Context Hydrogen sulphide (H2S has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g. After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

  1. Ion Transport in Human Pancreatic Duct Epithelium, Capan-1 Cells, Is Regulated by Secretin, VIP, Acetylcholine, and Purinergic Receptors

    DEFF Research Database (Denmark)

    Wang, Jing; Novak, Ivana

    2013-01-01

    OBJECTIVES: The objective of the study was to establish a solid model of polarized epithelium for human pancreatic ducts, where electrical parameters could be measured as indicators of ion transport. Further, we aimed to determine functional expression of several receptors, in particular, puriner...... transport in human pancreatic duct epithelium, Capan-1 cells, is regulated by secretin, VIP, acetylcholine, adenosine, and purinergic P2 receptors; and this human model has a good potential for studies of physiology and pathophysiology of pancreatic duct ion transport....

  2. PIV and CFD studies on analyzing intragastric flow phenomena induced by peristalsis using a human gastric flow simulator.

    Science.gov (United States)

    Kozu, Hiroyuki; Kobayashi, Isao; Neves, Marcos A; Nakajima, Mitsutoshi; Uemura, Kunihiko; Sato, Seigo; Ichikawa, Sosaku

    2014-08-01

    This study quantitatively analyzed the flow phenomena in model gastric contents induced by peristalsis using a human gastric flow simulator (GFS). Major functions of the GFS include gastric peristalsis simulation by controlled deformation of rubber walls and direct observation of inner flow through parallel transparent windows. For liquid gastric contents (water and starch syrup solutions), retropulsive flow against the direction of peristalsis was observed using both particle image velocimetry (PIV) and computational fluid dynamics (CFD). The maximum flow velocity was obtained in the region occluded by peristalsis. The maximum value was 9 mm s(-1) when the standard value of peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The intragastric flow-field was laminar with the maximum Reynolds number (Re = 125). The viscosity of liquid gastric contents hardly affected the maximum flow velocity in the applied range of this study (1 to 100 mPa s). These PIV results agreed well with the CFD results. The maximum shear rate in the liquid gastric contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow-field in solid-liquid gastric contents containing model solid food particles (plastic beads). The direction of velocity vectors was influenced by the presence of the model solid food particle surface. The maximum flow velocity near the model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1). The maximum shear rate around the model solid food particles was low, with a value of up to 20 s(-1).

  3. Milrinone relaxes pulmonary veins in guinea pigs and humans.

    Directory of Open Access Journals (Sweden)

    Annette D Rieg

    Full Text Available INTRODUCTION: The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH. However, its action on pulmonary veins (PVs is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs and humans. MATERIAL AND METHODS: Precision-cut lung slices (PCLS were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL. RESULTS: In the IPL (GP, milrinone (10 µM lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP, milrinone relaxed naïve and pre-constricted PVs (120% and this relaxation was attenuated by inhibition of protein kinase G (KT 5823, adenyl cyclase (SQ 22536 and protein kinase A (KT 5720, but not by inhibition of NO-synthesis (L-NAME. In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+- and Kv-channels. Human PVs also relaxed to milrinone (121%, however only if pre-constricted. DISCUSSION: Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

  4. Milrinone relaxes pulmonary veins in guinea pigs and humans.

    Science.gov (United States)

    Rieg, Annette D; Suleiman, Said; Perez-Bouza, Alberto; Braunschweig, Till; Spillner, Jan W; Schröder, Thomas; Verjans, Eva; Schälte, Gereon; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

    2014-01-01

    The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of K ATP-, BK Ca (2+)- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on K ATP-, BK Ca (2+)- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

  5. Sinularin Induces Apoptosis through Mitochondria Dysfunction and Inactivation of the pI3K/Akt/mTOR Pathway in Gastric Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Jen Wu

    2016-07-01

    Full Text Available Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-19

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

  7. The effects of progressive muscle relaxation and autogenic relaxation on young soccer players' mood states.

    Science.gov (United States)

    Hashim, Hairul Anuar; Hanafi Ahmad Yusof, Hazwani

    2011-06-01

    This study was designed to compare the effects of two different relaxation techniques, namely progressive muscle relaxation (PMR) and autogenic relaxation (AGR) on moods of young soccer players. sixteen adolescent athletes (mean age: 14.1 ± 1.3) received either PMR or AGR training. Using Profile of Mood States- Adolescents, their mood states were measured one week before relaxation training, before the first relaxation session, and after the twelfth relaxation session. Mixed ANOVA revealed no significant interaction effects and no significant main effects in any of the subscales. However, significant main effects for testing sessions were found for confusion, depression, fatigue, and tension subscales. Post hoc tests revealed post-intervention reductions in the confusion, depression, fatigue, and tension subscale scores. These two relaxation techniques induce equivalent mood responses and may be used to regulate young soccer players' mood states.

  8. Fasting does not induce gastric emptying in rats

    OpenAIRE

    Brito,Marcus Vinicius Henriques; Yasojima,Edson Yuzur; Teixeira,Renan Kleber Costa; Houat,Abdallah de Paula; Yamaki,Vitor Nagai; Costa,Felipe Lobato da Silva

    2015-01-01

    PURPOSE: To evaluate the effect of fasting on gastric emptying in mice.METHODS:Twenty-eight mice were distributed into three study groups: a normal group (N=4): normal standard animals; a total fasting group (N=12): subjected to food and water deprivation and a partial fasting group (N=12): subjected to food deprivation only. The fasting groups were subdivided into three subgroups of four animals each, according to the date of euthanasia: 24, 48 and 72 hours. Was analyzed: the gastric volume,...

  9. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    International Nuclear Information System (INIS)

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-01-01

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways

  10. Effect of lithographically-induced strain relaxation on the magnetic domain configuration in microfabricated epitaxially grown Fe81Ga19

    Science.gov (United States)

    Beardsley, R. P.; Parkes, D. E.; Zemen, J.; Bowe, S.; Edmonds, K. W.; Reardon, C.; Maccherozzi, F.; Isakov, I.; Warburton, P. A.; Campion, R. P.; Gallagher, B. L.; Cavill, S. A.; Rushforth, A. W.

    2017-02-01

    We investigate the role of lithographically-induced strain relaxation in a micron-scaled device fabricated from epitaxial thin films of the magnetostrictive alloy Fe81Ga19. The strain relaxation due to lithographic patterning induces a magnetic anisotropy that competes with the magnetocrystalline and shape induced anisotropies to play a crucial role in stabilising a flux-closing domain pattern. We use magnetic imaging, micromagnetic calculations and linear elastic modelling to investigate a region close to the edges of an etched structure. This highly-strained edge region has a significant influence on the magnetic domain configuration due to an induced magnetic anisotropy resulting from the inverse magnetostriction effect. We investigate the competition between the strain-induced and shape-induced anisotropy energies, and the resultant stable domain configurations, as the width of the bar is reduced to the nanoscale range. Understanding this behaviour will be important when designing hybrid magneto-electric spintronic devices based on highly magnetostrictive materials.

  11. Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia

    Directory of Open Access Journals (Sweden)

    F.A. Capeto

    2015-05-01

    Full Text Available Esophageal atresia (EA is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO. Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA, and DOXO with EA (DOXO+EA. Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh. The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P0.05. In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05. No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05. In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

  12. The role of GABA(A) receptors in the control of transient lower oesophageal sphincter relaxations in the dog

    NARCIS (Netherlands)

    Beaumont, H.; Jönsson-Rylander, A.-C.; Carlsson, K.; Pierrou, S.; Ahlefelt, M.; Brändén, L.; Jensen, J.; Boeckxstaens, G. E.; Lehmann, A.

    2008-01-01

    BACKGROUND AND PURPOSE: Transient lower oesophageal sphincter relaxations (TLESRs) are triggered by activation of mechanosensitive gastric vagal afferents and are the major cause of gastroesophageal reflux and therefore an important target for therapeutic intervention in gastroesophageal reflux

  13. Beta2-adrenoceptor-mediated tracheal relaxation induced by higenamine from Nandina domestica Thunberg.

    Science.gov (United States)

    Tsukiyama, Muneo; Ueki, Takuro; Yasuda, Yoichi; Kikuchi, Hiroko; Akaishi, Tatsuhiro; Okumura, Hidenobu; Abe, Kazuho

    2009-10-01

    The fruit of Nandina domestica Thunberg (ND, Berberidaceae) has been used to improve cough and breathing difficulties in Japan for many years, but very little is known about the constituent of ND responsible for this effect. We have recently reported that the crude extract from ND (NDE) inhibits histamine- and serotonin-induced contraction of isolated guinea pig trachea, and the inhibitory activity was not explained by nantenine, a well-known alkaloid isolated from ND. To explore other constituent(s) of NDE with tracheal smooth muscle relaxant activity, we fractionated NDE and assessed the pharmacological effects of the fractions using isolated guinea pig tracheal ring preparations. NDE was introduced into a polyaromatic absorbent resin column and stepwise eluted to yield five fractions, among which only the 40 % methanol fraction was active in relaxing tracheal smooth muscle precontracted with histamine. Further separation of the 40 % methanol fraction with high-performance liquid chromatography yielded multiple subfractions, one of which was remarkably active in relaxing histamine-precontracted trachea. Chemical analysis with a time-of-flight mass spectrometer and nuclear magnetic resonance spectrometer identified the constituent of the most active subfraction as higenamine, a benzyltetrahydroisoquinoline alkaloid. The potency and efficacy of the active constituent from NDE in relaxing trachea were almost equivalent to synthetic higenamine. In addition, the effect of the active constituent from NDE was competitively inhibited by the selective beta (2)-adrenoceptor antagonist ICI 118,551. These results indicate that the major constituent responsible for the effect of NDE is higenamine, which probably causes the tracheal relaxation through stimulation of beta (2) adrenoceptors. Georg Thieme Verlag KG Stuttgart-New York.

  14. The Effects of Progressive Muscle Relaxation and Autogenic Relaxation on Young Soccer Players’ Mood States

    Science.gov (United States)

    Hashim, Hairul Anuar; Hanafi@Ahmad Yusof, Hazwani

    2011-01-01

    Purpose This study was designed to compare the effects of two different relaxation techniques, namely progressive muscle relaxation (PMR) and autogenic relaxation (AGR) on moods of young soccer players. Methods Sixteen adolescent athletes (mean age: 14.1 ± 1.3) received either PMR or AGR training. Using Profile of Mood States- Adolescents, their mood states were measured one week before relaxation training, before the first relaxation session, and after the twelfth relaxation session. Results Mixed ANOVA revealed no significant interaction effects and no significant main effects in any of the subscales. However, significant main effects for testing sessions were found for confusion, depression, fatigue, and tension subscales. Post hoc tests revealed post-intervention reductions in the confusion, depression, fatigue, and tension subscale scores. Conclusion These two relaxation techniques induce equivalent mood responses and may be used to regulate young soccer players’ mood states. PMID:22375225

  15. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion

    DEFF Research Database (Denmark)

    El-Ouaghlidi, Andrea; Rehring, Erika; Holst, Jens Juul

    2007-01-01

    BACKGROUND/AIMS: Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The present study asked whether vildagliptin accentuates glibenclamide-induced hy...

  16. Thermally induced magnetic relaxation in square artificial spin ice

    Science.gov (United States)

    Andersson, M. S.; Pappas, S. D.; Stopfel, H.; Östman, E.; Stein, A.; Nordblad, P.; Mathieu, R.; Hjörvarsson, B.; Kapaklis, V.

