Biomedical subjects

J Piotrowski

Publications and source records attributed to J Piotrowski.

At least 55 records · Page 3Linked to original sources

PubMed1998

Effect of chronic alcohol ingestion on buccal mucosal expression of bFGF and Cdk2 during ulcer healing.

In this study, we investigated the effect of chronic alcohol ingestion on the interplay between the receptor-bound basic fibroblast growth factor (bFGF-R) and the expression of cyclin-dependent kinase (Cdk2) in buccal mucosa during ulcer healing. Chronic ulceration was induced by a topical application of acetic acid to the buccal mucosa of rats maintained for 5 weeks on alcohol-containing or control liquid diet. In both groups, the ulcer healing was accompanied by an increase in buccal mucosal expression of bFGF and Cdk2. In the control group, the ulcer healed within 10 days and maximum induction in bFGF (2.6-fold) and Cdk2 (2.4-fold) occurred by the 2nd day of healing. In contrast, the alcohol diet group showed a marked delay in ulcer healing (14 days), associated with the shift in maximum of bFGF and Cdk2 expression to the 4-6th day, and the values were reduced by 35 to 38%. The findings show that chronic alcohol ingestion exerts detrimental effect on the signaling events initiated by bFGF-receptor activation and propagated by Cdk2 that propels the cell cycle progression essential for rapid mucosal repair.

Acetic Acid↗

PubMed1998

Induction of caspase-3 and nitric oxide synthase-2 during gastric mucosal inflammatory reaction to Helicobacter pylori lipopolysaccharide.

Helicobacter pylori lipopolysaccharide is recognized as a primary virulence factor evoking acute mucosal inflammatory reaction associated with H. pylori infection. We investigated the activity of a key apoptotic protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS-2) during H. pylori lipopolysaccharide-induced acute gastritis. The assays conducted 4 days following intragastric dose of the lipopolysaccharide revealed a pattern of acute mucosal responses characterized by an 11.2-fold increase in epithelial cells apoptosis, inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by a 5.4-fold increase in caspase-3 activity, while the mucosal expression of NOS-2 showed a 6.5-fold induction. The results implicate H. pylori lipopolysaccharide in the induction of NOS-2 expression, and point to its effect on activation of the signaling cascade involving caspase-3 in the process gastric epithelial cells apoptosis.

Acute Disease↗

PubMed1998

Role of basic fibroblast growth factor in the suppression of apoptotic caspase-3 during chronic gastric ulcer healing.

BACKGROUND: In the course of ulcer healing an array of factors compel mucosal cells to proliferate, differentiate, and migrate to the site of injury. The recognition of triggering cues requires close interaction between the regulatory proteins integrating the growth factor and cytokine- mediated signals that propel cells through the cycle events, or to signal apoptosis. In this study, we analyzed the interplay between mucosal expression of the receptor-bound basic fibroblast growth factor (bFGF-R) and cyclin-dependent kinase (Cdk2), and the activity of apoptotic protease, caspase-3, and constitutive nitric oxide synthase (cNOS) during chronic gastric ulcer healing. METHODS: The experiments were conducted with gastric mucosa of rats at different stages of acetic acid-induced chronic gastric ulcer healing. RESULTS: The ulcer onset (2 days following injury) was characterized by a massive epithelial apoptosis associated with a 33-fold increase in caspase-3 activity and a 7.6-fold drop in cNOS, while the mucosal expression of Cdk2 fell by an 18% and that of bFGF-R by 12%. The ulcer healing was accompanied by a rapid elevation in bFGF-R and Cdk2, and a slow recovery in cNOS activity, while the caspase-3 activity and epithelial apoptosis showed a marked decline. The bFGF-R and Cdk2 reached their maximums of 2.2-2.3-fold at 4-6 day of healing, while the caspase-3 activity and the apoptotic DNA fragmentation showed a 3-fold decline by the 7th day of healing. However, the activity of cNOS remained about 50% lower than that of the controls. CONCLUSIONS: Taken together, these results provide strong indications that the initial phase of ulcer healing involves the inhibition of apoptotic caspase activities by a signaling events initiated by bFGF-receptor activation and propagated by the regulatory kinases that propel the cell cycle progression. Our findings also point towards participation of cNOS in the suppression of proapoptotic activities in gastric mucosa.

