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Double-blind crossover study of ranitidine and ebrotidine in gastro-esophageal reflux disease

100%

Sito E., Thor P. J., Maczka M., Lorens K., Konturek S. J., Maj A.

Journal of Physiology and Pharmacology

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1993

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tom 44

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nr 3

2

Does the established cause of chronic cough depend on diagnostic approach?

86%

Grabczak E. M., Dabrowska M., Krenke R., Domeracka-Kolodziej A., Domagala-Kulawik J., Arcimowicz M., Hamera M., Chazan R.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 6

285-296

3

Lansoprazole is an uncompetitive inhibitor of tissue-nonspecific alkaline phosphatase

72%

Delomenede M., Buchet R., Mebarek S.

Acta Biochimica Polonica

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2009

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tom 56

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nr 2

301-305

Lansoprazole, a known H+/K+-ATPase inhibitor, is currently used as a therapeutical option for the initial treatment of gastroesophageal reflux disease. Recently, lansoprazole has been found to be an inhibitor of cytosolic PHOSPHO1 (a phosphatase which hydrolyses phosphocholine and phosphoethanolamine), providing a possible therapeutical target to cure pathological mineralization. Since PHOSPHO1 is present inside matrix vesicles, we tested the effect of lansoprazole on matrix vesicles containing several key enzymes for the mineralization process including tissue-nonspecific alkaline phosphatase. We found that lansoprazole can inhibit in an uncompetitive manner tissue-nonspecific alkaline phosphatase. A Ki value of 1.74 ± 0.12 mM has been determined for the inhibition of tissue-nonspecific alkaline phosphatase by lansoprazole. Lansoprazole, currently used for treating gastroesophageal disease, by inhibiting PHOSPHO1 and tissue-nonspecific alkaline phosphatase could prevent hydroxyapatite-deposition disease and could serve as an adjunct treatment for osteoarthritis.

4

Barrett's esophagus associates with a variant of IL23R gene

72%

Gaj P., Mikula M., Wyrwicz L. S., Regula J., Ostrowski J.

Acta Biochimica Polonica

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2008

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tom 55

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nr 2

365-369

Gastroesophageal reflux disease is regarded as a spectrum of diseases: non-erosive reflux disease (NERD), erosive reflux disease (ERD), and the far end of the spectrum represented by patients with Barrett’s esophagus. Among predisposing factors, both risk and protective polymorphic variants of several genes may influence the clinical outcomes of reflux disease. Consequently, different molecular mechanisms are likely to underlie the development of clinical variants of reflux disease. Ninety six patients with reflux disease were screened for polymorphisms of CARD15, SLC22A4 (OCTN1), SLC22A5 (OCTN2), DLG5, ATG16L1 and IL23R genes which had previously been found to associate with immune-mediated chronic inflammatory disorders. While none of the polymorphisms were associated with NERD or ERD, the 1142G/A variant of the IL23R gene was found to be a risk variant in Barrett’s esophagus patients. The IL23/IL23R pathway may modulate STAT3 transcriptional activity which is an essential regulator not only of immune-mediated inflammation, but also of inflammatory-associated apoptosis resistance. Although the mechanisms of metaplastic transition of inflamed squamous epithelium are undetermined as yet, our findings suggest potential involvement of alternations in the IL23/IL23R pathway as a molecular background of Barrett’s esophagus development.