    2016-11-01

    The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice - we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

  17. Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

    Science.gov (United States)

    Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

    2011-10-15

    Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

  18. Advances in Understanding How Heavy Metal Pollution Triggers Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wenzhen Yuan

    2016-01-01

    Full Text Available With the development of industrialization and urbanization, heavy metals contamination has become a major environmental problem. Numerous investigations have revealed an association between heavy metal exposure and the incidence and mortality of gastric cancer. The mechanisms of heavy metals (lead, cadmium, mercury, chromium, and arsenic contamination leading to gastric cancer are concluded in this review. There are four main potential mechanisms: (1 Heavy metals disrupt the gastric mucosal barrier by decreasing mucosal thickness, mucus content, and basal acid output, thereby affecting the function of E-cadherin and inducing reactive oxygen species (ROS damage. (2 Heavy metals directly or indirectly induce ROS generation and cause gastric mucosal and DNA lesions, which subsequently alter gene regulation, signal transduction, and cell growth, ultimately leading to carcinogenesis. Exposure to heavy metals also enhances gastric cancer cell invasion and metastasis. (3 Heavy metals inhibit DNA damage repair or cause inefficient lesion repair. (4 Heavy metals may induce other gene abnormalities. In addition, heavy metals can induce the expression of proinflammatory chemokine interleukin-8 (IL-8 and microRNAs, which promotes tumorigenesis. The present review is an effort to underline the human health problem caused by heavy metal with recent development in order to garner a broader perspective.

  19. A three-dimensional relaxation model for calculation of atomic mixing and topography changes induces by ion beams

    International Nuclear Information System (INIS)

    Collins, R.; Perez-Martin, A.M.C.; Dominguez-Vazquez, J.; Jimenez-Rodriguez, J.J.

    1994-01-01

    A simple model for three-dimensional material relaxation associated with atomic mixing is presented. The relaxation of the solid to accommodate the extra effective displacement volume Ω of an implanted or relocated atom is modelled by treating the surrounding solid as an incompressible medium. This leads to a tractable general formalism which can be used to predict implant distribution and changes in surface topography induced by ion beams, both in monatomic and multicomponent targets. The two-component case is discussed in detail. (orig.)

  20. Anisotropy of the nuclear magnetic relaxation times induced in solid 3He by modulation of the dipolar interactions

    International Nuclear Information System (INIS)

    Deville, G.

    1976-01-01

    Anisotropic nuclear relaxation times have been measured in solid 3 He samples grown at constant pressure, in the Larmor frequency range 1.5MHz-5MHz where the main relaxation mechanism is the modulation of the dipolar interaction by exchange or by motion of the vacancies. The second order calculation made by Harris for the exchange induced relaxation regime is extended to the regime where vacancy motion dominates. The theory is further refined by considering the fourth moment anisotropy effect on the spectral densities. This latter calculation yields a frequency dependent anisotropic contribution to T 1 which agrees qualitatively with the data, unlike the simpler results by Harris [fr

  1. Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.

    Science.gov (United States)

    Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

    2009-01-01

    Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. Copyright 2009 S. Karger AG, Basel.

  2. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

    Science.gov (United States)

    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  3. Aspirin-Induced Gastric Lesions Alters EGFR and PECAM-1 Immunoreactivity in Wistar Rats: Modulatory Action of Flavonoid Fraction of Musa Paradisiaca.

    Science.gov (United States)

    Alese, Margaret Olutayo; Adewole, Stephen Olarinde; Akinwunmi, Kemi Feyisayo; Omonisi, Abidemi Emmanuel; Alese, Oluwole Ojo

    2017-08-15

    In this study, Epithelial Growth Factor Receptor and Platelet Endothelial Cell Adhesion Molecule-1 were localised to investigate the healing effects of a flavonoid-rich fraction of M. paradisiaca fruit in the gastric corpus of Wistar rats following aspirin-induced gastric lesion. Mature, unripe fruits of M. paradisiaca were peeled; air dried, pulverised, extracted with 70% methanol, concentrated and partitioned. Ninety male Wistar rats were randomly assigned into 6 groups of 15 rats each. The gastric lesion was induced in groups B, C, D, E and F rats by administration of 400 mg/kg aspirin in distilled water. Group A received distilled water. After 24 hours, flavonoid fraction of M. paradisiaca was administered to groups C, D and E at 100, 200 and 400 mg/kg respectively for 21 days. Group F rats received omeprazole at 1.8 mg/kg for 21 days. Five rats from each group were anaesthetized with ketamine on days 14, 21 and 28. Gastric tissues were excised and fixed in Neutral buffered formalin. This was followed by paraffin wax embedding method and sections stained with haematoxylin and eosin and for immunolocalisation of EGFR and PECAM-1. Data were analysed using descriptive and inferential statistics. There was a significant difference in the ulcer index in the corpus of control and treated rats throughout the experimental period (p = 0.0001). H&E stained sections showed a gradual restoration of the epithelial lining in the treated groups. Immunohistochemical examination showed that M. paradisiaca significantly increased (p Musa paradisiaca in attenuating the damaging effects of aspirin on the gastric mucosa was observed as there was a significantly increased reactivity for EGFR and PECAM-1 in the gastric corpus in a dose-dependent manner.

  4. Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer.

    Science.gov (United States)

    Kalayci, Mehmet; Kocdor, Mehmet Ali; Kuloglu, Tuncay; Sahin, İbrahim; Sarac, Mehmet; Aksoy, Aziz; Yardim, Meltem; Dalkilic, Semih; Gursu, Onur; Aydin, Suna; Akkoc, Ramazan Fazil; Ugras, Meltem; Artas, Gokhan; Ozercan, İbrahim Hanifi; Ugur, Kader; Aydin, Suleyman

    2017-10-01

    The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer+NS); Group III (5mg/kg sildenafil citrate, low dose); Group IV (10mg/kg sildenafil citrate, high dose); Group V (0.6mg/kg heparin, low dose); Group VI (6mg/kg heparin, high dose); Group VII (20nmol/kg des-acyl ghrelin); Group VIII (40nmol/kg des-acyl ghrelin); Group IX (4nmol/kg acyl ghrelin); Group X (8nmol/kg acly ghrelin); Group XI (20pmol/kg Nesfatin-1); Group XII (15nmol/kg Obestatin) and Group XIII (5nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A Polysaccharide Isolated from Mycelia of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) Induced Apoptosis in Precancerous Human Gastric Cells.

    Science.gov (United States)

    Wang, Mingxing; Zhang, Yanqiu; Xiao, Xulang; Xu, Duoduo; Gao, Yang; Gao, Qipin

    2017-01-01

    Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.

  6. Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

    Science.gov (United States)

    Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

    2013-11-30

    l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

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    Sachin MANOCHA

    Full Text Available ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed

  8. ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.

    Science.gov (United States)

    Manocha, Sachin; Lal, Dushyant; Venkataraman, Subramanian

    2016-01-01

    Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In

  9. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond

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    Tetsuya Tsukamoto

    2017-08-01

    Full Text Available Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

  11. Relaxation effect of abacavir on rat basilar arteries.

    Directory of Open Access Journals (Sweden)

    Rachel Wai Sum Li

    Full Text Available The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels.The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate.Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries.Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to

  12. Pilot Investigation of a Virtual Gastric Band Hypnotherapy Intervention.

    Science.gov (United States)

    Greetham, Stephanie; Goodwin, Sarah; Wells, Liz; Whitham, Claire; Jones, Huw; Rigby, Alan; Sathyapalan, Thozhukat; Reid, Marie; Atkin, Stephen

    2016-01-01

    This 24-week-long pilot investigation of 30 men and women with a BMI > 27 kg/m(2) aimed to determine whether virtual gastric band (VGB) hypnotherapy has an effect on weight loss in overweight adults, compared to relaxation hypnotherapy and a self-directed diet. Levels of weight loss and gain ranged from -17 kg to +4.7 kg in the VGB hypnotherapy group and -9.3 kg to +7.8 kg in the relaxation group. There was no significant difference between VGB hypnotherapy as a main effect on weight loss, (X(2) = 0.67, p = .41, df = 1) and there was no evidence of differential weight loss over time, (X(2) = 4.2, p = .64, df = 6). Therefore, the authors conclude that there was no significant difference between VGB hypnotherapy and the relaxation hypnotherapy.

  13. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    Science.gov (United States)

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

  14. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Ma, Ning; Adachi, Yukihiko; Hiraku, Yusuke; Horiki, Noriyuki; Horiike, Shinichirou; Imoto, Ichiro; Pinlaor, Somchai; Murata, Mariko; Semba, Reiji; Kawanishi, Shosuke

    2004-01-01

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  15. Influence of plant-originated gastroproteciive and antiulcer substances on gastric mucosal repair.

    Science.gov (United States)

    Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Brzozowski, T; Gzhegotsky, M R

    2004-01-01

    Fundamental basis of cellular and molecular mechanisms involved in mucosal injury and repair in gastrointestinal tract helps to develop new therapeutic approaches to various gut mucosal injury- related diseases. The study was aimed to assess the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulceric activities and to deteminate if these effects are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically. The following plant-originated substances were considered: Solon, capsaicin, grapefruit-seed extract and amaranth. The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). male Wistar rats, weighing 180-220 g fasted for 24 h before the study, 100% ethanol was applied ig to induced gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by an increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment-with L-NNA. Plant-originated substances are highly gastroprotective probably due to enhancement of the expression of NOS I, NO release and an increase in gastric microcirculation.

  16. Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis.

    Science.gov (United States)

    Feichtinger, René G; Neureiter, Daniel; Skaria, Tom; Wessler, Silja; Cover, Timothy L; Mayr, Johannes A; Zimmermann, Franz A; Posselt, Gernot; Sperl, Wolfgang; Kofler, Barbara

    2017-01-01

    Switching of cellular energy production from oxidative phosphorylation (OXPHOS) by mitochondria to aerobic glycolysis occurs in many types of tumors. However, the significance of this switching for the development of gastric carcinoma and what connection it may have to Helicobacter pylori infection of the gut, a primary cause of gastric cancer, are poorly understood. Therefore, we investigated the expression of OXPHOS complexes in two types of human gastric carcinomas ("intestinal" and "diffuse"), bacterial gastritis with and without metaplasia, and chemically induced gastritis by using immunohistochemistry. Furthermore, we analyzed the effect of HP infection on several key mitochondrial proteins. Complex I expression was significantly reduced in intestinal type (but not diffuse) gastric carcinomas compared to adjacent control tissue, and the reduction was independent of HP infection. Significantly, higher complex I and complex II expression was present in large tumors. Furthermore, higher complex II and complex III protein levels were also obvious in grade 3 versus grade 2. No differences of OXPHOS complexes and markers of mitochondrial biogenesis were found between bacterially caused and chemically induced gastritis. Thus, intestinal gastric carcinomas, but not precancerous stages, are frequently characterized by loss of complex I, and this pathophysiology occurs independently of HP infection.

  17. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-15

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA{sub B} receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA{sub B} receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA{sub B} receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  18. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    International Nuclear Information System (INIS)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de

    2015-01-01

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA B receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA B receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA B receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN

  19. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Wilson Ranu Ramirez Nunez

    2015-02-01

    Full Text Available Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN of the hypothalamus in GE and gastric compliance (GC in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular. Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  20. Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Brewer, Jonathan R

    2016-01-01

    -activated K(+) -channels, but markedly blunted by catalase during ET-1-induced contraction. This catalase-sensitive relaxation was not modified by inhibitors of NADPH oxidases or allopurinol. Exogenous H2 O2 caused significantly larger relaxation of ET-1- than K(+) - or U46619-induced contraction...... in the presence of inhibitors of other endothelium-derived relaxing factors. Catalase-sensitive staining of cellular reactive oxygen species with CellROX Deep Red was significantly increased in presence of both 1 μM BK and 2 nM ET-1 but not either peptide alone. CONCLUSIONS AND IMPLICATIONS: In patient resistance...