Animals↗

PubMed1998

Lipopolysaccharide a virulence factor of Helicobacter pylori: effect of antiulcer agents.

Helicobacter pylori plays a major role in the pathogenesis of gastric disease. The gastric epithelial integrity is compromised by the H. pylori cell wall lipopolysaccharide untoward effect on the gastric epithelial cell receptors interaction with proteins of extracellular matrix, glycoproteins of mucus coat, and bioactive peptides. These interactions cause the weakening of the mucus coat rendering the underying epithelium vulnerable to noxious luminal contents and disrupting the regulatory feedback of somatostatin and gastrin. Moreover, H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and these changes are reflected in the increased epithelial cell apoptosis. These findings thus identify cell wall lipopolysaccharide as a virulent factor responsible for the H. pylori effect on gastric epithelium. The effect of antiulcer agents on the interference of lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding. In the case of somatostatin-receptor binding, sulglycotide followed by sucralfate and ebrotidine showed the most potency in of reversing the effect of H. pylori lipopolysaccharide. Thus these antiulcer agents have a great promise in the treatment gastric diseases associated with H. pylori infection.

Anti-Ulcer Agents↗

PubMed1997

Inhibition of the 26 S proteasome by polyubiquitin chains synthesized to have defined lengths.

Ubiquitin is a covalent signal that targets cellular proteins to the 26 S proteasome. Multiple ubiquitins can be ligated together through the formation of isopeptide bonds between Lys48 and Gly76 of successive ubiquitins. Such a polyubiquitin chain constitutes a highly effective proteolytic targeting signal, but its mode of interaction with the proteasome is not well understood. Experiments to address this issue have been limited by difficulties in preparing useful quantities of polyubiquitin chains of uniform length. We report a simple method for large scale synthesis of Lys48-linked polyubiquitin chains of defined length. In the first round of synthesis, two ubiquitin derivatives (K48C-ubiquitin and Asp77-ubiquitin) were used as substrates for the well characterized ubiquitin-conjugating enzyme E2-25K. Diubiquitin blocked at the nascent proximal and distal chain termini was obtained in quantitative yield. Appropriately deblocked chains were then combined to synthesize higher order chains (tetramer and octamer in the present study). Deblocking was achieved either enzymatically (proximal terminus) or by chemical alkylation (distal terminus). Chains synthesized by this method were used to obtain the first quantitative information concerning the influence of polyubiquitin chain length on binding to the 26 S proteasome; this was done through comparison of different length (unanchored) polyubiquitin chains as inhibitors of ubiquitin-conjugate degradation. K0.5 was found to decrease approximately 90-fold, from 430 to 4.8 microM, as the chain was lengthened from two to eight ubiquitins. The implications of these results for the molecular basis of chain recognition are discussed.

Alkylation↗

PubMed1997

Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori lipopolysaccharide with ebrotidine and sulglycotide.

1. Among the consequences of H. pylori infection is an increase in gastric acid secretion due to the impairement in feedback inhibition by somatostatin. Here, we show that lipopolysaccharide from H. pylori inhibits the binding of somatostatin to gastric mucosal receptor, and that antiulcer agents, ebrotidine and sulglycotide, are capable of countering this effect. 2. The somatostatin receptor was prepared from the solubilized gastric mucosal epithelial cell membranes by affinity chromatography on Affi-Gel-bound [D-Tryp8] SRIF-14 and used in the binding assays for 125I-labeled somatostatin in the presence of H. pylori lipopolysaccharide and antiulcer agents. 3. The assays revealed a dose-dependent inhibition in the receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. The effect of H. pylori lipopolysaccharide was countered by ebrotidine and sulglycotide, which at their optimal doses produced 94.9% and 84% restoration in somatostatin-receptor binding, respectively. 4. The results demonstrate that the antiulcer agents, ebrotidine and sulglycotide, possess the ability to counteract the H. pylori interference with somatostatin regulatory effect on gastric acid secretion.

