transforming-growth-factor-beta and Stomach-Ulcer

Soft corals and their secondary metabolites represent an exceptional source of potential drugs. In this regard, Sarcophyton glaucum-derived secondary metabolites were examined for their preventive activities against indomethacin-induced gastric ulcer. Extraction and chromatographic processing of a specimen of S. glaucum collected from the Red Sea waters of Jeddah city resulted in the isolation of eight metabolites including two furanone-based cembranoids (1 and 2), two known pyran-based cembranoids (3 and 4), a known aromadendrene derivative (5), a δ-lactone fatty acid derivative (6), and two known gorgostane-type sterols (7 and 8). Compounds 1 and 6 are new chemical structures, named Δ

Topics: Animals; Anthozoa; Antioxidants; Diterpenes; Indian Ocean; Indomethacin; Rats; Stomach Ulcer; Transforming Growth Factor beta

Gastric ulcer (GU) is a prevalent chronic digestive disease affecting about 10% of the world's population leading to gastrointestinal perforation and bleeding. Genistein is a legume flavonoid with antioxidants, anti-inflammatory and antibacterial activities. Therefore, we aimed to investigate the ability of genistein to reduce experimentally induced GU in rats by affecting gastric tissue fibrosis Wnt/β-catenin/TGF-β/SMAD4 pathway.. Thirty rats were used. Ten rats served as control, and GU was induced in twenty rats using a single dose of indomethacin (80 mg/kg) orally. Following induction of GU, ten were treated with genistein 25 mg/kg orally. The gastric tissues were isolated to investigate markers of gastric fibrosis, Wnt, β-catenin, transforming growth factor (TGF)-β, SMAD4, and Protein kinase B (PKB). In addition, gastric sections were stained with PAS and anti-TGF-β antibodies.. Investigation GU micro-images revealed degeneration in both surface cells and glandular epithelial cells, which was improved by genistein. In addition, treatment with genistein significantly reduced the expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.. Besides antioxidant activity, genistein improves experimentally induced GU in rats, at least in part, via reduction of gastric tissue fibrosis as indicated by reduction in expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.

Topics: Animals; beta Catenin; Catenins; Fibrosis; Genistein; Rats; Stomach Ulcer; Transforming Growth Factor beta

Aim of the present study was to evaluate in vitro toxicity and in vivo antibacterial, anti-inflammatory, antiulcer, and antioxidant activities of two organoselenium compounds, selenocystine (SeCys) and ebselen (Ebs). The study was conducted in experimentally induced ulcers in rodent model infected with Helicobacter pylori (H. pylori). In vitro toxicological studies on normal splenic lymphocytes revealed that SeCys and Ebs were non-toxic to the cells even at 100 μM concentration. Antibacterial activity was observed at 500 μg/mL concentration of either of the compounds against H. pylori. In vivo studies after treatment with SeCys and Ebs (500 μg/kg/day) resulted in significant reduction in ROS production and inhibition of lipid peroxidation in gastric tissue. The antioxidant and anti-inflammatory activities of both the compounds were also confirmed by their ability to lower GSH reduction, to induce the expression of antioxidant genes such as GPx-4, and MnSOD and to suppress inflammatory genes namely COX-2, TNF-α and TGF-β. In addition, the immunomodulatory activity of both the compounds was evident by enhance of the CD4 levels and maintenance of the IgG, IL-6 and IL-10 levels. Persistent treatment (500 μg/kg, for 28 days) with both the compounds showed considerable (p<0.05) ulcer healing property supporting its role in gastro protection. In conclusion, the results of our study suggest that both SeCys and Ebs possess broad spectrum of activities without any potential toxicity.