  1. Evidence for the gastric cytoprotective effect of centrally injected agmatine.

    Science.gov (United States)

    Zádori, Zoltán S; Tóth, Viktória E; Fehér, Ágnes; Philipp, Kirsch; Németh, József; Gyires, Klára

    2014-09-01

    Agmatine (decarboxylated arginine) exerts cytoprotective action in several tissues, such as in the brain, heart or kidneys, but there is still controversy over the effects of agmatine on the gastric mucosa. The aim of the present study was to reveal the potential gastroprotective action of agmatine by using an acid-independent ulcer model to clarify which receptors and peripheral factors are involved in it. Gastric mucosal damage was induced by acidified ethanol. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. It was found that agmatine given intracerebroventricularly (i.c.v., 0.044-220 nmol/rat) significantly inhibited the development of ethanol-induced mucosal damage, while in the case of intraperitoneal injection (0.001-50mg/kg i.p.) it had only a minor effect. The central gastroprotective action of agmatine was completely antagonized by mixed alpha2-adrenoceptor and imidazoline I1 receptor antagonists (idazoxan, efaroxan), but only partially by yohimbine (selective alpha2-adrenoceptor antagonist) and AGN 192403 (selective I1 receptor ligand, putative antagonist). It was also inhibited by the non-selective opioid-receptor antagonist naloxone and the selective δ-opioid receptor antagonist naltrindole, but not by β-funaltrexamine and nor-Binaltorphimine (selective μ- and κ-opioid receptor antagonists, respectively). Furthermore, the effect of agmatine was antagonized by bilateral cervical vagotomy and by pretreatment with indomethacin and NG-nitro-l-arginine. Agmatine also reversed the ethanol-induced reduction of gastric mucosal CGRP and somatostatin content, but did not have any significant effect on gastric motor activity. These results indicate that agmatine given centrally induces gastric cytoprotection, which is mediated by central imidazoline I1 receptors, alpha2-adrenoceptors and δ-opioid receptors. Activation of

  2. Epithelial Regeneration After Gastric Ulceration Causes Prolonged Cell-Type AlterationsSummary

    Directory of Open Access Journals (Sweden)

    Eitaro Aihara

    2016-09-01

    Full Text Available Background & Aims: The peptic ulcer heals through a complex process, although the ulcer relapse often occurs several years later after healing. Our hypothesis is that even after visual evidence of healing of gastric ulceration, the regenerated epithelium is aberrant for an extended interval, increasing susceptibility of the regenerated epithelium to damage and further diseases. Methods: Gastric ulcers were induced in mice by serosal topical application of acetic acid. Results: Gastric ulcers induced by acetic acid visually healed within 30 days. However, regenerated epithelial architecture was poor. The gene profile of regenerated tissue was abnormal, indicating increased stem/progenitor cells, deficient differentiated gastric cell types, and deranged cell homeostasis. Despite up-regulation of PDX1 in the regenerated epithelium, no mature antral cell type was observed. Four months after healing, the regenerated epithelium lacks parietal cells, trefoil factor 2 (TFF2 and (sex-determining region Y-box 9 (SOX9 remain up-regulated deep in the gastric gland, and the Na/H exchanger 2 (a TFF2 effector in gastric healing remains down-regulated. Gastric ulcer healing was strongly delayed in TFF2 knockout mice, and re-epithelialization was accompanied with mucous metaplasia. After Helicobacter pylori inoculum 30 days after ulceration, we observed that the gastric ulcer selectively relapses at the same site where it originally was induced. Follow-up evaluation at 8 months showed that the relapsed ulcer was not healed in H pylori–infected tissues. Conclusions: These findings show that this macroscopically regenerated epithelium has prolonged abnormal cell distribution and is differentially susceptible to subsequent damage by H pylori. Keywords: Gastric Ulcer Healing, Metaplasia, H pylori, SOX9, TFF2, NHE2

  3. Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats.

    Science.gov (United States)

    Itoh, Y H; Noguchi, R

    2000-01-01

    The purpose of this study was to assess the preventive effect of pre-mild whole-body heating (WBH) on gastric ulcer induced by restraint and water-immersion stress. The ulcer index and ulcer area ratio in rats exposed to restraint and water-immersion stress were significantly decreased (p immersion stress alone (p immersion, thereby preventing gastric ulcer formation. Pre-treatment with mild WBH is the safest cytoprotective method through the accumulation of HSP 70f. The concentration of HSP 70f in peripheral lymphocytes may be a useful clinical laboratory indicator for assessing the level of HSP 70f as having cytoprotective activity.

  4. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    International Nuclear Information System (INIS)

    Becker, Jan C.; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

    2006-01-01

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection

  5. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Jan C [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

    2006-07-07

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

  6. Gastric angiogenesis and Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    I. D. Pousa

    Full Text Available The formation of new blood vessels seen in conditions commonly associated with Helicobacter pylori (H. pylori infection, including gastritis, peptic ulcer, and gastric carcinoma, prompts consideration of a potential relationship between mucosal colonization by this organism and the angiogenic process. H. pylori directly or indirectly damages endothelial cells, which induces a number of changes in the microvasculature of the gastric mucosa. In H. pylori-associated conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is an increased concentration of angiogenic factors, and subsequently a formation of new blood vessels. However, this early angiogenesis -which is activated to repair the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and ulcer healing is thus delayed. This may be due to the antiproliferative action of this organism on endothelial cells. While the angiogenic process becomes inhibited in infected patients with peptic ulcer, it remains seemingly active in those with gastritis or gastric cancer. This fact is in support of the notion suggested by various studies that peptic ulcer and gastric cancer are mutually excluding conditions. In the case of gastric cancer, neoangiogenesis would enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and metastatic spread.

  7. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

    Science.gov (United States)

    Toti, Luca; Travagli, R Alberto

    2014-11-15

    Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. Copyright © 2014 the American Physiological Society.

  8. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  9. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  10. Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features

    International Nuclear Information System (INIS)

    Feng, Chang Wei; Wang, Li Dong; Jiao, Lian Hua; Liu, Bin; Zheng, Shu; Xie, Xin Ji

    2002-01-01

    The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized. The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China. The positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining

  11. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repai...

  12. [Expression of tumor necrosis factor-like weak inducer of apoptosis in patients with gastric cancer and its relationship with nutritional status].

    Science.gov (United States)

    Lu, Hang; Sun, Yuanshui

    2016-10-25

    To investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the serum and the rectus abdominis muscle in patients with gastric cancer and its relationship with the nutritional status. Method Clinical data of 102 patients with gastric cancer (gastric cancer group) and 53 patients with benign abdominal disease (control group) who were admitted to Zhejiang Province People's Hospital from January 2008 to October 2013 were analyzed retrospectively. Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum expression of TWEAK. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expression of TWEAK in the rectus abdominis muscle. Relationship between TWEAK expression and nutritional status of gastric cancer patients was examined. The relative expression level of TWEAK protein in serum of gastric cancer group and control group was 0.403±0.065 and 0.148±0.036 respectively. The relative expression of TWEAK mRNA in the rectus abdominis muscle tissue was 0.313±0.089 (gastric cancer group) and 0.118±0.005 (control group). The relative expression of TWEAK protein in the rectus abdominis muscle tissue was 0.197±0.064 (gastric cancer group) and 0.066±0.014 (control group), and the differences were statistically significant (both P=0.000). The high expression of TWEAK (high than median) in rectus abdominis muscle of gastric cancer patients was related to the percentage of more than 10% decline in body weight (P=0.000), the small percentage of ideal body weight at the time of admission (P=0.000), BMInutritional risk screening score (P=0.000), lower prognostic nutrition index (P=0.000) and serum albumin gastric cancer patients up-regulates compared to non-tumor patients. The expression level of TWEAK in the rectus abdominis muscle of gastric cancer patients is closely related to poor nutritional status, suggesting that TWEAK may play a key role in the process of

  13. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

  14. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  15. Effect of secretin and inhibitors of HCO3-/H+ transport on the membrane voltage of rat pancreatic duct cells

    DEFF Research Database (Denmark)

    Novak, I; Pahl, C

    1993-01-01

    depolarized the basolateral membrane voltage, Vbl, by up to 35 mV (n = 37); a half-maximal response was obtained at 3 x 10(-11) mol/l. In unstimulated ducts a decrease in the luminal Cl- concentration (120 to 37 mmol/l) had a marginal effect on Vbl, but after maximal secretin stimulation it evoked a 14 +/- 2......), respectively. The fractional resistance of the basolateral membrane (FRbl) doubled, and the depolarizing responses to changes in bath K+ concentrations (5 to 20 mmol/l) decreased from 22 +/- 1 to 11 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)...

  16. Development of gastric cancer associated with Helicobacter pylori infection.

    Science.gov (United States)

    Sugiyama, Toshiro

    2004-09-01

    Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

  17. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    International Nuclear Information System (INIS)

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  18. Effect of Evodiamine on Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901 in Vitro

    Directory of Open Access Journals (Sweden)

    LIU Shao-ping

    2014-09-01

    Full Text Available Objective: To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods: After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT assay while apoptosis and cell-cycle phase distribution using flow cytometry. Results: In 0.01~30.00 μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16 μg/mL; the apoptosis rate was increased from 3.4% to 7.0%, 13.8% and 36.3% at concentrations of 0, 0.5, 1.5 and 30 μg/mL of evodiamine, respectively; the percentage of cells accumulated in G2/M phase was increased from 17.26% to 98.92% in the cells treated with evodiamine for 24 h in 0.01~30.00 μg/mL range of concentrations. Conclusion: Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.

  19. Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats.

    Science.gov (United States)

    Tuluce, Yasin; Ozkol, Halil; Koyuncu, Ismail; Ine, Hatice

    2011-09-01

    The aim of this study was to determine the antiulcer and antioxidant activities of Centaurium erythraea L (small centaury) in aspirin (ASA) induced acute gastric ulcer model. The gastroprotective effect of the 50% aqueous-ethanolic small centaury (SC) extract was investigated in rats at a dose of ASA 200 mg/kg body weight. Twenty-one Sprague-Dawley albino rats were divided into three groups of seven rats each as follows: (1) control group; (2) acute ASA-treated group and (3) ASA plus SC group. At the end of the 4-h drug administration, ulcer index, oxidant and antioxidant levels were measured and compared between the groups. The percentage of lesion area to total gastric surface area (ulcer index) was significantly reduced (77%) in ASA plus SC group as compared with acute ASA-treated group. The oral administration of ASA decreased catalase (CAT), reduced glutathione (GSH), and increased lipid peroxidation (LPO) levels. Although myeloperoxidase (MPO) activity was increased by ASA, it was found to be lower in the ASA plus SC group. GSH and Vitamin A levels were determined higher in the ASA plus SC group compared with ASA group. These results suggest that SC extract protects against ASA-induced damage due to its antioxidizing activity.

  20. Host pathogen interactions in Helicobacter pylori related gastric cancer

    Science.gov (United States)

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  1. Autophagy Facilitates Metadherin-Induced Chemotherapy Resistance Through the AMPK/ATG5 Pathway in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Guoqing Pei

    2018-04-01

    Full Text Available Background/Aims: Metadherin (MTDH is overexpressed in some malignancies and enhances drug resistance; however, its role in gastric cancer (GC and the underlying mechanisms remain largely unexplored. Here, we explore the mechanism by which MTDH induces drug resistance in GC. Methods: We analysed the level of MTDH in GC and adjacent normal gastric mucosal tissues by real-time quantitative PCR (q-PCR. We also analysed the level of autophagy by western blot analysis, confocal microscopy, and transmission electron microscopy after MTDH knockdown and overexpression, and examined fluorouracil (5-FU resistance by Cell Counting Kit-8 at the same time. Finally, GC patient-derived xenograft tumours were used to demonstrate 5-FU resistance. An AMPK pathway inhibitor was applied to determine the molecular mechanisms of autophagy. Results: MTDH expression was significantly increased in the GC specimens compared with that in the adjacent normal gastric mucosal tissues. Further study showed a positive correlation between the expression level of MTDH and 5-FU resistance. MTDH overexpression in MKN45 cells increased the levels of P-glycoprotein (P-gp and promoted 5-FU resistance, while inhibition of MTDH showed the opposite result. The simultaneous inhibition of autophagy and overexpression of MTDH decreased the levels of P-gp and inhibited 5-FU resistance. Moreover, MTDH induced AMPK phosphorylation, regulated ATG5 expression, and finally influenced autophagy, suggesting that MTDH may activate autophagy via the AMPK/ATG5 signalling pathway. Our findings reveal a unique mechanism by which MTDH promotes GC chemoresistance and show that MTDH is a potential target for improved chemotherapeutic sensitivity and GC patient survival. Conclusions: MTDH-stimulated cancer resistance to 5-FU may be mediated through autophagy activated by the AMPK/ATG5 pathway in GC.