Animals↗

PubMed1997

Cell cycle progression during gastric ulcer healing by ebrotidine and sucralfate.

1. The effect of antiulcer agents, ebrotidine and sucralfate, on the expression of gastric mucosal proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase (p34Cdk2) during chronic ulcer healing was examined. 2. Rats with experimentally induced gastric ulcers were treated twice daily for 14 days with either ebrotidine at 100 mg/kg, sucralfate at 100 mg/kg or vehicle, and at different stages of treatment their stomachs were used for quantitization of gastric mucosal PCNA and Cdk2 expression. 3. The assays revealed that the ulcer healing was accompanied by a marked elevation in mucosal expression of PCNA and Cdk2. The maximum increase in PCNA (4.7-fold) occurred by the second day of healing, and the expression of Cdk2 reached a maximum increase (2.3-fold) by the fourth day. 4. Accelerated ulcer healing with ebrotidine (7 days) and sucralfate (8 days) treatments was reflected in a significant enhancement of PCNA and Cdk2 expression. By the second day of treatment, ebrotidine evoked a 15-fold increase in PCNA expression, and sucralfate produced an 11.8-fold enhancement. The mucosal expression of Cdk2 attained a maximum of 4.3-fold increase over that of the controls by the sixth day of healing with ebrotidine, and a fivefold increase in Cdk2 expression occurred by the fourth day of ulcer treatment with sucralfate. 5. The findings implicate cell cycle regulatory proteins in the processes to leading to mucosal repair and suggest that the two drugs exert a similar effect on the expression of proteins that control cell cycle progression.

Animals↗

PubMed1997

Impact of particulate contamination in crystalloid cardioplegic solutions: studies by scanning and transmission electron microscopy.

The amount of particulate matter present in Bretschneider's cardioplegic solution (HTK) was assessed by laser-mediated particle counting. Permissible levels of contaminant particles with a distribution of diameters between 0.2 and 20 microns were found. A significant further increase in the particle count was observed when the fluid was administered for clinical use, which resulted in the additional release of particles from, for example, the infusion kit, which included an in-line filter with pores of 270 microns. Filtration of the HTK solution by a terminal inline filter (0.2 micron) significantly reduced the number of particles. In order to determine the chemical composition and the potential hazards of the particulate material we used scanning electron microscopy in combination with energy dispersive X-ray analysis and transmission electron microscopy to examine specimens taken from heart tissue obtained from Göttinger minipigs after cardioplegia and from humans undergoing mitral valve replacement after cardioplegia and reperfusion. Particles of various diameters were found either to be plugging coronary capillaries, to be adherent to the endothelial layer, or to be engulfed by polymorphonuclear (PMN) granulocytes, which appeared to be activated. Some of the PMN granulocytes were apparent in the endothelial layer. It is recommended, therefore, that a terminal in-line filter (0.2 micron) should be routinely used.

Animals↗

PubMed1997

Suppression of Helicobacter pylori urease activity by sucralfate and sulglycotide.

The effect of gastroprotective agents, sucralfate and sulglycotide, on the in vitro activity of H. pylori urease was investigated. The bacterium was subjected to sonication, centrifuged, and the supernatant used as an enzyme source. The assays revealed that the rate of urea degradation was proportional to enzyme protein up to 100 micrograms and remained constant with time for 10 min. Introduction of sucralfate or sulglycotide to the assay system led to the reduction in the rate of ammonia production. With both drugs the optimal inhibition was attained at 10 micrograms/ml, at which dose a 63.1% decrease in urease activity occurred with sucralfate and a 70.2% inhibition was obtained with sulglycotide. The findings demonstrate that the inhibitory action of sucralfate and sulglycotide on H. pylori urease activity may be of value in the treatment of gastric disease associated with H. pylori infection.

Ammonia↗

PubMed1997

Gastric mucosal apoptosis induced by ethanol: effect of antiulcer agents.

