Wyniki wyszukiwania

1

Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man

100%

Dajani E. Z., Islam K.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 2

It is well established that the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) increase the vulnerability of the gastrointestinal (GI) mucosa for the development of peptic lesions and serious ulcer complications. In addition, selective and traditional NSAIDs have also been associated with increased frequency of cardiovascular toxicity, especially in susceptible patients. The objective of this communication is to provide an overview of the salient GI and cardiovascular (CV) toxicity for these drugs. Traditional NSAIDs inhibit the constitutional cyclooxygenase-1 (COX-1) enzyme responsible for eicosanoids biosynthesis not only in joints, a beneficial effect, but also in the stomach, a detrimental effect. Selective NSAIDs were specifically designed to preferentially inhibit the cyclooxygenase-2 (COX-2), an inducible enzyme mediating the production of inflammatory eicosanoids in the joints but sparing the endogenous protective eicosanoids in the stomach. Selective COX-2 inhibitors (COXIBs) have been shown to possess much improved GI tolerability and reduced GI related adverse events when compared with nonselective COX-1inhibitors. An unexpected CV toxicity had emerged during the COXIBs post marketing outcome studies. Many subsequent studies were carried out to define the CV risks associated with COXIBs and NSAIDs. All COX inhibitors had shown this CV toxicity. In many clinical studies, rofecoxib use was associated with significantly more elevated CV risk when compared with celecoxib and non selective NSAIDs. The COX inhibitors associated CV toxicity has multiple manifestations, which include the induction of myocardial infarction (MI), edema, thrombosis, blood pressure destabilization and death. Patients at risk of CV disease or with a history of CV disease were the most significant determinants of CV events after receiving COX inhibitors. This CV toxicity not only led to the marketing withdrawal of rofecoxib and valdecoxib but also resulted in more restricted, but essentially identical, product labels in the United States for celecoxib and traditional NSAIDS. This CV toxicity is dose and treatment duration dependent and appears to be compound specific rather than COX specific. Additional comprehensive, long-term, prospective investigations comparing the CV and GI safety profile of marketed NSAIDs against each other and against selective inhibitors are needed to address the controversy of COX inhibitors.

2

Roles of cellular polyamines in mucosal healing in the gastrointestinal tract

84%

Gao J.-H., Guo L.-J., Huang Z.-Y., Rao J. N., Tang C.-W.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 6

3

Oral inoculation of live or dead third-stage larvae of Anisakis simplex in rats suggests that only live larvae induce production of antibody specific to A. simplex

84%

Abe N., Teramoto I.

Acta Parasitologica

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2014

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tom 59

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nr 1

Live Anisakis simplex third-stage larvae (L3) penetrate gastrointestinal mucosa after they are ingested in raw or undercooked seafood, thereafter causing gastrointestinal manifestations and allergic manifestations such as urticaria and anaphylaxis. These allergic reactions are mediated by specific IgE to L3 allergens, especially excretory-secretory (ES) allergens. Recent evidences suggest that only live larvae can cause allergic reactions, although cases attributable to ingestion of cooked, frozen seafood have been reported. Therefore the risk of Anisakis-associated hypersensitivity by ingestion of properly cooked and frozen fish remains controversial. No prior report describes the kinetics of antibody production in experimental animals after oral inoculation with dead L3. This study used ELISA to assess antibody production in rats inoculated orally with dead L3. Positive absorbance value in IgG, IgM, and IgE specific to ES antigen from L3 were found in rats inoculated with live L3 but not with dead L3 (frozen, heated, cut, or homogenized). At one week post re-inoculation with live or frozen L3 to the initially sensitized rats, the absorbance value of the specific IgM and IgE to ES antigen elevated quickly and highly in rats that had been re-inoculated with live L3, but they decreased slightly or did not change in rats inoculated with frozen L3. These results suggest that only ingestion of live L3 can produce the specific antibody and induce initial and secondary sensitizations to L3.