  2. The relationships between suggestibility, influenceability, and relaxability.

    Science.gov (United States)

    Polczyk, Romuald; Frey, Olga; Szpitalak, Malwina

    2013-01-01

    This research explores the relationships between relaxability and various aspects of suggestibility and influenceability. The Jacobson Progressive Muscle Relaxation procedure was used to induce relaxation. Tests of direct suggestibility, relating to the susceptibility of overt suggestions, and indirect suggestibility, referring to indirect hidden influence, as well as self-description questionnaires on suggestibility and the tendency to comply were used. Thayer's Activation-Deactivation Adjective Check List, measuring various kinds of activation and used as a pre- and posttest, determined the efficacy of the relaxation procedure. Indirect, direct, and self-measured suggestibility proved to be positively related to the ability to relax, measured by Thayer's subscales relating to emotions. Compliance was not related to relaxability. The results are discussed in terms of the aspects of relaxation training connected with suggestibility.

  3. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean......BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM......: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...

  4. The use of (double) relaxation oscillation SQUIDs as a sensor

    NARCIS (Netherlands)

    van Duuren, M.J.; Brons, G.C.S.; Kattouw, H.; Flokstra, Jakob; Rogalla, Horst

    1997-01-01

    Relaxation Oscillation SQUIDs (ROSs) and Double Relaxation Oscillation SQUIDs (DROSs) are based on relaxation oscillations that are induced in hysteretic dc SQUIDs by an external L-R shunt. The relaxation frequency of a ROS varies with the applied flux Φ, whereas the output of a DROS is a dc

  5. A new technique for continuous measurement and recording of gastric potential difference in the rat: evaluation of NSAID-induced gastric mucosal damage.

    Science.gov (United States)

    Scarpignato, C; Corradi, C; Gandolfi, M A; Galmiche, J P

    1995-10-01

    Disruption of the gastric mucosal barrier by the so-called "barrier breakers" such as ethanol, aspirin, and bile is associated with an increase in gastric potential difference (GPD), that is, a decrease in its negativity. Because a good correlation between the degree of histological damage and changes in GPD has been observed, this parameter has been used increasingly as an index of mucosal integrity. However, the current methodology for measuring GPD is laborious due to the preparation and checking of KCl-agarose bridges prior to each experiment, and calculations--usually handmade--are time-consuming and inaccurate. In this paper, a new method allowing simultaneous measurement and recording of GPD in the rat is described. The method allows a simultaneous recording of intragastric pH and an automatic data analysis. The new technique has been validated by studying mucosal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) (namely indomethacin and droxicam) as well as the mucosal protective activity of an antacid and sucralfate. The similarity between the results obtained in this rat model and those derived from human experiments clearly show that the developed methodology yields results that are predictive for human pharmacology.

  6. Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activatesk-channels of isolated pulmonary artery of rats

    International Nuclear Information System (INIS)

    Eder, Veronique; Gautier, Mathieu; Boissiere, Julien; Girardin, Catherine; Rebocho, Manuel; Bonnet, Pierre

    2004-01-01

    Purpose: To test the effects of irradiation (R*) on the pulmonary artery (PA). Methods and materials: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min -1 ) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10 -4 M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. Results: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted rings exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 ± 17% (n = 13). This was totally blocked by L-NAME (10 -4 M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. Conclusion: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels

  7. Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis

    Science.gov (United States)

    Skaria, Tom; Wessler, Silja; Cover, Timothy L.; Posselt, Gernot; Sperl, Wolfgang; Kofler, Barbara

    2017-01-01

    Switching of cellular energy production from oxidative phosphorylation (OXPHOS) by mitochondria to aerobic glycolysis occurs in many types of tumors. However, the significance of this switching for the development of gastric carcinoma and what connection it may have to Helicobacter pylori infection of the gut, a primary cause of gastric cancer, are poorly understood. Therefore, we investigated the expression of OXPHOS complexes in two types of human gastric carcinomas (“intestinal” and “diffuse”), bacterial gastritis with and without metaplasia, and chemically induced gastritis by using immunohistochemistry. Furthermore, we analyzed the effect of HP infection on several key mitochondrial proteins. Complex I expression was significantly reduced in intestinal type (but not diffuse) gastric carcinomas compared to adjacent control tissue, and the reduction was independent of HP infection. Significantly, higher complex I and complex II expression was present in large tumors. Furthermore, higher complex II and complex III protein levels were also obvious in grade 3 versus grade 2. No differences of OXPHOS complexes and markers of mitochondrial biogenesis were found between bacterially caused and chemically induced gastritis. Thus, intestinal gastric carcinomas, but not precancerous stages, are frequently characterized by loss of complex I, and this pathophysiology occurs independently of HP infection. PMID:28744336

  8. Magnetic relaxation induced by transverse flux shaking in MgB{sub 2} superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Luzuriaga, J; Nieva, G; Serquis, A; Serrano, G [Centro Atomico Bariloche, CNEA, Instituto Balseiro, UNC (Argentina); BadIa-Majos, A [Departamento de Fisica de la Materia Condensada-ICMA, Universidad de Zaragoza-CSIC (Spain); Giordano, J L [Departamento de Ciencias de la IngenierIa, Universidad de Talca (Chile); Lopez, C [Departamento de Matematicas, Universidad de Alcala de Henares (Spain)], E-mail: luzuriag@cab.cnea.gov.ar

    2009-01-15

    We report on measurements and numerical simulations of the behavior of MgB{sub 2} superconductors when magnetic field components are applied along mutually perpendicular directions. By closely matching the geometry in simulations and measurements, full quantitative agreement is found. The critical state theory and a single phenomenological law, i.e. the field dependence of the critical current density J{sub c}(B), are sufficient for a full quantitative description of the measurements. These were performed in thick strips of carbon nanotube doped MgB{sub 2} samples. Magnetization was measured in two orthogonal directions using a SQUID magnetometer. Magnetic relaxation effects induced by the application of an oscillatory perpendicular field were observed and simulated numerically. The measurements confirm the numerical predictions, that two relaxation regimes appear, depending on the amplitude of the applied magnetic field. The overall agreement constitutes a convincing validation of the critical state model and the numerical procedures used.

  9. Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

    Science.gov (United States)

    Auger, Cyril; Pollet, Brigitte; Arnold, Cécile; Marx, Céline; Schini-Kerth, Valérie B

    2015-01-01

    Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86 g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14 g GAE/L) and one active blend of red fruit juices (3.48 g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

  10. Carbon monoxide releasing molecule-2 ameliorates IL-1β-induced IL-8 in human gastric cancer cells

    International Nuclear Information System (INIS)

    Lian, Sen; Xia, Yong; Ung, Trong Thuan; Khoi, Pham Ngoc; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2016-01-01

    Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1β induced the translocation of p47 phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1β activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1β-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1β-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1β-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.

  11. [Gastroprotective effect of honey in Holtzman rats with piroxicam-induced gastric ulcer].

    Science.gov (United States)

    Roldán-Rodríguez, Aníbal Enrique; Vega-Quispe, Erick Joel; Silva-Ocas, Isabel; Lemus-Arteaga, Kevin Edward; Gonzales-Saldaña, Jaime Gilberto; Ruiz-Urbina, Franklyn Norwich; Urtecho-Gaitan, Iván Freddy; Zamora-Mostacero, Víctor Edwin; Vargas-Ferrer, Juan Edder; Valverde-Quezada, Gillmari Juliza; Vásquez-Sandoval, Kevin Oswaldo; Huamán-Saavedra, Juan Jorge

    2016-01-01

    To determine the effect of treatment with honey in piroxicam-induced gastric ulcer in Holtzman rats. 48 eight-week old female Holtzman rats, weights between 100 and 200 grams, were divided into 6 treatment groups as follow: Group A: water; Group B: piroxicam (30 mg/kg); Group C: omeprazole (5 mg/kg) and piroxicam (30 mg/kg); Group D: honey (2.5 g/kg) and piroxicam (30 mg/kg); Group E: honey (5 g/kg) and piroxicam (30 mg/kg); Group F: honey (7.5 g/kg) and piroxicam (30 mg/kg). Macroscopic studies, using Scion Image, and microscopic histological section of gastric mucosa were performed after the interventions. The results of the macroscopic studies showed statistically significant differences for both doses of honey at 6 g/kg and 7.5 g/kg when compared to piroxicam (p=0.016 and p=0.001 respectively) and the gastroprotective effect was similar when compared to omeprazole (p>0.05). Microscopic studies showed statistically significant differences only for dose at 7.5 g/kg when compared to piroxicam (p=0.0018) and the gastroprotective effect was similar to omeprazole (p=1). Dose of honey at 7.5 g/kg showed gastroprotective effect at microscopic and macroscopic studies when compared to omeprazole.

  12. Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

    Science.gov (United States)

    Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

    2017-07-14

    BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

  13. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Hiroto Kinoshita

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/- mice with wild-type (WT mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/- mice, compared with WT mice. Impaired tumor development in IL-6(-/- mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1 receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.

  14. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  15. Metaplasia in the Stomach-Precursor of Gastric Cancer?

    Science.gov (United States)

    Kinoshita, Hiroto; Hayakawa, Yoku; Koike, Kazuhiko

    2017-09-27

    Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term Helicobacter pylori infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by H. pylori infection.

  16. Metaplasia in the Stomach—Precursor of Gastric Cancer?

    Directory of Open Access Journals (Sweden)

    Hiroto Kinoshita

    2017-09-01

    Full Text Available Despite a significant decrease in the incidence of gastric cancer in Western countries over the past century, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Most human gastric cancers develop after long-term Helicobacter pylori infection via the Correa pathway: the progression is from gastritis, atrophy, intestinal metaplasia, dysplasia, to cancer. However, it remains unclear whether metaplasia is a direct precursor of gastric cancer or merely a marker of high cancer risk. Here, we review human studies on the relationship between metaplasia and cancer in the stomach, data from mouse models of metaplasia regarding the mechanism of metaplasia development, and the cellular responses induced by H. pylori infection.

  17. Physiological blunting during pregnancy extends to induced relaxation.

    Science.gov (United States)

    DiPietro, Janet A; Mendelson, Tamar; Williams, Erica L; Costigan, Kathleen A

    2012-01-01

    There is accumulating evidence that pregnancy is accompanied by hyporesponsivity to physical, cognitive, and psychological challenges. This study evaluates whether observed autonomic blunting extends to conditions designed to decrease arousal. Physiological and psychological responsivity to an 18-min guided imagery relaxation protocol in healthy pregnant women during the 32nd week of gestation (n=54) and non-pregnant women (n=28) was measured. Data collection included heart period (HP), respiratory sinus arrhythmia (RSA), tonic and phasic measures of skin conductance (SCL and NS-SCR), respiratory period (RP), and self-reported psychological relaxation. As expected, responses to the manipulation included increased HP, RSA, and RP and decreased SCL and NS-SCR, followed by post-manipulation recovery. However, responsivity was attenuated for all physiological measures except RP in pregnant women, despite no difference in self-reported psychological relaxation. Findings support non-specific blunting of physiological responsivity during pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow cytometry and western blot were used to examine the morpholog, proliferation and apoptosis of human gastric cancer SGC-7901 cells when they were affected by polysaccharide. Results show that ...

  19. Veronicastrum axillare Alleviates Ethanol-Induced Injury on Gastric Epithelial Cells via Downregulation of the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Wei-chun Zhao

    2017-01-01

    Full Text Available We used human gastric epithelial cells (GES-1 line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway.

  20. Current evidence for a role of GLP-1 in Roux-en-Y gastric bypass-induced remission of type 2 diabetes

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Vilsbøll, T; Knop, F K

    2012-01-01

    Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM......-induced remission of T2DM are lacking. This article critically evaluates the current evidence for a role of GLP-1 in RYGB-induced remission of T2DM.......Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM...... antidiabetic effects of GLP-1 are thought to be key mediators in RYGB-induced remission of T2DM. However, the published studies on the impact of RYGB on GLP-1 secretion are few, small and often not controlled properly. Furthermore, mechanistic studies delineating the role of endogenous GLP-1 secretion in RYGB...

  1. Importance of Second-look Endoscopy on an Empty Stomach for Finding Gastric Bezoars in Patients with Gastric Ulcers.

    Science.gov (United States)

    Iwamuro, Masaya; Tanaka, Shouichi; Moritou, Yuki; Inaba, Tomoki; Higashi, Reiji; Kusumoto, Chiaki; Yunoki, Naoko; Ishikawa, Shin; Okamoto, Yuko; Kawai, Yoshinari; Kitada, Ken-Ichi; Takenaka, Ryuta; Toyokawa, Tatsuya; Okada, Hiroyuki

    2017-06-01

     Most gastric bezoars can be treated with endoscopic fragmentation combined with or without cola dissolution, whereas laparotomy or laparoscopic surgery is generally inevitable for small intestinal bezoars because they cause small bowel obstruction. Therefore, early diagnosis and management of gastric bezoars are necessary to prevent bezoar-induced ileus. To investigate the incidence of overlooked gastric bezoars during the initial esophagogastroduodenoscopy, we retrospectively reviewed the cases of 27 patients diagnosed with gastrointestinal bezoars. The bezoars were diagnosed using esophagogastroduodenoscopy (n=25), abdominal ultrasonography (n=1), and barium follow-through examination (n=1). Bezoars were overlooked in 9/25 patients (36.0%) during the initial endoscopy examination because the bezoars were covered with debris in the stomach. Of the 9 patients, 8 had concomitant gastric ulcers, and the other patient had gastric lymphoma. Although a computed tomography (CT) scan was performed before the second-look endoscopy in 8 of the 9 patients, the bezoars were mistaken as food debris on CT findings and were overlooked in these patients. In conclusion, gastric bezoars may not be discovered during the initial esophagogastroduodenoscopy and CT scan. In cases with debris in the stomach, second-look endoscopy is essential to detect bezoars.

  2. Relaxation behavior and dose dependence of radiation induced radicals in irradiated mango

    International Nuclear Information System (INIS)

    Kameya, Hiromi; Kakita, Daisuke; Kaimori, Yoshihiko; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Shimoyama, Yuhei

    2010-01-01

    Mangoes are imported to Japan after treated with hot water. Recently, irradiated mangoes imported to U. S. are widely used. This paper reports on the ESR method for analyzing the radiation induced radicals of irradiated mangoes. Upon the γ ray irradiation, a strong single peak in the flesh and skin of mangoes was observed at g=2.004. This singlet peak may be attributed to organic free radicals. The ESR spectra of the flesh and skin of mangoes showed the radiation induced radicals due to cellulose by irradiation over 12 kGy. The relaxation times (T 1 and T 2 ) of the singlet signal were calculated. T 2 showed dose response according to increasing the irradiation dose levels, while T 1 was almost constant. The value of (T 1 T 2 ) 1/2 showed the dependence of irradiation dose level. (author)

  3. induced gastric acid secretion in the common african toad – bufo

    African Journals Online (AJOL)

    admin

    supported by the report of Sitmewoka (2000) which showed that absence of NO inhibits the secretion of gastric acid. However, Kato et al. (1998) observed that either exogenous or endogenous NO has inhibitory action on gastric acid secretion in mammals. This observation was supported by. Takeuchi et al. (1994) who also ...

  4. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  5. Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1

    OpenAIRE

    Lee, Min Ho; Cho, Yoonjung; Kim, Do Hyun; Woo, Hyun Jun; Yang, Ji Yeong; Kwon, Hye Jin; Yeon, Min Ji; Park, Min; Kim, Sa-Hyun; Moon, Cheol; Tharmalingam, Nagendran; Kim, Tae Ue; Kim, Jong-Bae

    2016-01-01

    Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucida...

  6. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au.

    Science.gov (United States)

    Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

    2016-05-28

    We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction.

  7. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: ...

  8. Effects on gastric mucosa induced by dental bleaching--an experimental study with 6% hydrogen peroxide in rats.

    Science.gov (United States)

    Paula, Anabela Baptista; Dias, Maria Isabel; Ferreira, Manuel Marques; Carrilho, Teresa; Marto, Carlos Miguel; Casalta, João; Cabrita, António Silvério; Carrilho, Eunice

    2015-10-01

    The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed. This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized.

  9. Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway.

    Science.gov (United States)

    Zhao, Zhongyan; Gong, Shilin; Wang, Shumin; Ma, Chunhua

    2015-09-01

    Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Lineshape theory of pigment-protein complexes: How the finite relaxation time of nuclei influences the exciton relaxation-induced lifetime broadening

    Energy Technology Data Exchange (ETDEWEB)

    Dinh, Thanh-Chung; Renger, Thomas, E-mail: thomas.renger@jku.at [Institut für Theoretische Physik, Johannes Kepler University Linz, Altenberger Str. 69, 4040 Linz (Austria)

    2016-07-21

    In pigment-protein complexes, often the excited states are partially delocalized and the exciton-vibrational coupling in the basis of delocalized states contains large diagonal and small off-diagonal elements. This inequality may be used to introduce potential energy surfaces (PESs) of exciton states and to treat the inter-PES coupling in Markov and secular approximations. The resulting lineshape function consists of a Lorentzian peak that is broadened by the finite lifetime of the exciton states caused by the inter-PES coupling and a vibrational sideband that results from the mutual displacement of the excitonic PESs with respect to that of the ground state. So far analytical expressions have been derived that relate the exciton relaxation-induced lifetime broadening to the Redfield [T. Renger and R. A. Marcus, J. Chem. Phys. 116, 9997 (2002)] or modified Redfield [M. Schröder, U. Kleinekathöfer, and M. Schreiber, J. Chem. Phys. 124, 084903 (2006)] rate constants of exciton relaxation, assuming that intra-PES nuclear relaxation is fast compared to inter-PES transfer. Here, we go beyond this approximation and provide an analytical expression, termed Non-equilibrium Modified Redfield (NeMoR) theory, for the lifetime broadening that takes into account the finite nuclear relaxation time. In an application of the theory to molecular dimers, we find that, for a widely used experimental spectral density of the exciton-vibrational coupling of pigment-protein complexes, the NeMoR spectrum at low-temperatures (T < 150 K) is better approximated by Redfield than by modified Redfield theory. At room temperature, the lifetime broadening obtained with Redfield theory underestimates the NeMoR broadening, whereas modified Redfield theory overestimates it by a similar amount. A fortuitous error compensation in Redfield theory is found to explain the good performance of this theory at low temperatures. Since steady state spectra of PPCs are often measured at low temperatures

  11. Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

    Directory of Open Access Journals (Sweden)

    Gündüz Miyase Gözde

    2017-09-01

    Full Text Available This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxyethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

  12. Thermomechanical Modeling of Laser-Induced Structural Relaxation and Deformation of Glass: Volume Changes in Fused Silica at High Temperatures [Thermo-mechanical modeling of laser-induced structural relaxation and deformation of SiO2 glass

    Energy Technology Data Exchange (ETDEWEB)

    Vignes, Ryan M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Soules, Thomas F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Stolken, James S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Settgast, Randolph R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Elhadj, Selim [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Matthews, Manyalibo J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). National Ignition Facility and Photon Sciences; Mauro, J.

    2012-12-17

    In a fully coupled thermomechanical model of the nanoscale deformation in amorphous SiO2 due to laser heating is presented. Direct measurement of the transient, nonuniform temperature profiles was used to first validate a nonlinear thermal transport model. Densification due to structural relaxation above the glass transition point was modeled using the Tool-Narayanaswamy (TN) formulation for the evolution of structural relaxation times and fictive temperature. TN relaxation parameters were derived from spatially resolved confocal Raman scattering measurements of Si–O–Si stretching mode frequencies. These thermal and microstructural data were used to simulate fictive temperatures which are shown to scale nearly linearly with density, consistent with previous measurements from Shelby et al. Volumetric relaxation coupled with thermal expansion occurring in the liquid-like and solid-like glassy states lead to residual stresses and permanent deformation which could be quantified. But, experimental surface deformation profiles between 1700 and 2000 K could only be reconciled with our simulation by assuming a roughly 2 × larger liquid thermal expansion for a-SiO2 with a temperature of maximum density ~150 K higher than previously estimated by Bruckner et al. Calculated stress fields agreed well with recent laser-induced critical fracture measurements, demonstrating accurate material response prediction under processing conditions of practical interest.

  13. Localized gastric amyloidosis differentiated histologically from scirrhous gastric cancer using endoscopic mucosal resection: a case report

    Directory of Open Access Journals (Sweden)

    Kamata Tsugumasa

    2012-08-01

    Full Text Available Abstract Introduction Amyloidosis most often manifests as a systemic involvement of multiple tissues and organs, and an amyloidal deposit confined to the stomach is extremely rare. It is sometimes difficult to provide a definitive diagnosis of localized gastric amyloidosis by biopsy specimen and diagnosis of amyloidosis in some cases has been finalized only after surgical resection of the stomach. Case presentation A 76-year-old Japanese woman with epigastric discomfort underwent an esophagogastroduodenoscopy procedure. The esophagogastroduodenoscopy revealed gastric wall thickening, suggesting scirrhous gastric carcinoma, at the greater curvature from the upper to the lower part of the gastric corpus. A biopsy specimen revealed amyloid deposits in the submucosal layer with no malignant findings. We resected a representative portion of the lesion by endoscopic mucosal resection using the strip biopsy method to obtain sufficient tissue specimens, and then conducted a detailed histological evaluation of the samples. The resected specimens revealed deposition of amyloidal materials in the gastric mucosa and submucosa without any malignant findings. Congo red staining results were positive for amyloidal protein and exhibited green birefringence under polarized light. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL amyloid protein type. Based on these results, gastric malignancy, systemic amyloidosis and amyloid deposits induced by inflammatory disease were excluded and this lesion was consequently diagnosed as localized gastric amyloidosis. Our patient was an older woman and there were no findings relative to an increase in gastrointestinal symptoms or anemia, so no further treatment was performed. She continued to be in good condition without any finding of disease progression six years after verification of our diagnosis. Conclusions We report an unusual case of primary amyloidosis of the stomach

  14. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

    Science.gov (United States)

    Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2015-08-03

    Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.

  15. Evidence for gastroprotective, anti-inflammatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats.

    Science.gov (United States)

    Hatware, Ketan Vinayakrao; Sharma, Sanjay; Patil, Kiran; Shete, Meghanath; Karri, Sravani; Gupta, Gaurav

    2018-07-01

    The Cordia dichotoma (CD) is having anticancer and other pharmacological effects as it contains mainly flavonoids. The present study was aimed to demonstrate the gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD revealed the presence of bioflavonoids and determination of quercetin was confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg, 100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally was used as the reference standard. The various parameters like gastric volume, gastric pH, total acidity, ulcer index, percent protection were estimated for assessment of anti-secretory and gastroprotective effects of MECD. At the same time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10 were also estimated according to their respective method of estimation using analyzing kit. The MECD have reduced gastric volume, total acidity and gastric mucosal damage in both the experimental models significantly and dose dependently as compared with control group. Similarly the antioxidant enzymes like SOD and CAT were increased while MDA levels were decreased significantly, at the same time TNF-α and IL-6 levels were decreased and anti-inflammatory IL-10 levels were increased significantly in MECD treated groups. Thus the pretreatment with MECD has shown significant gastroprotective potential probably due to its antioxidant and anti-inflammatory properties. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. [Molecular mechanisms of cytoprotective action of the plant proanthocyanidins in gastric lesions].

    Science.gov (United States)

    Zaiachkivs'ka, O S

    2006-01-01

    The molecular defence mechanisms against ethanol- and stress-induced (WRS) gastric lesions under the action of plant proanthocyanidins from grapefruit-seed extract (GSE) were investigated. Pre-treatment with GSE (8-64 mg/kg/day) in dose-dependent manner attenuated gastric lesions induced by 100% ethanol and WRS; the doses of GCE reducing these lesions by 50% (ID50) were 28 and 36 mg/kg/day, respectively and this protective effect was similar to that obtained with PGE2 analogue. Lesions reduction was also accompanied by improvement of gastric blood flow, antiradical action, increased mucosal generation of PGE2, antioxidant activity.

