Effect of sucralfate on gastric mucosal blood flow in rats

Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol.published_or_final_versio

Effect of sucralfate on gastric mucosal blood flow in rats

Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol.published_or_final_versio

Epidermal growth factor and its receptor in chronic active gastritis and gastroduodenal ulcer before and after Helicobacter pylori eradication

Background: Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication. Methods: The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression. Results: Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication. Conclusions: Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.link_to_subscribed_fulltex

Improving reproducibility and sensitivity in identifying human proteins by shotgun proteomics

Identifying proteins in cell extracts by shotgun proteomics involves digesting the proteins, sequencing the resulting peptides by data-dependent mass spectrometry (MS/MS), and searching protein databases to identify the proteins from which the peptides are derived. Manual analysis and direct spectral comparison reveal that scores from two commonly used search programs (Sequest and Mascot) validate less than half of potentially identifiable MS/MS spectra (class positive) from shotgun analyses of the human erythroleukemia K562 cell line. Here we demonstrate increased sensitivity and accuracy using a focused search strategy along with a peptide sequence validation script that does not rely exclusively on XCorr or Mowse scores generated by Sequest or Mascot, but uses consensus between the search programs, along with chemical properties and scores describing the nature of the fragmentation spectrum (ion score and RSP). The approach yielded 4.2% false positive and 8% false negative frequencies in peptide assignments. The protein profile is then assembled from peptide assignments using a novel peptide-centric protein nomenclature that more accurately reports protein variants that contain identical peptide sequences. An Isoform Resolver algorithm ensures that the protein count is not inflated by variants in the protein database, eliminating similar to25% of redundant proteins. Analysis of soluble proteins from a human K562 cells identified 5130 unique proteins, with similar to100 false positive protein assignments

TAZ Expression as a Prognostic Indicator in Colorectal Cancer

Agency of Science, Technology, and Research (A*STAR), SingaporeThe Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic,) and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer