Wyniki wyszukiwania

1

Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins

100%

Brzozowski T., Konturek P. C., Pajdo R., Ptak-Belowska A., Kwiecien S., Pawlik M., Drozdowicz D., Sliwowski Z., Brzozowski B., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 2

Prostaglandins mediate various physiological aspects of mucosal defense and the suppression of prostaglandin synthesis in the stomach is a critical event in terms of the development of mucosal injury after NSAID administration. However, it has become clear that other mediators besides prostaglandins can similarly act to protect the stomach from injury. For instance, nitric oxide (NO) released from vascular epithelium, epithelial cells of gastrointestinal tract and sensory nerves can influence many of the same components of mucosal defense as do prostaglandins. Thus, administration of NO in a form of NO-donors exert protective influence on the stomach from the injury that usually occurs when mucosal prostaglandin levels are suppressed. The new class of NO releasing NSAIDs, including NO-aspirin, represent a very promising approach to reducing the toxicity of anti-inflammatory drugs. Lipoxins are another group of lipid mediators that can protect the stomach. Aspirin-triggered lipoxin synthesis, via COX-2, acts to reduce the severity of damage induced by this drug. Lipoxin analogues may prove to be useful for preventing mucosal injury and for modulating mucosal inflammation. Aspirin-triggered lipoxin also seems to play in important role in gastric adaptation during chronic aspirin administration. Suppression of COX-2 activity by selective COX-2 inhibitors abolishes the production of this endogenous gastroprotective substance and diminishes the gastric tolerability of NSAIDS and gastric adaptation to these drugs. This review was designed to give an updated overview on the physiological factors and experimental and clinical attempts that were used or may be used in the future as the therapeutic approach to counteract adverse effects in the stomach associated with NSAID ingestion.

2

Helicobacter pylori and gastric adaptation to repeated aspirin administration in humans

86%

Konturek J. W., Dembinski A., Konturek S. J., Domschke W.

Journal of Physiology and Pharmacology. Supplement

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1997

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tom 48

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nr 1

3

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Heat shock protein 70 (HSP70) in gastric adaptation to aspirin in Helicobacter pylori infection

86%

Konturek J. W., Fischer H., Konturek P. C., Huber V., Boknik P., Luess H., Neumann J., Brzozowski T., Schmitz W., Hahn E. G., Domschke W., Konturek S. J.

Journal of Physiology and Pharmacology

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2001

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tom 52

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nr 1

4

Role of prostaglandins, sensory nerves, nitric oxide and growth factors in gastric adaptation to topical irritants

72%

Konturek S. J., Brzozowski T., Konturek J. W., Domschke W.

Journal of Physiology and Pharmacology. Supplement

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1993

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tom 44

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nr 2

5

Role of prostaglandins in gastroprotection and gastric adaptation

58%

Brzozowski T., Konturek P. C., Konturek S. J., Brzozowska I., Pawlik T.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 5

33-55

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenaxe (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hiperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE2 or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhamcement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE2 generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

6

Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals

58%

Brzozowski T., Konturek P. C., Sliwowski Z., Kwiecien S., Drozdowicz D., Pawlik M., Mach K., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 3

67-79

Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drugs (NSAID) are major pathogenic factors in peptic ulcer disease but whether these two factors exert synergistic or antagonistic action on the gastric mucosa has been a subject of controversy. The classic concept states that there is an increased ulcer occurrence and bleeding in patients with both H. pylori infection and NSAID use. However, the question whether the H. pylori eradication therapy in NSAID users reduces the occurrence of peptic ulcer has not been fully addressed. Studies on secondary prevention of NSAID-associated ulcers in H. pylori patients have indicated that H. pylori eradication results in impaired ulcer healing with an effect on the rate of peptic ulcer occurrence. On the other hand, the treatment of H. pylori in patients with no prior history of chronic NSAID therapy has been shown to decrease the risk of peptic ulcer. Studies in experimental animals revealed for instance, that the H. pylori infection augments the gastric mucosal damage induced by NSAID in Mongolian gerbils. In rats with preexisting chromic gastric ulcers, H. pylori infection attenuated significantly the aspirin-induced inhibition of ulcer healing and accompanying fall in the gastric blood flow at the margin of these ulcers, suggesting negative interaction between aspirin and H. pylori on ulcerogenesis. Accumulated evidence in humans and animals shows that both aspirin and H. pylori upregulate the expression of cyclooxygenase (COX)-2 both at mRNA and protein levels at the ulcer margin, but failed to influence significantly that of COX-1. It was, therefore, proposed that H. pylori may in fact, antagonize, aspirin-induced delay of ulcer healing due to suppression of acid secretion by the enhancement in PGE2 possibly derived from COX-2 expression and activity and to the overexpression of growth factors such as TGFalpha and VEGF. The present review summarizes and further addresses the issue of the interaction between these two major ulcer risk factors determined in the stomach of humans and experimental animals.

7

Helicobacter pylori and gastric adaptation to repeated aspirin administration in humans

58%

Konturek J. W., Dembinski A., Konturek S. J., Domschke W.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 3

8

Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H.pylori - derived gastrotoxins

44%

Konturek P. C.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 1

Ograniczanie wyników

Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins

Helicobacter pylori and gastric adaptation to repeated aspirin administration in humans

Heat shock protein 70 (HSP70) in gastric adaptation to aspirin in Helicobacter pylori infection

Role of prostaglandins, sensory nerves, nitric oxide and growth factors in gastric adaptation to topical irritants

Role of prostaglandins in gastroprotection and gastric adaptation

Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals

Helicobacter pylori and gastric adaptation to repeated aspirin administration in humans

Physiological, immunohistochemical and molecular aspects of gastric adaptation to stress, aspirin and to H.pylori - derived gastrotoxins