  17. Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.

    Science.gov (United States)

    Rattmann, Yanna D; Crestani, Sandra; Lapa, Fernanda R; Miguel, Obdúlio G; Marques, Maria C A; da Silva-Santos, J Eduardo; Santos, Adair R S

    2009-01-01

    Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.

  18. Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

    Directory of Open Access Journals (Sweden)

    Jung-Woo Kang

    2014-01-01

    Full Text Available Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101 on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-κB, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-κB translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators.

  19. Nuclear magnetic relaxation induced by exchange-mediated orientational randomization: longitudinal relaxation dispersion for a dipole-coupled spin-1/2 pair.

    Science.gov (United States)

    Chang, Zhiwei; Halle, Bertil

    2013-10-14

    In complex biological or colloidal samples, magnetic relaxation dispersion (MRD) experiments using the field-cycling technique can characterize molecular motions on time scales ranging from nanoseconds to microseconds, provided that a rigorous theory of nuclear spin relaxation is available. In gels, cross-linked proteins, and biological tissues, where an immobilized macromolecular component coexists with a mobile solvent phase, nuclear spins residing in solvent (or cosolvent) species relax predominantly via exchange-mediated orientational randomization (EMOR) of anisotropic nuclear (electric quadrupole or magnetic dipole) couplings. The physical or chemical exchange processes that dominate the MRD typically occur on a time scale of microseconds or longer, where the conventional perturbation theory of spin relaxation breaks down. There is thus a need for a more general relaxation theory. Such a theory, based on the stochastic Liouville equation (SLE) for the EMOR mechanism, is available for a single quadrupolar spin I = 1. Here, we present the corresponding theory for a dipole-coupled spin-1/2 pair. To our knowledge, this is the first treatment of dipolar MRD outside the motional-narrowing regime. Based on an analytical solution of the spatial part of the SLE, we show how the integral longitudinal relaxation rate can be computed efficiently. Both like and unlike spins, with selective or non-selective excitation, are treated. For the experimentally important dilute regime, where only a small fraction of the spin pairs are immobilized, we obtain simple analytical expressions for the auto-relaxation and cross-relaxation rates which generalize the well-known Solomon equations. These generalized results will be useful in biophysical studies, e.g., of intermittent protein dynamics. In addition, they represent a first step towards a rigorous theory of water (1)H relaxation in biological tissues, which is a prerequisite for unravelling the molecular basis of soft

  20. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au

    Science.gov (United States)

    Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

    2016-01-01

    We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction. PMID:28773549

  1. Gastric Necrosis due to Acute Massive Gastric Dilatation

    Directory of Open Access Journals (Sweden)

    Ibrahim Aydin

    2013-01-01

    Full Text Available 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.

  2. Gastric Necrosis due to Acute Massive Gastric Dilatation.

    Science.gov (United States)

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

    2013-01-01

    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.

  3. Acute effect of gamma irradiation on the gastric mucosa

    International Nuclear Information System (INIS)

    Dubois, A.; Dorval, E.D.; Rogers, J.E.; O'Connell, L.; Durakovic, A.; Conklin, J.J.

    1984-01-01

    The effect of gamma irradiation on the gastric mucosa has been studied in a primate model by evaluating endoscopically the rate of healing of gastric biopsies. Six male rhesus monkeys were subjected to fiberoptic gastroscopies performed under general anesthesia before and after total body exposure to Cobalt-60 (800 rads). Gastric biopsies were taken 3 hours and 2, 7, and 9 days after irradiation and examined using light microscopy. Gastric biopsies were found to heal in 3 days before irradiation; in contrast, they were still present 7 and 9 days after the biopsies in irradiated animals. Microscopic examination of the biopsies taken outside of the ulcer craters did not demonstrate any significant changes of the gastric surface epithelial cells. These data demonstrate that a gastric ulcer develops at the site of each endoscopic biopsy in irradiated monkeys whereas complete healing is observed in non-irradiated animals. The cause of this observation is unclear but it could be due to radiation induced suppression of the mitotic activity and of the cell renewal of gastric surface epithelial cells

  4. Enhanced relaxation of strained Ge{sub x}Si{sub 1-x} layers induced by Co/Ge{sub x}Si{sub 1-x} thermal reaction

    Energy Technology Data Exchange (ETDEWEB)

    Ridgway, M.C.; Elliman, R.G.; Rao, M.R. [Australian National Univ., Canberra, ACT (Australia); Baribeau, J.M. [National Research Council of Canada, Ottawa, ON (Canada)

    1993-12-31

    Enhanced relaxation of strained Ge{sub x}Si{sub l-x} layers during the formation of CoSi{sub 2} by Co/Ge{sub x}Si{sub 1-x} thermal reaction has been observed. Raman spectroscopy and transmission electron microscopy were used to monitor the extent of relaxation. Possible mechanisms responsible for the enhanced relaxation, including metal-induced dislocation nucleation, chemical and/or structural inhomogeneities at the reacted layer/Ge{sub x}Si{sub 1-x} interface and point defect injection due to silicide formation will be discussed. Also, methodologies for inhibiting relaxation will be presented. 11 refs., 1 fig.

  5. Enhanced relaxation of strained Ge{sub x}Si{sub 1-x} layers induced by Co/Ge{sub x}Si{sub 1-x} thermal reaction

    Energy Technology Data Exchange (ETDEWEB)

    Ridgway, M C; Elliman, R G; Rao, M R [Australian National Univ., Canberra, ACT (Australia); Baribeau, J M [National Research Council of Canada, Ottawa, ON (Canada)

    1994-12-31

    Enhanced relaxation of strained Ge{sub x}Si{sub l-x} layers during the formation of CoSi{sub 2} by Co/Ge{sub x}Si{sub 1-x} thermal reaction has been observed. Raman spectroscopy and transmission electron microscopy were used to monitor the extent of relaxation. Possible mechanisms responsible for the enhanced relaxation, including metal-induced dislocation nucleation, chemical and/or structural inhomogeneities at the reacted layer/Ge{sub x}Si{sub 1-x} interface and point defect injection due to silicide formation will be discussed. Also, methodologies for inhibiting relaxation will be presented. 11 refs., 1 fig.

  6. Gastric bypass surgery: Improving psoriasis through a GLP-1-dependent mechanism?

    DEFF Research Database (Denmark)

    Faurschou, Annesofie; Zachariae, Claus; Skov, Lone

    2011-01-01

    surgery. This most likely contributes importantly to the acute remission of type 2 diabetes, which is often induced by gastric bypass operations. The hormone is not hypersecreted after the purely restrictive bariatric procedure gastric banding and no case reports exist on improvement in psoriasis...... following gastric banding. Intriguingly, recent studies describe that GLP-1 may convey anti-inflammatory effects in addition to its effects on glucose homeostasis. Also, GLP-1 reduces appetite and gastrointestinal motility including gastric emptying, which reduces food intake and leads to weight loss. Thus...

  7. Sox2 Suppresses Gastric Tumorigenesis in Mice

    Directory of Open Access Journals (Sweden)

    Abby Sarkar

    2016-08-01

    Full Text Available Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. By using ChIP-seq analysis, we have found that the majority of Sox2 targets in gastric epithelial cells are tissue specific and related to functions such as endoderm development, Wnt signaling, and gastric cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem cell and epithelial self-renewal, yet Sox2+ cells are highly susceptible to tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances, rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, providing a mechanistic basis for the observed phenotype. Together, these data identify Sox2 as a context-dependent tumor suppressor protein that is dispensable for normal tissue regeneration but restrains stomach adenoma formation through modulation of Wnt-responsive and intestinal genes.

  8. Hyperfine relaxation of an optically pumped cesium vapor

    International Nuclear Information System (INIS)

    Tornos, J.; Amare, J.C.

    1986-01-01

    The relaxation of hyperfine orientation indirectly induced by optical pumping with a σ-polarized D 1 -light in a cesium vapor in the presence of Ar is experimentally studied. The detection technique ensures the absence of quadrupole relaxation contributions in the relaxation signals. The results from the dependences of the hyperfine relaxation rate on the temperature and argon pressure are: diffusion coefficient of Cs in Ar, D 0 = 0.101 +- 0.010 cm 2 s -1 at 0 0 C and 760 Torr; relaxation cross section by Cs-Ar collisions, σ/sub c/ = (104 +- 5) x 10 -23 cm 2 ; relaxation cross section by Cs-Cs (spin exchange) collisions, σ/sub e//sub x/ = (1.63 +- 0.13) x 10 -14 cm 2

  9. THE EFFECT OF ALOE VERA ON GASTRIC ACID SECRETION ...

    African Journals Online (AJOL)

    The effect of varying doses of ethanol extract of Aloe vera (Liliaceae) on acute gastric mucosal lesions induced by 0.6M HCl and acid output was studied in the pylorus ligated and lumen perfuse rats respectively. Acid secretion was determined by titration of the collected gastric juice to pH 7.0. Intraperitoneal injection of Aloe ...

  10. F-center mechanism of long-term relaxation in lead zirconate-titanate-based piezoelectric ceramics. 1. After-heating relaxation

    Directory of Open Access Journals (Sweden)

    V. M. Ishchuk

    2015-12-01

    The oxygen vacancies-based model for description of the long-time relaxation processes is suggested. The model takes into account oxygen vacancies on the sample’s surface ends, their conversion into F+- and F0-centers under external effects (due to the liberation of the pyroelectric charge and subsequent relaxation of these centers into the simple oxygen vacancies after the actions termination. The initial sample’s state is electroneutrality one. F-center formation leads to the violation of the original sample’s electroneutrality, and generates DC electric field into the sample. Relaxation of F-centers is accompanied by decreasing of electric field, induced by them, and dielectric constant relaxation as consequent effect.

  11. How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

    Science.gov (United States)

    Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

    2016-09-01

    The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

  12. Hedgehog Signaling Regulates the Survival of Gastric Cancer Cells by Regulating the Expression of Bcl-2

    Science.gov (United States)

    Han, Myoung-Eun; Lee, Young-Suk; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae-Ock

    2009-01-01

    Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. PMID:19742123

  13. Gastric emptying in patients with chronic fatigue syndrome

    International Nuclear Information System (INIS)

    Sand, A.; Hulstaert, J.; Wanet, P.; Uyttersprot, A.; Meirleir, K. de

    2002-01-01

    Chronic fatigue syndrome (CFS) is a debilitating chronic illness of unknown cause characterized by mental fatigue and sensorimotor disturbances. Moreover, gastrointestinal symptoms (GI) are frequently noticed in those patients. A possible cause could be a dysfunction of the NANC neurotransmitter system in which Vasoactive Intestinal Polypeptide and NO plays an important role in the speed of the gastric relaxation. The Aim of this study was to determine the prevalence of gastric motility disorder in CFS patients. Materials and Methods: 51 patients affected by CFS (45 females and 6 males; mean age 38.5 ± 14.7 y) were prospectively studied by a gastric emptying scintigraphy and the results compared with a control population. The patients were categorized in two clinical groups according to the severity criteria of Holmes and Fukuda (H/F - or H/F +). The presence of GI symptoms was noticed for each patient. Gastric emptying was assessed by the standard procedure according to the guidelines of the Belgian Society of Nuclear Medicine. The acquisition of a series of 10 static images in anterior and posterior projections was started after a test meal (1 fried egg + 20 Mbq Tc99m sulfur colloids, 2 pieces of bread and 125 ml of water). Geometric means were calculated after correction for the half-life of Tc99m and the gastric half-emptying time (T1/2) was determined for each patient. Results: A significantly prolonged T 1/2 was found in CFS patients (97.8 ± 41.6 min) compared to our control population (70 ± 15 min) independently of the presence of associated GI symptoms. (p<0.01) There was also a close relationship between the T1/2 and severity of the CFS disease: the gastric emptying time of the two CFS groups (according to the H/F criteria) were respectively 78.9 and 112.9 min. which is highly significant. (p<0.05). Conclusion: We conclude that delayed gastric emptying is frequently encountered in patients with CFS (with mild or severe symptoms of gastroparesis) which

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

    Science.gov (United States)

    Eamlamnam, Kallaya; Patumraj, Suthiluk; Visedopas, Naruemon; Thong-Ngam, Duangporn

    2006-04-07

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

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

    Institute of Scientific and Technical Information of China (English)

    Kallaya Eamlamnam; Suthiluk Patumraj; Naruemon Visedopas; Duangporn Thong-Ngam

    2006-01-01

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

  16. Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases

    International Nuclear Information System (INIS)

    Ishiwatari, Takao; Yamamoto, Yoshiro; Nakayama, Haruo; Shibuya, Kazutoshi; Okubo, Yoichiro; Tochigi, Naobumi; Wakayama, Megumi; Nemoto, Tetsuo; Kobayashi, Junko; Shinozaki, Minoru; Aki, Kyoko; Sasai, Daisuke

    2014-01-01

    Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial

  17. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin

    DEFF Research Database (Denmark)

    Egerod, Kristoffer Lihme; Engelstoft, Maja Storm; Grunddal, Kaare Villum

    2012-01-01

    Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing...... enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive...... to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity....