In this study, we investigated gastric epithelial cells' apoptosis and tumor necrosis factor-alpha (TNF-alpha) expression with ethanol-induced mucosal injury, and the effect of antiulcer agents on this process. Rats received intragastric pretreatment with the agent or vehicle followed 1h later by ethanol, and after 30 min the gastric mucosa was assessed for TNF-alpha and apoptosis. In the absence of antiulcer agents, ethanol caused extensive mucosal lesions accompanied by a 9.5-fold enhancement in apoptosis and a 2.5-fold increase in TNF-alpha. Pretreatment with omeprazole evoked a 54% reduction in TNF-alpha, but had no effect on ethanol-induced mucosal damage or apoptosis, the sucralfate reduced the extent of mucosal damage by 95%, apoptosis by 39% and TNF-alpha by 52%, while ebrotidine not only prevented mucosal injury and rise in TNF-alpha, but also caused a 70% reduction in epithelial cells' apoptosis. The results demonstrate that ethanol-induced gastric epithelial cells apoptosis triggered by the enhancement in mucosal TNF-alpha is efficiently counteracted by ebrotidine.

Animals↗

PubMed1997

Helicobacter pylori lipopolysaccharide inhibition of gastric somatostatin receptor: effect of sucralfate.

In this study, we investigated the inhibitory effect of Helicobacter pylori lipopolysaccharide on the binding of somatostatin to gastric epithelial cell membrane receptor, and assessed the effect of antiulcer agent, sucralfate, on this process. The assays conducted with the somatostatin receptor, purified from the solubilized epithelial cell membranes by affinity chromatography on Affi-Gel-[D-Tryp8]SRIF-14, revealed a dose-dependent inhibition in receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. This effect of H. pylori lipopolysaccharide was countered by sucralfate that produced a 92.5% restoration in receptor-somatostatin binding at 70 micrograms/ml of the drug. The findings demonstrate that sucralfate is capable of reversing the interference by H. pylori lipopolysaccharide with somatostatin-receptor binding on gastric mucosal G-cells.

Animals↗

PubMed1997

Effect of ethanol on gastric mucus glycoprotein synthesis, translocation, transport, glycosylation, and secretion.

The effect of ethanol on mucus glycoprotein synthesis, intracellular modification, transport, glycosylation, and secretion was studied in rat gastric mucous cells. Preincubation of the in vitro translation mixture containing gastric mucous cells mRNA for 60 min with 0 to 120 mM ethanol caused a decrease in the synthesis of mucus glycoprotein apopeptide by up to 40%. The reduction in translation was time- and ethanol concentration-dependent. After 60 min, translation in the presence of 30, 60, and 120 mM ethanol decreased to 83.3 +/- 2.3%, 75.5 +/- 0.4%, and 63.6 +/- 2.6%, respectively. The experiments conducted with endoplasmic reticulum microsomes, preincubated with ethanol, and used in the studies of cotranslational translocation of the apomucin showed a 20% decrease in the transfer of mucus glycoprotein apopeptide to the lumen of endoplasmic reticulum microsomes. In the presence of ethanol, processing of mucus glycoprotein apopeptide in Golgi was also inhibited. During the initial 30 min of incubation with 0 to 120 mM ethanol, glycosylation seemed to proceed at the same rate in the samples with and without ethanol. However, during consecutive 30 min of incubation, glycosylation in the presence of 60 mM ethanol decreased by 30 to 35%, and with 120 mM ethanol was completely inhibited. Measurements of the effect of ethanol on the discharge of mucus glycoprotein from the intracellular stores revealed that, on average, the secretory output of the rat gastric mucosa exposed to ethanol liquid diet for 8 weeks decreased by 77% or more, and adherence of the glycoprotein to the gastric epithelium was weakened. Results indicate that ethanol inhibits synthesis, transport, and processing of gastric mucus glycoprotein, and that the processes taking place in different intracellular compartments contribute in the additive fashion and, are reflected in a dramatic decrease in the delivery of mucus glycoprotein to the gastric epithelial surfaces.

Animals↗

PubMed1997

Induction of tumor necrosis factor-alpha and apoptosis in gastric mucosal injury by indomethacin: effect of omeprazole and ebrotidine.