Topics: Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Antioxidants; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Helicobacter Infections; Helicobacter pylori; Immunoglobulin G; Interleukin-10; Interleukin-6; Naproxen; Organoselenium Compounds; Oxidative Stress; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Stomach Ulcer; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Zn(II)-curcumin, a mononuclear (1:1) zinc complex of curcumin was synthesized and examined for its antiulcer activities against pylorus-ligature-induced gastric ulcer in rats. The structure of Zn(II)-curcumin was identified by elemental analysis, NMR and TG-DTA analysis. It was found that a zinc atom was coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Zn(II)-curcumin (12, 24 and 48 mg/kg) dose-dependently blocked gastric lesions, significantly reduced gastric volume, free acidity, total acidity and pepsin, compared with control group (P<0.001) and curcumin alone (24 mg/kg, P<0.05). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that Zn(II)-curcumin markedly inhibited the induction of nuclear factor-kappa B (NF-kappaB), transforming growth factor beta(1) (TGF-beta(1)) and interleukin-8 (IL-8), compared with control group (P<0.05). These findings suggested that Zn(II)-curcumin prevented pylorus-ligation-induced lesions in rat by inhibiting NF-kappaB activation and the subsequent production of proinflammatory cytokines, indicating a synergistic effect between curcumin and zinc. An acute toxicity study showed that mice treated with SDs of Zn(II)-curcumin (2 g/kg) manifested no abnormal signs.

Topics: Animals; Anti-Ulcer Agents; Base Sequence; Curcumin; DNA Primers; Dose-Response Relationship, Drug; Interleukin-8; Magnetic Resonance Spectroscopy; Male; Mice; NF-kappa B; Organometallic Compounds; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Stomach Ulcer; Transforming Growth Factor beta

Transforming growth factor-beta (TGF-beta) plays a regulatory role in tissue repair. In a previous study, we found that TGF-beta and its receptors were expressed in gastric mucosa of patients with well-healed gastric ulcers, as demonstrated by immunohistochemistry. To further characterize the role of TGF-beta and its receptors in repairing gastric ulcers, we investigated the expression patterns of TGF-beta and its receptors in gastric mucosa by in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR).. Seventy-four patients with endoscopically proven gastric ulcers were eligible for participation in this study. All patients had routine biopsies on initial endoscopy and were then treated for 12 wk with an H2 blocker. Repeat endoscopy was then performed. There were 8 patients with poorly healed ulcers, and biopsies were taken from the margin of the residual ulcers. These tissue samples, along with biopsy of gastric mucosa near the original ulcers from 8 randomly selected patients with well-healed ulcers were examined for TGF-beta and TGF-beta receptor II mRNA by RT-PCR and in situ hybridization, as well as immunohistochemistry.. TGF-beta and TGF-beta receptor II were strongly expressed in tissues from patients with well-healed ulcers. Four of the 8 patients with poor healing had low or absent expression of TGF-beta or TGF-beta receptor II mRNA. All cases positive by RT-PCR assay were confirmed by in situ hybridization as well as immunohistochemistry.. It is suggested that TGF-beta and its receptors are important for gastric ulcer healing. These results may have implications for further investigation of the healing process and in predicting response to therapy.

Topics: Adult; Aged; Female; Follow-Up Studies; Gastric Mucosa; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Receptors, Transforming Growth Factor beta; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Ulcer; Transforming Growth Factor beta

Transforming growth factor beta3 (TGF-beta3) has been shown to accelerate gastric ulcer healing in rats. However, little is known about the mechanism. In this study we investigated the influence of TGF-beta3 on gastric acid secretion, since gastric hyperacidity is a major cause of gastroduodenal ulcer disease.. Male Sprague Dawley rats were equipped with gastric Thomas cannulas and jugular vein catheters. The acute effect of either intravenous TGF-beta3 (400 and 1200 pg/kg/h) or saline (0.15 M) on pentagastrin-stimulated (10 pg/kg/h) gastric acid secretion was evaluated by gastric acid back-titration after 5 days of recovery. Additionally, pentagastrin-stimulated gastric acid secretion was assessed after 48 hours following TGF-beta3 (1200 microg/kg/h) or saline treatment.. Pentagastrin significantly increased gastric acid production. TGF-beta3 significantly reduced pentagastrin-stimulated gastric acid secretion in a dose-dependent manner as early as 15 minutes after application (saline: 124.9+/-14.9 microEq H+/15 min, TGF-beta3: 97.7+/-13.1 9 microEq H+/15 min, p<0.002). Additionally, pretreatment with TGF-beta3 abolished the effect of pentagastrin on gastric acid production. This effect lasted throughout the entire recording period of 48 hours. However, baseline physiological gastric acid production was not altered by TGF-beta3.. TGF-beta3 inhibits gastric acid secretion when given prior to as well as after pentagastrin treatment. This implicates both a preventive and a therapeutic role of TGF-beta3 in gastroduodenal ulcer disease.

Topics: Animals; Dose-Response Relationship, Drug; Gastric Acid; Gastric Fistula; Humans; Injections, Intravenous; Intubation, Gastrointestinal; Male; Pentagastrin; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stomach Ulcer; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta3; Wound Healing

In order to study the roles of vasoactive peptides during tissue repair of gastric ulcers, we compared concentrations in tissue surrounding gastric ulcers of endothelin-1(ET-1), adrenomedullin (AM), and transforming growth factor-beta (TGF-beta) among different stages of ulcer development. A total of 82 cases were studied. Ulcers were located in the gastric angulus in 51 cases. All cases were positive for Helicobacter pylori (Hp). Ten cases were in the active stage (GA), 18 were in the healing stage (GH), and 28 were in the scarring stage (GS). As control, 17 cases of Hp-positive gastritis (gast+) and 14 of Hp-negative gastritis (gast-) were studied. The concentrations of endothelin (ET) and TGF-beta were in the order of GH> GA> GS, and those of AM were in the order of GS > GH > GA. On immunostaining, ET stained positively in endothelial cells and vascular smooth muscle cells (VSMCs) during the GH and GS stages, and AM stained positively in histiocytes during GA, GH and GS, and also stained positively in glandular epithelia and smooth muscle fibers during GH and GS. When our results were reviewed with respect to the regulation of vascular tonus and the proliferation of VSMCs, ET and AM were considered to have roles in the regulation of proliferation.

Topics: Adrenomedullin; Endothelin-1; Gastric Mucosa; Humans; Immunoenzyme Techniques; Peptides; Stomach Ulcer; Transforming Growth Factor beta; Wound Healing

Transforming growth factor (TGF)-beta regulates cell growth and differentiation, and is known to play regulatory roles in the process of tissue repair and remodeling. However, the functional role of TGF-beta in gastric ulcer healing has not been addressed. In this study, we assayed the expression of TGF-beta and its receptors in the gastric mucosa of patients with healed or refractory gastric ulcers. Antibodies against TGF-beta and its receptors (both type I and type II) were employed to examine expression levels. Sixteen gastric ulcer patients, including four with completely healed ulcers and 12 with ulcers refractory to treatment were included in this study. All four patients with healed ulcers showed remarkable expression levels of both TGF-beta and its receptors. On the other hand, two of the 12 patients with refractory ulcers had weak or deficient TGF-beta expression in the gastric mucosa, and seven lacked expression of at least one of the TGF-beta receptors. The remaining three patients had normal (moderate to weak) expression levels of TGF-beta and its two receptors. These results suggest that both TGF-beta and its receptors are essential for gastric ulcer healing.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastric Mucosa; Humans; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Receptors, Transforming Growth Factor beta; Stomach Ulcer; Transforming Growth Factor beta; Treatment Failure

Fibroblasts modulate epithelial biological activities and play a key role in the ulcer healing process. There is no information regarding the biological response of human gastric fibroblasts to regulatory compounds. The aim of this study was to assess the effects of growth factors and prostaglandins on an in vitro model of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were used to study proliferative responses, determined by [3H]thymidine incorporation into DNA. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of putative growth factors secreted by fibroblasts was studied in conditioned medium by heparin-affinity chromatography and immunodetection with specific antibodies. Serum and platelet-derived growth factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast proliferation and closure of wounded cell monolayers, whereas these activities were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin E1. Basal activities in unstimulated gastric fibroblasts were lower than those obtained in skin fibroblasts. Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was inhibited by the addition of suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is a major, autocrine promotor of human gastric fibroblast-dependent wound repair activities, which are inhibited by prostaglandins and TGF-beta. These findings might be important for future therapeutic ulcer healing approaches.