4

Influence of Viburnum opulus proanthocyanidins on stress-induced gastrointestinal mucosal damage

84%

Zayachkivska O. S., Gzhegotsky M. R., Terletska O. I., Lutsyk D. A., Yaschenko A. M., Dzhura O. R.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 5

155-167

Recent studies demonstrated that the proanthocyanidins (PA), the polymers of flavan-3-ols, naturally occurring plant metabolites widely available in fruits, vegetables, nuts, seeds, flowers and bark, have anti-inflammatory, anticarcinogenic, anti-allergic, antioxidant and vasodilatory actions. We hypothesized that Viburnum opulus PA (VOPA, Caprifoliaceae), due to activation of multifactorial gastrointestinal mucosal defense mechanisms, exert gastroduodenoprotective effects. The aim of the study was: 1) to investigate VOPA effects on gastroduodenal mucosal integrity and pattern of carbohydrate binding proteins and nitric oxide (NO) content in intact mucosa and that exposed to non-topical ulcerogens (stress) in rats without and with capsaicin (125 mg/kg, sc) denervation; and 2), to assess the role of activity of antioxidizing enzymes superoxide dismutase (SOD), catalase (CAT), gluthatione peroxidase (GPx) in VOPA-iduced gastroduodenoprotection against water immersion and restraint stress (WRS) in rats. VOPA was administered orally in dose of 25, 50 or 75 mg/kg body weight. Gastroduodenal mucosal damage detected by routine light microscopic investigation and lectin histochemistry set, purified from plant and animal sources of Carpatian region. NO content, pro-and antioxidant system were determinated by routine laboratory methods. Pretreatment with VOPA afforded gastroduodenoprotection and was accompanied by an increase in NO expression, both changes being reversed by sensory denervation, as well as by the rise of SOD, CAT activity and fall in MDA content. Our study shows that VOPA exerts a potent gastroduodenoprotective activity via an increase in endogenous NO generation, suppression of lipid peroxidation and mobilization of antioxidant activity and changes in glycoconjugate content of the gastroduodenal mucosa of rat.

5

Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves

84%

Konturek S. J., Zayachkivska O., Havryluk X. O., Brzozowski T., Sliwowski Z., Pawlik M., Konturek P. C., Czesnikiewicz-Guzik M., Gzhegotsky M. R., Pawlik W. W.

Journal of Physiology and Pharmacology

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2007

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tom 58

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nr 2

Melatonin (MT) is known to protect gastrointestinal mucosa against various types of injury but its effects on esophageal damage have not been studied. We examined the effects of MT on acute esophageal injury and the mechanism involved in the action of this indole. Acute esophageal lesions were induced by perfusion with acid-pepsin solution using tube inserted through the oral cavity into the mid of esophagus of anaesthetized rats with or without inhibition of prostaglandin (PG) generation by indomethacin (5 mg/kg/day), nitric oxide (NO) formation by NG-nitro-L-arginine (L-NNA, 20 mg/kg/day) or sensory nerves deactivation by capsaicin (125 mg/kg, sc). The esophageal injury was assessed by macroscopic score and histologic activity index. The esophageal mucosal blood flow (EBF) was determinated by H2-gas clearance method. The plasma TNF-alpha and nitrate/nitrite (NOx) levels and mucosal PGE2 contents were assessed by immunoassays. Esophageal acid-pepsin perfusion induced noticeable esophageal mucosal injury as compared to perfusion with vehicle saline. The pretreatment with MT prevented significantly esophageal injury, raised EBF and mucosal content of PGE2, while decreasing the levels of TNF-alpha. Inhibition of COX/PG and NOS/NO systems by indomethacin and L-NNA, respectively, or inactivation of sensory nerves by capsaicin, that manifested in further increase of esophageal injury, reduced the levels of EBF, markedly raised the levels TNF-alpha and reduced mucosal PGE2, but the pretreatment with MT prevented significantly esophageal injury, improved EBF and raised mucosal PGE2 contents. These studies suggest that MT can be considered as a novel esophagoprotector, acting, at least in part, through the COX/PG and NOS/NO systems and activation of sensory nerves.

6

Surveillance of the gastrointestinal mucosa by sensory neurons

84%

Holzer P.

Journal of Physiology and Pharmacology. Supplement

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2001

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tom 52

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nr 2

7

Light and scanning electron microscopy evaluation of the postnatal small intestinal mucosa development in pigs

67%

Skrzypek T., Valverde Piedra J. L., Skrzypek H., Wolinski J., Kazimierczak W., Szymanczyk S., Pawlowska M., Zabielski R.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 3

71-87

Modifications in the structure of gastrointestinal mucosa is often used to evaluate gut function for instance during the development or in response to particular food components. Scanning electron microscopy (SEM) gives a chance to observe the surface of the gut epithelium in three dimensions. However, this technique is seldom used due to technical difficulties. The present study attempted to investigate the intestinal mucosa structure changes in the postnatal pig using light and scanning electron microscopy technique. Experiments were carried out on sow reared piglets from birth until 38 days of age. Piglets were sacrificed at birth and at the 3rd, 7th, 21st and 38th day of life. The entire gastrointestinal tract was immediately harvested and the whole thickness tissue samples were taken from the duodenum, jejunum and ileum for optical and scanning electron microscopy. SEM analyses corroborated with histometry made by optical microscopy. Moreover, a number of shape modifications of the villi and its surface have been observed. The development changes in small intestine mucosa during the first 3 weeks were manifested in shape, size and density of villi. In conclusion, the structure of small intestinal mucosa undergoes profound structural changes. SEM gives a new dimension in the investigation of gut mucosa.

8

Gastric cytoprotection by prostaglandin E2 and prostacyclin: relationship to EP1 and IP receptors

67%

Takeuchi K.

Journal of Physiology and Pharmacology

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2014

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tom 65

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nr 1

9

Effect of sodium butyrate on the small intestine development in neonatal piglets feed by artificial sow

67%

Kotunia A., Wolinski J., Laubitz D., Jurkowska M., Rome V., Guilloteau P., Zabielski R.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

59-68

Feeding of neonates with artificial milk formulas delays the maturation of the gastrointestinal mucosa. Na-butyrate has a complex trophic effect on the gastrointestinal epithelium in adults. The present study aimed to determine the effect of milk formula supplementation with Na-butyrate on the gut mucosa in neonatal piglets. Sixteen 3 day old piglets were randomly divided into two groups: control (C, n = 8), and Na-butyrate (B, n = 8). Animals were feed for 7 days with artificial milk formula alone (C) or supplemented with Na-butyrate (B). At the 10th day of life the piglets were sacrificed and whole thickness samples of the upper gut were taken for analyses. Administration of Na-butyrate led to significant increase in daily body weight gain as compared to control. In the duodenum, the villi length and mucosa thickness were reduced, however, in the distal jejunum and ileum, the crypt depth, villi length and mucosa thickness were increased in Na-butyrate supplemented piglets as compared to control. Supplementation with Na-butyrate did not affect the intestinal brush border enzyme activities but increased plasma pancreatic polypeptide and cholecystokinin concentrations. These results suggest that supplementation with Na-butyrate may enhance the development of jejunal and ileal mucosa in formula-fed piglets.

Ograniczanie wyników

Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man

Roles of cellular polyamines in mucosal healing in the gastrointestinal tract

Oral inoculation of live or dead third-stage larvae of Anisakis simplex in rats suggests that only live larvae induce production of antibody specific to A. simplex

Influence of Viburnum opulus proanthocyanidins on stress-induced gastrointestinal mucosal damage

Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves

Surveillance of the gastrointestinal mucosa by sensory neurons

Light and scanning electron microscopy evaluation of the postnatal small intestinal mucosa development in pigs

Gastric cytoprotection by prostaglandin E2 and prostacyclin: relationship to EP1 and IP receptors

Effect of sodium butyrate on the small intestine development in neonatal piglets feed by artificial sow