BACKGROUND: The gastric injury associated with nonsteroidal anti-inflammatory drug (NSAID) therapy has been linked to the detrimental effects of the agents on the processes of prostaglandin generation, leukocyte adherence, superoxides production, and mucosal cell proliferation. In the present study we investigated the expression of tumor necrosis factor-alpha (TNF-alpha) and epithelial cell apoptosis during indomethacin-induced gastric mucosal injury and evaluated the effect of two antiulcer agents on this process. METHODS: The experiments were carried out with groups of rats subjected to intragastric pretreatment with 40 mg/kg omeprazole, 100 mg/kg ebrotidine, or vehicle, followed 30 min later by an intragastric dose of indomethacin at 60 mg/kg. After 2 h the animals were killed, and the gastric mucosal tissue used for macroscopic damage assessment, quantitation of TNF-alpha expression, and the assay of epithelial cell apoptosis. RESULTS: In the absence of antiulcer drugs, indomethacin caused extensive multiple hemorrhagic lesions accompanied by a 47% increase in mucosal expression of TNF-alpha and a dramatic (> 300-fold) enhancement in gastric epithelial cell apoptosis. Pretreatment with a proton pump inhibitor, omeprazole, produced only marginal (6-8%) reduction in the extent of mucosal damage caused by indomethacin, whereas the mucosal expression of TNF-alpha decreased by 15% and the apoptotic DNA fragmentation by 10-13%. In contrast, the H2-receptor antagonist ebrotidine, also known for its gastroprotective effects, not only successfully prevented (98.3%) the enhancement in mucosal TNF-alpha expression caused by indomethacin but also caused a 54% reduction in the epithelial cell apoptosis. These effects of ebrotidine were, furthermore, reflected in a 90.2% prevention in the gastric mucosal damage. CONCLUSIONS: Our findings provide new insights into the mechanism of gastric injury caused by NSAIDs and show that ebrotidine protection against indomethacin-induced mucosal damage occurs through the inhibition of epithelial cell apoptosis triggered by the enhancement in the mucosal TNF-alpha expression. Our data also show that omeprazole does not possess antiapoptotic properties.

Animals↗

PubMed1997

Induction of acute gastritis and epithelial apoptosis by Helicobacter pylori lipopolysaccharide.

BACKGROUND: The preservation of gastric mucosal homeostasis is a complex biologic process, controlled by a dynamic equilibrium of cell loss by apoptosis with that of cellular proliferation, and its abrogation is a prominent feature of Helicobacter pylori-associated gastritis. In this report, we show that H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and that these changes are reflected in the increased epithelial cell apoptosis. METHODS: The experiments were conducted with groups of rats subjected to intragastric surface epithelial application of the lipopolysaccharide at 50 and 200 micrograms per animal. The histologic assessment of the mucosal tissue and quantification of apoptotic epithelial cells was performed 2 and 10 days after the lipopolysaccharide treatment. RESULTS: Histologic examination showed that H. pylori lipopolysaccharide at both doses within 2 days induced infiltration of lamina propria with lymphocytes and plasma cells, edema, hyperemia, and hemorrhage extending from the lamina propria to the surface of mucosa, and the effect persisted beyond the 10 days. The in situ DNA fragmentation assay showed that lipopolysaccharide caused a marked increase in epithelial cell apoptosis, with the numerous apoptotic cells present not only in the superficial epithelium but also deeper in the glands. The mean apoptotic index in the mucosa was 59% when assessed 2 days after the administration of the 50-microgram lipopolysaccharide dose and 71.9% after the 200-microgram dose, whereas in the sections assessed 10 days after the lipopolysaccharide treatment the apoptotic index averaged 46% for a 50-microgram dose and 76.8% for a 200-microgram dose. Moreover, the apoptotic index showed positive correlation (r = 0.71) with the grade of the induced inflammatory changes. CONCLUSIONS: Our findings demonstrate that H. pylori lipopolysaccharide can cause gastric mucosal responses typical of acute gastritis and identify the lipopolysaccharide as a virulence factor responsible for the induction of gastric epithelial cell apoptosis by H. pylori.

Animals↗

PubMed1997

Gastric mucosal cell cycle regulation with ulcer healing by sulglycotide.