5

Disturbances of the parasympathetic branch of the autonomic nervous system in patients with gastroesophageal reflux disease [GERD] estimated by short-term heart rate variability recordings

72%

Dobrek L., Nowakowski M., Mazur M., Herman R. M., Thor P. J.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

77-90

Gastro-esophageal reflux disease (GERD) is the result of the acid contents regurgitation back from the stomach into the esophagus. According to the endoscopic findings, GERD can be divided into two main forms: non-erosive (NERD) and erosive reflux esophagitis. The pathogenesis of GERD is associated with the impaired function of the antireflux barrier. Disturbances of the autonomic nervous system (ANS), especially parasympathetic part of the ANS, may be also involved in the pathogenesis of this disease. The aim of our study was to establish the parasympathetic activity in patients with reflux esophagitis and in patients with symptomatic endoscopically negative reflux. Working hypothesis was the question, whether the possible parasympathetic activity disturbances, which are observed in all GERD patients, may be regarded as the primary or secondary to the esophagitis. All the participants (20 pts. with NERD, 20 pts. with reflux esophagitis and 20 healthy controls) underwent esophageal manometry, 24-hour ambulatory pH-monitoring, resting heart rate variability (HRV) recording and the deep breathing (DB) test with the continuous HRV recording. The results of the spectral analysis both of the short-term, resting HRV recordings and DB-evoked revealed the disturbances of the main power spectra components - LF and HF in both groups of patients in comparison with the control group. In our opinion, the observed HRV spectra changes in both groups of patients support the hypothesis that not only is the parasympathetic activity impairment associated with the pathogenesis of GERD but it is also the primary factor contributing to the pathophysiological mechanism of reflux.

6

Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease

72%

Thor P. J., Blaut U.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 3

81-90

Gastroesophageal reflux disease (GERD) refers to the very common and constantly increasing conditions where reflux of gastric contents into the esophagus leads to development of characteristic symptoms. The esophagus, LES and stomach can be envisioned as single functional unit controlled by neuro-hormonal factors. The abnormalities that contribute to GERD can start in any component of this unit, resulting particularly from disturbances in their control system. It is extremely important to identify factors and mechanisms leading to functional failure of this system so that causative therapy can be effectively applied. The key-role has been attributed to parasympathetic dysfunction, which may adversely affect motor activity of this area by increasing transient LES relaxation number and impairing LES pressure, esophageal acid clearance and motility of the proximal stomach. Recently, numerous investigations have been performed to elucidate the role of Helicobacter pylori (Hp) infection in GERD pathogenesis with the most concern given to its potency to increase gastric acid secretion. However, it appeared that this infection leads to much more complex changes in gastric mucosa including modification of afferent neural signals and specific gastric hormones release. Plasma ghrelin level is low in subjects infected and increases significantly after eradication. Since ghrelin, beside potency to increase gastric secretion has strong prokinetic action on LES functional unit, this phenomenon together with impaired vagal control may contribute to the Hp infection or eradication - related GERD development. Thus, ghrelin and vagal activity could be the missing links that partially explains relationship between GERD and Hp infection.

7

Study with two prokinetics in functional dyspepsia and GORD: Domperidone vs. Cisapride

72%

Halter F., Staub P., Hammer B., Guyot J., Miazza B. M.

Journal of Physiology and Pharmacology

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1997

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tom 48

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nr 2

8

Cough reflex sensitivity in children with suspected and confirmed gastroesophageal reflux disease

58%

Varechova S., Mikler J., Murgas D., Dragula M., Banovcin P., Hanacek J.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 5

9

Cyclooxygenase-2 [COX-2] is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects

58%

Majka J., Rembiasz K., Migaczewski M., Budzynski A., Ptak-Belowska A., Pabianczyk R., Urbanczyk K., Zub-Pokrowiecka A., Matlok M., Brzozowski T.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 4