Topics: Adult; Alprostadil; Cells, Cultured; Culture Media, Conditioned; Epithelium; Fibroblasts; Humans; Immunohistochemistry; Platelet-Derived Growth Factor; Stomach; Stomach Ulcer; Transforming Growth Factor beta; Wound Healing

This study investigated the mRNA expression of transforming growth factor-beta1 (TGF-beta1) and monocyte chemoattractant protein-1 (MCP-1) in rat gastric tissues in which ulcers had relapsed due to interleukin-1beta (IL-1beta) administration. Rats with healed ulcers were administered IL-1beta (1 microg/kg) and killed after 0, 12, 24, or 48 hr. Both TGF-beta1 and MCP-1 mRNA levels were increased in the scarred gastric tissues at 24 hr (fourfold), when ulcers had not relapsed. Furthermore, the expression of these genes also increased in the ulcerated gastric tissues at 48 hr (fivefold), when 90% of healed ulcers had relapsed. On the other hand, the number of macrophages that had infiltrated the scarred gastric tissues at 24 hr was two times higher than that at 0 hr. At 48 hr, the number of macrophages that had infiltrated gastric tissues in which ulcers had relapsed was similar to that at 24 hr. Thus, TGF-beta1 and MCP-1 may be implicated in the macrophage infiltration, thereby leading to ulcer relapse due to IL-1beta.

Topics: Animals; Blotting, Northern; Chemokine CCL2; Disease Models, Animal; Gastric Mucosa; Gene Expression Regulation; Interleukin-1; Macrophages; Male; Monocytes; Rats; Rats, Wistar; Recurrence; RNA, Messenger; Stomach Ulcer; Time Factors; Transforming Growth Factor beta

It has been reported that cyclooxygenase-2 (COX-2) may play a crucial role in gastric ulcer healing. We examined the localization of COX-2 and the regulation of COX-2 mRNA expression in acetic acid ulcers in rats. PGE2 production was elevated in ulcerated tissue but not in intact tissue. COX-2 mRNA expression was induced in only the ulcerated tissue, and COX-2 protein was found in fibroblasts, monocytes/macrophages, and granulocytes. A selective COX-2 inhibitor inhibited increased PGE2 production by the ulcerated tissue. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) mRNAs were also expressed only in the ulcerated tissue. In a culture of isolated ulcer base, blockade of IL-1beta and TNF-alpha reduced COX-2 mRNA expression and PGE2 production. In contrast, COX-2 mRNA expression and PGE2 production were promoted by prevention of TGF-beta1 action. These results indicate that COX-2 protein is highly localized in the base of gastric ulcers in rats and that COX-2 mRNA expression might be regulated positively by IL-1beta and TNF-alpha and negatively by TGF-beta1.

Topics: Acetic Acid; Animals; Antibodies; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Gastric Mucosa; Gene Expression Regulation, Enzymologic; Interleukin-1; Isoenzymes; Male; Prostaglandin-Endoperoxide Synthases; Rats; Reference Values; RNA, Messenger; Stomach Ulcer; Time Factors; Transcription, Genetic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Wound Healing

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow; Bone Marrow Cells; Cell Adhesion; Cytotoxicity, Immunologic; Humans; Indomethacin; K562 Cells; Killer Cells, Natural; Neoplasm Staging; Stomach Neoplasms; Stomach Ulcer; T-Lymphocytes, Regulatory; Transforming Growth Factor beta