BACKGROUND: The progression of the events associated with gastric mucosal repair is controlled in an orderly manner by a plethora of the extracellular cues exerting their effect on the cell cycle regulatory proteins, cyclins, and cyclin-dependent kinases, the expression of which varies through the cycle stages. The purpose of this study was to evaluate the expression of cyclin-dependent kinase (Cdk2) and proliferating cell nuclear antigen (PCNA) during chronic ulcer healing with sulglycotide. METHODS: Rats with experimentally induced gastric ulcers were treated twice daily for 14 days either with sulglycotide at 200 mg/kg or vehicle, and at different stages of the treatment their stomachs were used for macroscopic damage assessment and quantitation of gastric mucosal Cdk2 and PCNA expression. RESULTS: The assays showed that the ulcer healing was accompanied by an increase in mucosal expression of Cdk2 and PCNA. The maximum increase in Cdk2 (2.3-fold) occurred by the 4th day of healing. An accelerated ulcer healing (10 days) with sulglycotide treatment was reflected in a marked enhancement in Cdk2 expression attained a maximum 2.1-fold increase by the 6th day of treatment and remained substantially increased for up to 10 days. CONCLUSIONS: The findings show a complex interplay between the extracellular cues and cell cycle regulatory proteins, an orderly progression that drives the mucosal repair process. We also show that the gastroprotective agent sulglycotide is capable of affecting the expression of the cell cycle regulatory proteins that control cell cycle progression through G1 and into S phase.

Animals↗

PubMed1997

Gastroprotective properties of ebrotidine. A review.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a new antiulcer drug which combines the properties of an H2-receptor antagonist with those of a cytoprotective agent. The cytoprotective properties of ebrotidine are not dependent upon endogenous prostaglandin generation, but stem from the ability of the drug to induce mucosal responses manifested in the enhanced physicochemical characteristics of mucus gel. These include the increase in mucus gel dimension, viscosity, hydrophobicity and hydrogen ion retardation capacity. Improvements in mucus gel protective qualities with ebrotidine are directly related to the ability of the drug to enhance the synthesis and secretion of sulfo- and sialomucins and phospholipids of gastric mucus and to promote mucin macromolecular assembly. An equally important property of ebrotidine in promotion of ulcer healing is its capability to enhance the gastric mucosal expression of integrin receptors for the interaction with proteins of the extracellular matrix such as laminin. Furthermore, the accelerated ulcer healing with ebrotidine is reflected in a marked increase in the mucosal expression of EGF and PDGF receptors. The drug has also been shown to modulate the processes associated with cell cycle progression during ulcer healing, and is known to protect the gastric epithelial integrity from calcium imbalance. Thus, ebrotidine, unlike other H2-blockers, has a unique ability to promote the event essential for mucosal repair and the maintenance of mucosal integrity. These features make ebrotidine a drug of great potential in the treatment of ulcer disease.

Animals↗

PubMed1997

Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data.

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.

Animals↗

PubMed1997

Suppression of Helicobacter pylori protease activity towards growth factors by sulglycotide.

Infection with H. pylori is now recognized as a major factor in the pathogenesis of gastric disease. Here, we examined the susceptibility of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF beta) and platelet derived growth factor (PDGF) to degradation by H. pylori protease, and assessed the effect of a cytoprotective agent, sulglycotide, on this process. The 125I-labeled EGF, bFGF, TGF beta and PDGF were incubatet with H. pylori protease, obtained from the filtrates of saline washes of the bacterium culture, in the presence of 0-100 micrograms sulglycotide. The results showed that, under the assay conditions, H. pylori protease caused only 5% degradation of EGF and 7% degradation of bFGF. However, the protease evoked a 61.7% degradation of PDGF and a 62.3% degradation of TGF beta. Introduction of sulglycotide to the reaction assay system caused a dose-dependent inhibition in PDGF and TGF beta proteolysis by the H. pylori enzyme. The maximal inhibitory effect was obtained with sulglycotide at 100 micrograms/ml, at which dose an 84.4% decrease in PDGF and 88.3% decrease in TGF beta degradation was achieved. The results provide a strong evidence for the effectiveness of sulglycotide in the protection of gastric mucosal growth factors against degradation by H. pylori.

Anti-Ulcer Agents↗