409-418

Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage and inflammation progressing chronic esophagitis and premalignant Barrett's esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects. We evaluated the expression of COX-2 in rat model of BE and examined the usefulness of COX-2 expression in determining the risk of malignant transformation in patients with BE treated with argon plasma coagulation (APC) that allows for effective ablation of metaplastic mucosa (group A) without or with proton pump inhibitors (PPI). In addition, the group B of patients was subjected to laparoscopic Nissen's fundoplication and group K that served as control, received PPI treatment only. Expression of COX-2 was evaluated in fresh-frozen biopsy specimens obtained from the distal esophagus in all 60 patients before and 12 months after treatment. In experimental studies, eighty rats were surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was evaluated by macroscopic and histological index score, the plasma IL-1ß and TNF- levels was determined by ELISA and the mucosal expression of COX-2 mRNA and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic esophagitis was developed in all EGDA animals followed by the rise in the plasma TNF- and IL-1ß levels. Histology revealed extensive esophageal ulcerations with development of columnar epithelium, formation of mucus glands in squamous epithelium, intestinal metaplasia distant to anastomosis consisting of goblet cells, infiltration of inflammatory cells including plasma cells and lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control animals but strongly upregulated in metaplastic Barrett's epithelium. In BE patients, the overexpression of COX-2 was documented in patients with dysplasia. After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2 mRNA was markedly reduced and these effects were positively correlated with histopathological findings. Controls failed to show significant alterations in COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of the chronic esophagitis by the gastrointestinal refluxate resembling many features of those observed in human Barrett's esophagus, as confirmed by severe morphology changes, excessive release of proinflammatory cytokines TNF- and IL-1ß and overexpression of COX-2, and 2) the significant correlation of the degree of COX-2 overexpression with histopathological findings indicates the usefulness of this inducible biomarker as a valuable indicator of the risk of malignant transformation in patients with BE.

10

Nitric oxide (NO)-releasing aspirin exhibits a potent esophagoprotection in experimental model of acute reflux esophagitis. Role of nitric oxide and proinflammatory cytokines

58%

Pawlik M., Pajdo R., Kwiecien S., Ptak-Belowska A., Sliwowski Z., Mazurkiewicz-Janik M., Konturek S. J., Pawlik W. W., Brzozowski T.

Journal of Physiology and Pharmacology

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2011

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tom 62

|

nr 1

The purpose of this study was to develop an acute animal model of reflux esophagitis, which would be suitable to induce the esophageal damage caused by gastric acid reflux, thus mimicking the esophageal injury of human gastroesophageal reflux disease (GERD). Global research indicates that GERD is rapidly increasing among the world's population. NSAIDs are known to induce gastrointestinal damage and low doses of aspirin (ASA) have been shown to increase the incidences of GERD in humans. Gastric acid and pepsin secretion and enhanced COX-2 expression were implicated in the pathogenesis of reflux esophagitis, but the effect of selective COX-2 inhibitors against lesions induced by the reflux of gastric acid content into esophagus has not been thoroughly studied. Here, we compared the effect of aspirin (ASA) and so called "safe" nitric oxide (NO) derivative of ASA with those of non-selective and selective cyclooxygenase (COX)-1 and COX-2 in rat model of reflux esophagitis. Reflux esophagitis was induced in anesthetized rats by ligating the pylorus and limiting ridge transitional region between the forestomach and the corpus of stomach. Subsequently, the total gastric reservoir to store gastric juice was greatly diminished, resulting in the reflux of this juice into the esophagus. Rats with esophagitis received intragastric (i.g.) pretreatment either with: 1) vehicle (saline), 2) ASA or NO-ASA (100 mg/kg); 3) the non-selective COX inhibitor, indomethacin (5 mg/kg); 4) the selective COX-1 inhibitor, SC-560 (10 mg/kg), and 5) the selective COX-2 inhibitor, celecoxib (5 mg/kg). In a separate series of rats with reflux oesophagitis, the efficacy of ASA combined with a donor of NO, glyceryl trinitrate (GTN; 10 mg/kg i.g.) to prevent esophageal mucosal injury was investigated. Four hours after induction of esophagitis the gross mucosal damage was graded with a macroscopic lesion index (LI) from 0-6. The esophageal blood flow (EBF) was determined by H2-gas clearance technique, the oesophageal mucosal and blood samples were collected for histology and analysis of the RT-PCR expression and release of proinflammatory cytokines IL-1ß, TNF- and IL-6 using specific ELISA. The exposure of the esophagus to reflux of gastric acid time-dependently increased the esophageal LI and morphologic damage, and decreased EBF with the most significant changes observed at 4 hrs after the ligation procedure. The pretreatment with native ASA in the dose that suppressed the generation of mucosal PGE2, enhanced gross and histologic esophageal damage and produced a significant fall in EBF. NO-ASA or ASA coupled with GTN counteracted the aggravation of the damage and accompanying fall in EBF when compared with native ASA applied alone to rats with esophagitis. The proinflammatory cytokines IL-1ß and TNF- were overexpressed in rats with esophagitis and those pretreated with ASA but this effect was significantly attenuated by NO-ASA. Plasma IL-1ß, TNF- and IL-6 were negligible in the intact rats but significantly increased in those with esophagitis, with this effect being further enhanced by non-selective (indomethacin) and selective (SC-560, celecoxib) COX-1 and COX-2 inhibitors. We conclude that conventional NSAID such as aspirin augments esophagitis, while NO-ASA exerts the beneficial protective effect against reflux esophagitis via the enhancement of esophageal microcirculation due to NO release and an inhibitory effect on expression and release of pro-inflammatory cytokines.