  18. Effect of nifedipine on gastric emptying in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Traube, M.; Lange, R.C.; McAllister, R.G.; McCallum, R.W.

    1985-05-01

    Nifedipine (N) inhibits calcium entry into smooth muscle cells and relaxes esophageal smooth muscle. The authors studied N's effect on gastric emptying of liquids and solids. Ten normal subjects underwent radionuclide (In-111-DTPA in water and Tc-99m-sulfur colloid tagged to chicken liver) emptying tests with and without 30 mg N given orally 20 min prior to meal ingestion. Peak plasma N levels were either 30 or 60 min after drug dosing and showed a 3-fold variation (low 145 ng/ml, high 434 ng/ml). Both mean N levels and integral concentration time values were twice as high as those obtained after 30 mg sublingual dosing in normals previously studied in our lab. The authors conclude that plasma N levels which are associated with significant esophageal motility effects do not change gastric emptying in normal subjects. The data also show that N levels are greater after oral than sublingual dosing of 30 mg in normal subjects.

  19. Effect of nifedipine on gastric emptying in normal subjects

    International Nuclear Information System (INIS)

    Traube, M.; Lange, R.C.; McAllister, R.G.; McCallum, R.W.

    1985-01-01

    Nifedipine (N) inhibits calcium entry into smooth muscle cells and relaxes esophageal smooth muscle. The authors studied N's effect on gastric emptying of liquids and solids. Ten normal subjects underwent radionuclide (In-111-DTPA in water and Tc-99m-sulfur colloid tagged to chicken liver) emptying tests with and without 30 mg N given orally 20 min prior to meal ingestion. Peak plasma N levels were either 30 or 60 min after drug dosing and showed a 3-fold variation (low 145 ng/ml, high 434 ng/ml). Both mean N levels and integral concentration time values were twice as high as those obtained after 30 mg sublingual dosing in normals previously studied in our lab. The authors conclude that plasma N levels which are associated with significant esophageal motility effects do not change gastric emptying in normal subjects. The data also show that N levels are greater after oral than sublingual dosing of 30 mg in normal subjects

  20. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    Science.gov (United States)

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  1. Effects on gastric mucosa induced by dental bleaching – an experimental study with 6% hydrogen peroxide in rats

    Science.gov (United States)

    PAULA, Anabela Baptista; DIAS, Maria Isabel; FERREIRA, Manuel Marques; CARRILHO, Teresa; MARTO, Carlos Miguel; CASALTA, João; CABRITA, António Silvério; CARRILHO, Eunice

    2015-01-01

    The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed. Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized. PMID:26537721

  2. Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

    Directory of Open Access Journals (Sweden)

    E.F. Collares

    2017-08-01

    Full Text Available Atropine (AT and dipyrone (Dp induce a delay of gastric emptying (GE of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group. Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg. Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg displayed significantly lower %GR compared to its control (vehicle-treated group, which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

  3. Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues.

    Science.gov (United States)

    Cheng, Xiao Jiao; Lin, Jia Cheng; Ding, Yan Fei; Zhu, Liming; Ye, Jing; Tu, Shui Ping

    2016-02-09

    Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious pathological changes were observed in organs (e.g. heart, liver, lung and kidney) in YM155-treated mice. Our results demonstrated that YM155 inhibits cell proliferation, induces cell apoptosis, reduces cancer stem cell expansion, and inhibits xenograft tumor growth in gastric cancer cells. Our results elucidate a new mechanism by which YM155 inhibits gastric cancer growth by inhibition of CSCs. YM155 may be a promising agent for gastric cancer treatment.

  4. Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

    Directory of Open Access Journals (Sweden)

    Yi Ting

    2012-11-01

    Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

  5. Thermally-induced electronic relaxation in structurally-modified Cu0.1Ni0.8Co0.2Mn1.9O4 spinel ceramics

    International Nuclear Information System (INIS)

    Shpotyuk, O.; Balitska, V.; Brunner, M.; Hadzaman, I.; Klym, H.

    2015-01-01

    Thermally-induced electronic relaxation in structurally-modified Cu 0.1 Ni 0.8 Co 0.2 Mn 1.9 O 4 spinel ceramics is shown to be adequately described by stretched exponential function on time. This kinetics is defined by microsctructure perfectness of the relaxing media, showing obvious onset to stretched exponential behaviour with non-exponentionality index attaining close to 0.43 values for high-monolith ceramics and smaller ones in fine-grained ceramics. Percolation threshold in relaxation-degradation kinetics is detected for ceramics with 10% of NiO extractions, showing the smallest but most prolonged single-path degradation effect. This finding is treated in terms of Phillips’ axiomatic diffusion-to-trap model, where only one of two relaxation channels (caused by operative short-range forces) occurs to be effective, while additional non-operative channels contribute to electronic relaxation in fine-grained ceramics

  6. The relaxant effect induced by Allium sativum L. bulb aqueous extract on rat isolated trachea

    Science.gov (United States)

    Fehri, Badreddine; Ahmed, Mueen K.K.; Aiache, Jean-Marc

    2011-01-01

    Background: Garlic plays an important role in complementary and alternative medicine. Most people believe in and use herbal products even when they have not been as thoroughly researched as garlic. Garlic is also known for its beneficial effects on the cardiovascular system. Materials and Methods: The relaxant effect of Allium sativum L. bulb aqueous extract (ASBAE) containing 0.06%-0.10% of allicin was studied on isolated smooth muscle of trachea of rats precontracted using acetylcholine (10−5 M). Results: It was found that ASBAE induced a dose-dependent relaxation with recorded EC 50 values of 71.87 ± 5.90 µg/mL (n = 7). Pretreatments with mepyramine (10−7 M), methysergide (10−7 M), caffeine (10−6 M), theophylline (10−6 M), nifedipine (10−6 M), and dipyridamole (10−6 M) did not alter ASBAE concentration-response curves. In turn, concentration-response curves to ASBAE were significantly shifted toward right in the presence of aspirin (3.10−3 M), indomethacin (10−6 M), prazosin (10−6 M), and propranolol (10−7 M). Conclusion: It is suggested that the recorded relaxation results are due to the release of prostaglandins E 1 and E 2 consecutively to α- and β-adrenoreceptor stimulation. PMID:21472073

  7. Sup(1)H n.m.r. relaxation of radiation induced crosslinking in polyester-styrene systems

    International Nuclear Information System (INIS)

    Andreis, M.; Veksli, Z.; Ranogajec, F.; Hedvig, P.

    1989-01-01

    The structure and dynamics of a network formed by radiation induced crosslinking of polyesters based on 1,6-hexane diol and 1,2-propylene glycol and maleic anhydride (HDF and PGF, respectively) with styrene is studied by proton pulsed n.m.r. spectroscopy. The dependence of spin-lattice, T 1 , and spin-spin, T 2 , relaxation times on the structure of polyester chain, molar ratios of styrene to polyester unsaturations and the radiation doses are analysed in terms of network formation and structure, and their effect on molecular motion. Above the gel point, at temperatures above the glass transition, the presence of two T 2 components reflects the heterogeneity of the network structure in both resins. Parallel with the n.m.r. relaxation measurements the crosslink density was determined from the extracted gel phase or double bonds (fumaric and styrene) participating in the crosslinking process. (author)

  8. Spin-orbit coupling induced two-electron relaxation in silicon donor pairs

    Science.gov (United States)

    Song, Yang; Das Sarma, S.

    2017-09-01

    We unravel theoretically a key intrinsic relaxation mechanism among the low-lying singlet and triplet donor-pair states in silicon, an important element in the fast-developing field of spintronics and quantum computation. Despite the perceived weak spin-orbit coupling (SOC) in Si, we find that our discovered relaxation mechanism, combined with the electron-phonon and interdonor interactions, drives the transitions in the two-electron states over a large range of donor coupling regimes. The scaling of the relaxation rate with interdonor exchange interaction J goes from J5 to J4 at the low to high temperature limits. Our analytical study draws on the symmetry analysis over combined band, donor envelope, and valley configurations. It uncovers naturally the dependence on the donor-alignment direction and triplet spin orientation, and especially on the dominant SOC source from donor impurities. While a magnetic field is not necessary for this relaxation, unlike in the single-donor spin relaxation, we discuss the crossover behavior with increasing Zeeman energy in order to facilitate comparison with experiments.

  9. Gastric cancer associated with refractory cytomegalovirus gastritis.

    Science.gov (United States)

    Ueno, Masayuki; Shimodate, Yuichi; Yamamoto, Shumpei; Yamamoto, Hiroshi; Mizuno, Motowo

    2017-12-01

    Cytomegalovirus (CMV) sometimes causes gastritis, especially in immunocompromised patients, but whether CMV gastritis promotes the development of gastric cancer is unknown. Here, we report a case of gastric cancer that developed in the presence of CMV gastritis, which had been present for at least 4 years and was refractory to treatment. An 80-year-old woman had noted epigastric discomfort and appetite loss. Esophagogastroduodenoscopy revealed a shallow geographical ulcer extending from the upper body to the pylorus. Histological findings of the biopsy and serology were suggestive of CMV gastritis. Serum anti-Helicobacter pylori antibody test was positive, suggesting co-infection with CMV and H. pylori. Her gastritis was unimproved with repeated antiviral therapy and eradication of H. pylori. Thirty months later, wide-spread gastric cancer had developed. We suggest the possibility that the addition of chronic inflammation of CMV infection to H. pylori-induced gastritis facilitated the development of gastric cancer.

  10. Relaxation in x-space magnetic particle imaging.

    Science.gov (United States)

    Croft, Laura R; Goodwill, Patrick W; Conolly, Steven M

    2012-12-01

    Magnetic particle imaging (MPI) is a new imaging modality that noninvasively images the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIOs). MPI has demonstrated high contrast and zero attenuation with depth, and MPI promises superior safety compared to current angiography methods, X-ray, computed tomography, and magnetic resonance imaging angiography. Nanoparticle relaxation can delay the SPIO magnetization, and in this work we investigate the open problem of the role relaxation plays in MPI scanning and its effect on the image. We begin by amending the x-space theory of MPI to include nanoparticle relaxation effects. We then validate the amended theory with experiments from a Berkeley x-space relaxometer and a Berkeley x-space projection MPI scanner. Our theory and experimental data indicate that relaxation reduces SNR and asymmetrically blurs the image in the scanning direction. While relaxation effects can have deleterious effects on the MPI scan, we show theoretically and experimentally that x-space reconstruction remains robust in the presence of relaxation. Furthermore, the role of relaxation in x-space theory provides guidance as we develop methods to minimize relaxation-induced blurring. This will be an important future area of research for the MPI community.

  11. The Impact of Heller Myotomy on Integrated Relaxation Pressure in Esophageal Achalasia.

    Science.gov (United States)

    Salvador, Renato; Savarino, Edoardo; Pesenti, Elisa; Spadotto, Lorenzo; Capovilla, Giovanni; Cavallin, Francesco; Galeazzi, Francesca; Nicoletti, Loredana; Merigliano, Stefano; Costantini, Mario

    2016-01-01

    A new high-resolution manometry (HRM) parameter, the integrated relaxation pressure (IRP), has been proposed for the assessment of esophageal-gastric junction (EGJ) relaxation. Our aim was to assess the effect of Heller myotomy on IRP in achalasia patients. We prospectively collected data on achalasia patients who underwent HRM between 2009-2014. Barium swallow was used to assess esophageal diameter and shape. Manometric diagnoses were performed by using the Chicago Classification v3. All patients with a confirmed diagnosis of achalasia were treated surgically with Heller Myotomy One hundred thirty-nine consecutive achalasia patients (M:F = 72:67) represented the study population. All the patients had 100% simultaneous waves but 11 had an IRP achalasia, and how it changes after surgical treatment. An increased preoperative IRP correlated directly with a more severe dysphagia. The IRP was restored to normal by Heller myotomy.

  12. Models for multiple relaxation processes in collagen fiber

    Indian Academy of Sciences (India)

    ... originate from stress strain induced changes in hydrogen bond network whereas the other seems to be more strongly coupled to salt like bridges and electrostatic interactions. Urea alters the activation energy for one relaxation step while pH and solvent dielectric constant alter the relaxation behavior one set of processes.

  13. Influence of thyroid states on stress gastric ulcer formation

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, D.E.; Walker, C.H.; Mason, G.A.

    1988-01-01

    This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-resistant stress. Normal (euthyroid), hyperthyroid and hypothyroid rats were used. Gastric lesion incidence and severity was significantly increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T/sub 4/) were significantly elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine, but not T/sub 4/ 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of /sup 3/H-dihydroalprenolol to ..beta..-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increase rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism for this response may involve decreased brain nonadrenergic receptor function.

  14. Influence of thyroid states on stress gastric ulcer formation

    International Nuclear Information System (INIS)

    Hernandez, D.E.; Walker, C.H.; Mason, G.A.

    1988-01-01

    This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-resistant stress. Normal (euthyroid), hyperthyroid and hypothyroid rats were used. Gastric lesion incidence and severity was significantly increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T 4 ) were significantly elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine, but not T 4 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of 3 H-dihydroalprenolol to β-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increase rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism for this response may involve decreased brain nonadrenergic receptor function

  15. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats.

    Science.gov (United States)

    Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Al Batran, Rami; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

    2015-01-01

    Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.

  16. Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

    Directory of Open Access Journals (Sweden)

    E.F. Collares

    2005-01-01

    Full Text Available Dipyrone administered intravenously (iv or intracerebroventricularly (icv delays gastric emptying (GE in rats. Gamma-aminobutyric acid (GABA is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ or 80 mg/kg (240 µmol/kg dipyrone (Dp iv, followed by icv injection of 10 µl vehicle (bac0, or 0.5 (bac0.5, 1 (bac1 or 2 µg (bac2 baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (Cicv or an equal volume of a solution containing 4 µmol (1333.2 µg dipyrone (Dp icv, followed by 5 µl vehicle (bac0 or 1 µg baclofen (bac1. GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%. Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%. The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors.

  17. How to stomach an epigenetic insult: the gastric cancer epigenome.

    Science.gov (United States)

    Padmanabhan, Nisha; Ushijima, Toshikazu; Tan, Patrick

    2017-08-01

    Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies. Studies have identified different subgroups of gastric cancer displaying not just genetic, but also distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic abnormalities in gastric cancer are not mere bystander events, but rather promote carcinogenesis through active mechanisms. Epigenetic aberrations, induced by pathogens such as Helicobacter pylori, are an early component of gastric carcinogenesis, probably preceding genetic abnormalities. This Review summarizes our current understanding of the gastric cancer epigenome, highlighting key advances in recent years in both tumours and pre-malignant lesions, made possible through targeted and genome-wide technologies. We focus on studies related to DNA methylation and histone modifications, linking these findings to potential therapeutic opportunities. Lessons learned from the gastric cancer epigenome might also prove relevant for other gastrointestinal cancers.

  18. Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats.

    Science.gov (United States)

    Szasz, Theodora; Watts, Stephanie W

    2010-06-01

    Uric acid (UA) results from xanthine oxidase (XO) catabolism of xanthine and is the final product of purine catabolism in humans. In this species, hyperuricemia is associated with gout, nephropathy, and increased cardiovascular disease risk. Although the effects of hyperuricemia in vascular biology are overall controversial, UA has been described as an antioxidant and as potentially improving endothelial function. Hypertension is associated with endothelial dysfunction. We hypothesized that UA improves the endothelial function of aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. UA (100 microM) in the presence of the uricase inhibitor oxonic acid (10 microM) did not modify relaxation to acetylcholine (ACh) (1 nM-10 microM) in the aorta from nontreated, sham normotensive, and DOCA-salt hypertensive rats [response to 10 microM ACh for UA versus vehicle, respectively: nontreated = 37 +/- 7 versus 48 +/- 7%, sham = 53 +/- 15 versus 57 +/- 20%, DOCA = 81 +/- 4 versus 85 +/- 2% from 20 microM prostaglandin 2alpha (PGF(2alpha))-induced contraction]. Allopurinol (100 microM), a XO inhibitor, did not significantly alter the ACh-induced relaxation of sham and DOCA aortic rings (response to 10 microM ACh for allopurinol versus vehicle, respectively: sham = 61 +/- 5 versus 68 +/- 9%, DOCA = 87 +/- 6 versus 88 +/- 3% from 20 microM PGF(2alpha)-induced contraction). Uricemia, ranging from unmeasurable to 547 microM in sham and to 506 microM in DOCA rats, was not significantly different between these two groups. The expression and activity of XO, as well as the expression of uricase, were not different between sham and DOCA rat aorta. We conclude that, at least in vitro, UA does not affect the ACh-induced relaxation of normotensive and DOCA-salt hypertensive rats.

  19. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans....... METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  20. The Physiology and pathophysiology of laparoscopic adjustable gastric bands

    OpenAIRE

    Burton, Paul Robert

    2017-01-01

    The laparoscopic adjustable gastric band (LAGB) has rapidly emerged as one of the most powerful medical interventions available. Originally a physically restrictive operation, evolution of the technique has resulted in what is now hypothesised to be a satiety inducing procedure. There is limited understanding of associated physiological processes; including oesophageal motility, transit and gastric emptying. Intraluminal pressure effects of the LAGB have not been identified. Recently, a ...

  1. Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

    Science.gov (United States)

    Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

    2017-04-01

    Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

  2. GRAIN ALIGNMENT INDUCED BY RADIATIVE TORQUES: EFFECTS OF INTERNAL RELAXATION OF ENERGY AND COMPLEX RADIATION FIELD

    International Nuclear Information System (INIS)

    Hoang, Thiem; Lazarian, A.

    2009-01-01

    Earlier studies of grain alignment dealt mostly with interstellar grains that have strong internal relaxation of energy which aligns the grain axis of maximum moment of inertia (the axis of major inertia) with respect to the grain's angular momentum. In this paper, we study the alignment by radiative torques for large irregular grains, e.g., grains in accretion disks, for which internal relaxation is subdominant. We use both numerical calculations and the analytical model of a helical grain introduced by us earlier. We demonstrate that grains in such a regime exhibit more complex dynamics. In particular, if initially the grain axis of major inertia makes a small angle with angular momentum, then radiative torques can align the grain axis of major inertia with angular momentum, and both the axis of major inertia and angular momentum are aligned with the magnetic field when attractors with high angular momentum (high-J attractors) are available. For alignment without high-J attractors, beside the earlier studied attractors with low angular momentum (low-J attractors), there appear new low-J attractors. In addition, we also study the alignment of grains in the presence of strong internal relaxation, but induced not by a radiation beam as in earlier studies but instead induced by a complex radiation field that can be decomposed into dipole and quadrupole components. We found that in this situation the parameter space q max , for which high-J attractors exist in trajectory maps, is more extended, resulting in the higher degree of polarization expected. Our results are useful for modeling polarization arising from aligned dust grains in molecular clouds.

  3. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

    Science.gov (United States)

    da Silva, Luisa Mota; Allemand, Alexandra; Mendes, Daniel Augusto G B; Dos Santos, Ana Cristina; André, Eunice; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Dartora, Nessana; Marques, Maria Consuelo Andrade; Baggio, Cristiane Hatsuko; Werner, Maria Fernanda

    2013-01-01

    We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.

    Science.gov (United States)

    Uchida, Masayuki; Kobayashi, Orie; Shimizu, Kimiko

    2017-01-01

    Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1- 13 C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

  5. Comparative healing property of kombucha tea and black tea against indomethacin-induced gastric ulceration in mice: possible mechanism of action.

    Science.gov (United States)

    Banerjee, Debashish; Hassarajani, Sham A; Maity, Biswanath; Narayan, Geetha; Bandyopadhyay, Sandip K; Chattopadhyay, Subrata

    2010-12-01

    The healing activity of black tea (BT) and BT fermented with Candida parapsilosis and kombucha culture, designated as CT and KT respectively against the indomethacin-induced stomach ulceration has been studied in a mouse model. The KT sample (KT4) produced by fermenting BT for four days, showed the best DPPH radical scavenging capacity and phenolics contents. Hence the ulcer-healing activity of KT4 was compared with those of CT4 and BT. All the tea extracts (15 mg kg(-1)) could effectively heal the gastric ulceration as revealed from the histopathological and biochemical studies, with relative efficacy as KT4 > CT4 ∼ BT. The healing capacities of the tea extracts could be attributed to their antioxidant activity as well as the ability to protect the mucin content of the gastric tissues. In addition, the ability of KT4 to reduce gastric acid secretion might also contribute to its ulcer-healing activity. The tea preparation KT4 (15 mg kg(-1)) was as effective as the positive control, omeprazole (3 mg kg(-1)) in ulcer healing.

  6. Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism.

    Science.gov (United States)

    Cheah, Esther Y; Burcham, Philip C; Mann, Tracy S; Henry, Peter J

    2014-05-01

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE₂ was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK₁ receptor antagonist RP-67580, and the EP₂ receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE₂ release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK₁ receptor-expressing epithelial cells, and EP₂-receptor expressing airway smooth muscle cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The relaxation phenomena of radicals induced in irradiated fresh mangoes

    International Nuclear Information System (INIS)

    Kikuchi, Masahiro; Morishita, Norio; Kobayashi, Yasuhiko; Ogawa, Hideyuki; Shimoyama, Yuhei; Ukai, Mitsuko

    2009-01-01

    Using the γ-irradiated fresh mangoes followed by freeze-drying and powderization, electron spin resonance spectrometry of specimens was performed. As a result, a strong single peak in the flesh, the pericarp and the seed was observed at g=2.004 and attributed to organic free radicals. When relaxation times of the peak was calculated using the method of Lund et al., T 2 showed dose responses according to increasing doses while T 1 was almost constant. Dose responsibility of the relaxation time T 2 obtained from flesh specimens of the mangoes could be measured regardless of the preservation period of 1 to 9 days following γ-irradiation. Therefore, there might be possible to detect the irradiation treatment of fresh mangoes using relaxation time T 2 . (author)

  8. Bovine alpha-lactalbumin stimulates mucus metabolism in gastric mucosa.

    Science.gov (United States)

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

    2007-02-01

    Bovine alpha-lactalbumin (alpha-LA), a major milk protein, exerts strong gastroprotective activity against rat experimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of alpha-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were selected for observation of the direct activity of alpha-LA on gastric mucosal cells and cultured in the presence of either alpha-LA or ovalbumin (OVA), a reference protein showing no gastroprotective activity. Amounts of synthesized and secreted mucin, a major component of mucus, were determined using [3H]glucosamine as a tracer, and prostaglandin E2 (PGE2) levels in the culture medium were determined by RIA. For the in vivo study, the thickness of the mucus gel layer, a protective barrier for gastric mucosa, was evaluated histochemically in rat gastric mucosa. alpha-Lactalbumin (3 mg/mL) significantly stimulated mucin synthesis and secretion in RGM1 cells and also increased PGE2 levels in the culture medium. In contrast, OVA showed no enhancing effects u