To assess the mechanism of the effect of cigarette smoke on ulcer disease we employed a rat model in which cigarette smoke increases the size of acetic acid-induced gastric ulcer and decreases the hyperemia at the ulcer margin. We postulate that cigarette smoke increases angiotensin II (a vasoconstrictor) in ulcer tissue. Since direct measurement of angiotensin II in small tissue samples is problematic, we compared the messenger ribonucleic acid (mRNA) for its precursors (angiotensinogen and renin) in ulcer and normal gastric tissue. We also evaluated the effect of enalapril, which blocks the conversion of angiotensin I to angiotensin II on ulcer size. In the ulcer tissue, cigarette smoke produced a significant increase in mRNA for angiotensinogen but not for renin. Enalapril decreased the size of the gastric ulcer in rats exposed to cigarette smoke. The data support the possibility that in ulcer tissue cigarette smoke stimulates an angiotensin II-mediated mechanism, which may in part be responsible for the impairment of ulcer margin hyperemia and aggravation of ulcer size.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Immunoblotting; Male; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger; Smoking; Somatomedins; Stomach Ulcer; Transforming Growth Factor beta

This study was done to investigate the expression and localization of transforming growth factor-beta1 (TGF-beta1) in the gastric ulcerated tissues produced by acetic-acid during the healing process, by northern blot analysis and immunohistochemical technique. Ulcerated TGF-beta1 mRNA levels were significantly increased from days 3 to 18, in a similar manner to extracellular matrix proteins, and returned to control levels at the scarred phase. Immunoreactive TGF-beta1 was localized in epithelial cells beneath proliferative zone in intact tissues. In ulcerated tissues, TGF-beta1 was localized in macrophages in the ulcer bed and in fibroblasts or myofibroblasts in the granulation tissues. Treatment with prostaglandin E1 (PGE1) further stimulated ulcerated TGF-beta1 expression, being associated with the acceleration of gastric ulcer healing, while treatment with indomethacin reduced TGF-beta1 expression, being accompanied by the delayed ulcer healing. The combination of PGE1 and indomethacin reversed the indomethacin-induced decrease in ulcerated TGF-beta1. Thus, TGF-beta1 may be implicated in the acceleration of gastric ulcer healing.

Topics: Acetic Acid; Alprostadil; Animals; Blotting, Northern; Extracellular Matrix Proteins; Gastric Mucosa; Gene Expression Regulation; Immunohistochemistry; Indomethacin; Male; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Stomach; Stomach Ulcer; Time Factors; Transforming Growth Factor beta; Wound Healing

Barrier-raised transforming growth factor beta 1 (TGF beta 1)-deficient mice consistently die before 35 days of age of a severe multiorgan inflammatory disease that can affect the skeletal muscle, heart, liver, pancreas, salivary gland, lung, oesophagus and stomach. The underlying cause of this disease is not known. To determine whether abnormal responsiveness of the immune system to the presence of enteric flora plays a causative role, a colony of TGF beta 1-deficient and wild-type mice were raised in a sterile environment. Seven germ-free TGF beta 1-deficient and 5 germ-free TGF beta 1 wild-type mice were examined. Lesion development was analysed and compared with historical data on 50 barrier-raised TGF beta 1 mutant mice and 32 barrier-raised wild-type mice. All germ-free TGF beta 1-deficient mice died shortly after weaning, as do their barrier-raised counterparts. There was a significant delay in death in germ-free TGF beta 1-deficient mice compared with barrier-raised mutant mice. However, there was no difference in the type, severity or incidence of lesions between TGF beta 1 mutant mice raised under germ-free or barrier conditions. Germ-free wild-type mice had no lesions. It is concluded that microorganisms play a minimal role in disease induction in TGF beta 1-deficient mice.