11

Afferent signalling of gastric acid challenge

58%

Holzer P.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

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nr 4

43-53

Gastric acid is a factor in the pain associated with peptic ulcer and other acid-related disorders including functional dyspepsia, given that antisecretory treatment is a mainstay in the treatment of upper abdominal pain. However, the molecular sensors, afferent pathways and central processing systems of gastric chemonociception are little known. This article reviews emerging evidence that vagal afferent pathways play a pivotal role in gastric chemonociception. Exposure of the rat gastric mucosa to backdiffusing concentrations of luminal acid is signalled to the brainstem, but not spinal cord, as visualized by functional neuroanatomy based on the rapid expression of c-fos. This observation is complemented by the finding that the visceromotor response to gastric acid challenge is suppressed by vagotomy, but not splanchnectomy. The gastric acid-induced expression of c-fos in the brainstem is reduced by inhibition of gastric acid secretion and enhanced by pentagastrin-evoked stimulation of gastric acid secretion. These data indicate that endogenous acid modulates the sensory gain of acid-sensitive vagal afferents. Further consistent with a role of these neurons in gastric nociception is the finding that exposure to proinflammatory cytokines and the induction of experimental gastritis or gastric ulceration sensitizes vagal afferent pathways to gastric acid. Taken together, these observations are of relevance to the understanding and treatment of gastric hyperalgesia and dyspeptic pain.

12

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence of the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines

58%

Pawlik M. W., Kwiecien S., Pajdo R., Ptak-Belowska A., Brzozowski B., Krzysiek-Maczka G., Strzalka M., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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2014

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tom 65

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nr 6

13

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options

51%

Konturek P. C., Brzozowski T., Konturek S. J.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 6

Ograniczanie wyników

Double-blind crossover study of ranitidine and ebrotidine in gastro-esophageal reflux disease

Does the established cause of chronic cough depend on diagnostic approach?

Lansoprazole is an uncompetitive inhibitor of tissue-nonspecific alkaline phosphatase

Barrett's esophagus associates with a variant of IL23R gene

Disturbances of the parasympathetic branch of the autonomic nervous system in patients with gastroesophageal reflux disease [GERD] estimated by short-term heart rate variability recordings

Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease

Study with two prokinetics in functional dyspepsia and GORD: Domperidone vs. Cisapride

Cough reflex sensitivity in children with suspected and confirmed gastroesophageal reflux disease

Cyclooxygenase-2 [COX-2] is the key event in pathophysiology of Barrett's esophagus. Lesson from experimental animal model and human subjects

Nitric oxide (NO)-releasing aspirin exhibits a potent esophagoprotection in experimental model of acute reflux esophagitis. Role of nitric oxide and proinflammatory cytokines

Afferent signalling of gastric acid challenge

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence of the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options