Topics: Animals; Germ-Free Life; Hyperplasia; Inflammation; Longevity; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Stomach; Stomach Ulcer; Transforming Growth Factor beta; Ulcer

Gastric ulcer healing is mediated by various endogenous growth factors. In this experimental study effect of locally and systemically applied recombinant human transforming growth factor beta 3 (rhTGF-beta 3) on gastric ulcer healing was investigated in the rat.. Gastric ulcers were induced with a cryoprobe, and ulcer healing was evaluated 7 days after local infiltration (0.5 micrograms, 1.0 microgram, 2.5 micrograms, and 50 micrograms) or systemic (intravenous) application of TGF-beta 3 (500 micrograms/kg body weight). Compared with controls, a dose-dependent stimulation of ulcer healing (as evidenced by a reduction in ulcer size) was observed 7 days after local infiltration of TGF-beta 3 (1.0 microgram, 2.5 micrograms, and 50 micrograms). Corresponding increases in the levels of proliferating cell nuclear antigen (PCNA) and intracellular TGF-beta 3 expression and a downregulation of the TGF-beta type-II receptor expression were also observed in the granulation tissue of the ulcer margins. Systemic application of TGF-beta 3 produced effects similar to those observed after local treatment with 50 micrograms of the compound.. Local and systemic TGF-beta 3 treatment accelerates gastric ulcer healing in rats.

Topics: Animals; Dose-Response Relationship, Drug; Female; Humans; Rats; Rats, Wistar; Recombinant Proteins; Stimulation, Chemical; Stomach Ulcer; Time Factors; Transforming Growth Factor beta; Wound Healing

Transforming growth factor beta 1 (TGF-beta 1) has been shown to play a central role in wound healing. This peptide has been detected in the stomach, but no information is available at present whether TGF-beta 1 influences the healing of gastric ulcers and whether the mucosal expression of TGF-beta 1 changes in the course of this healing. In this study, gastric ulcers were induced by serosal application of acetic acid and TGF-beta 1 or vehicle saline was injected twice into the subserosa around the ulcer area, once immediately after ulcer induction and two days later. Local application of TGF-beta 1 led to significant acceleration of gastric ulcer healing. Gastric blood flow at the ulcer margin was significantly higher than that in the ulcer crater but no significant difference was found in this flow between studied groups. Immunohistochemistry showed that the expression of TGF-beta 1 reached the peak at day 2 and then declined in the course of healing. We conclude that TGF-beta 1 accelerates ulcer healing possibly by increasing the formation of granulation tissue and cell migration probably mediated by locally expressed TGF-beta 1 but the healing effects of TGF-beta 1 do not depend on the vascular factor.

Topics: Animals; Gastric Mucosa; Immunohistochemistry; Male; Neovascularization, Physiologic; Rats; Rats, Wistar; Regional Blood Flow; Stomach Ulcer; Transforming Growth Factor beta; Wound Healing

Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1.. Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed.. The application of NAs to TGF beta 1 led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in the TGF beta 1 treated group.. Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing.

Topics: Animals; Antibodies; Chronic Disease; Male; Rats; Rats, Wistar; Stomach Ulcer; Transforming Growth Factor beta; Wound Healing

Omental implantation, a surgical procedure in which a perforated gastric or duodenal ulcer is repaired by drawing and implanting a portion of the omentum into the digestive tract, accelerates ulcer healing and inhibits ulcer recurrence. However, the mechanisms underlying these beneficial effects are largely unknown. To clarify these mechanisms, we investigated ulcer healing in two groups of rats in which acetic acid-induced gastric ulcers were perforated. Omental implantation was used for repair in one group and simple suturing was employed in the other group. Greater anti-inflammatory and angiogenic activity and accelerated collagen synthesis were seen in the omental implantation group. Basic fibroblast growth factor (bFGF)-mediated angiogenesis was noted in this group, as well as transforming growth factor-beta 1 (TGF-beta 1) activity within and around the omentum, resulting in abundant collagen production. It was confirmed that omental implantation accelerated ulcer healing and inhibited ulcer recurrence, and the presence of bFGF and TGF-beta 1 played a significant role in both these phenomena.

Topics: Animals; Blood Flow Velocity; Cell Count; Disease Models, Animal; Endothelium, Vascular; Fibroblast Growth Factor 2; Fibroblasts; Gastric Mucosa; Immunohistochemistry; Macrophages; Male; Omentum; Peptic Ulcer Perforation; Postoperative Complications; Rats; Rats, Wistar; Recurrence; Stomach Ulcer; Transforming Growth Factor beta