Ulcer Length Research Articles

Rabeprazole is effective for bile reflux oesophagitis after total gastrectomy in a rat model.

To elucidate the effect of a proton pump inhibitor (PPI, rabeparazole) on oesophageal bile reflux in oesophagitis after total gastrectomy. Twenty-one 8-week-old male Wistar rats were studied. They were performed oesophagoduodenostomy of total gastrectomy to induce oesophageal reflux of biliary and pancreatic juice. Five rats were performed the sham operation (Sham). On post-operative day 7, they were treated with saline (Control) (n = 8) or PPI (rabeprazole, 30 mg/kg per day, ip ) (n = 8) for 2 wk. On post-operative 21, all rats were sacrificed and each oesophagus was evaluated histologically. Oesophageal injury was evaluated by macroscopic and microscopic findings as well as the expression of cyclooxygenase-2 (COX2). We measured bile acid in the oesophageal lumen and the common bile duct. At 3 wk after surgery, a histological study analysis revealed an increase in the thickness of the epithelium, elongation of the lamina propria and basal cell hyperplasia in the oesophageal mucosa. The macroscopic ulcer score and microscopic ulcer length of the control group were significantly higher compared to those of the rabeprazole- treated group. The expression of COX2 was significantly increased according to the immunostaining in the control group compared to rabeprazole- treated group. Although there was no difference between the control and PPI groups in the total bile acid in the common bile duct, the bile acid activity in the oesophageal lumen was significantly decreased in the rabeprazole- treated group due to augmentation of the duodenal motor complex. With this model, rabeprazole is good effect for reflux esophagitis after total gastrectomy from bile reflux. Bile acid is an important factor in the mucosal lesion induced by duodenal reflux.

Marine hydroquinone zonarol prevents inflammation and apoptosis in dextran sulfate sodium-induced mice ulcerative colitis.

Background and AimWe previously identified an anti-inflammatory compound, zonarol, a hydroquinone isolated from the brown algae Dictyopteris undulata as a marine natural product. To ascertain the in vivo functions of zonarol, we examined the pharmacological effects of zonarol administration on dextran sulfate sodium (DSS)-induced inflammation in a mouse model of ulcerative colitis (UC). Our goal is to establish a safe and effective cure for inflammatory bowel disease (IBD) using zonarol.Methods and ResultsWe subjected Slc:ICR mice to the administration of 2% DSS in drinking water for 14 days. At the same time, 5-aminosalicylic acid (5-ASA) at a dose of 50 mg/kg (positive control) and zonarol at doses of 10 and 20 mg/kg, were given orally once a day. DSS-treated animals developed symptoms similar to those of human UC, such as severe bloody diarrhea, which were evaluated by the disease activity index (DAI). Treatment with 20 mg/kg of zonarol, as well as 5-ASA, significantly suppressed the DAI score, and also led to a reduced colonic ulcer length and/or mucosal inflammatory infiltration by various immune cells, especially macrophages. Zonarol treatment significantly reduced the expression of pro-inflammatory signaling molecules, and prevented the apoptosis of intestinal epithelial cells. Finally, zonarol protected against in vitro lipopolysaccharide (LPS)-induced activation in the RAW264.7 mouse macrophage cell line.ConclusionsThis is the first report that a marine bioproduct protects against experimental UC via the inhibition of both inflammation and apoptosis, very similar to the standard-of-care sulfasalazine, a well-known prodrug that releases 5-ASA. We believe that the oral administration of zonarol might offer a better treatment for human IBDs than 5-ASA, or may be useful as an alternative/additive therapeutic strategy against UC, without any evidence of side effects.

Dipeptidyl peptidase IV inhibition prevents the formation and promotes the healing of indomethacin-induced intestinal ulcers in rats.

We studied the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) as a possible therapy for non-steroidal anti-inflammatory drug (NSAID)-induced intestinal ulcers. Luminal nutrients release endogenous GLP-2 from enteroendocrine L cells. Since GLP-2 is degraded by dipeptidyl peptidase IV (DPPIV), we hypothesized that DPPIV inhibition combined with luminal administration of nutrients potentiates the effects of endogenous GLP-2 on intestinal injury. Intestinal injury was induced by indomethacin (10mg/kg, sc) in fed rats. The long-acting DPPIV inhibitor K579 was given intragastrically (ig) or intraperitoneally (ip) before or after indomethacin treatment. L-Alanine (L-Ala) and inosine 5'-monophosphate (IMP) were co-administered ig after the treatment. Indomethacin treatment induced intestinal ulcers that gradually healed after treatment. Pretreatment with ig or ip K579 given at 1mg/kg reduced total ulcer length, whereas K579 at 3mg/kg had no effect. Exogenous GLP-2 also reduced intestinal ulcers. The preventive effect of K579 was dose-dependently inhibited by a GLP-2 receptor antagonist. Daily treatment with K579 (1mg/kg), GLP-2, or L-Ala+IMP after indomethacin treatment reduced total ulcer length. Co-administration (ig) of K579 and L-Ala+IMP further accelerated intestinal ulcer healing. DPPIV inhibition and exogenous GLP-2 prevented the formation and promoted the healing of indomethacin-induced intestinal ulcers, although high-dose DPPIV inhibition reversed the preventive effect. Umami receptor agonists also enhanced the healing effects of the DPPIV inhibitor. The combination of DPPIV inhibition and luminal nutrient-induced GLP-2 release may be a useful therapeutic tool for the treatment of NSAIDs-induced intestinal ulcers.

Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification

BackgroundThe present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat.MethodsMSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures.ResultsAn increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds.ConclusionMSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

Cold atmospheric argon plasma treatment may accelerate wound healing in chronic wounds: Results of an open retrospective randomized controlled study in vivo

Abstract Previous studies reported a significant reduction in bacterial load in chronic wounds in patients with cold argon plasma. This open retrospective study evaluated effects on wound healing in vivo using the MicroPlaSter alpha device, with wound healing a secondary endpoint. Chronic wounds of various etiologies in 70 patients (Group A) were treated with plasma for 3–7 min. Wound dimensions before and after treatment were compared for plasma-treated and control wounds. Subgroup analyses were performed for all chronic venous ulcers ( n =27, Group B) and 5 min plasma treatment of chronic venous ulcers ( n =18, Group C). Patient acted as own control. In Group A plasma-treated wounds showed a greater reduction in width and length than control wounds. Reduction rates were non-significant. In Group B a significantly greater reduction in width was measured in plasma-treated ulcers compared to controls, but not in ulcer length. Group C showed again a significant reduction in width with plasma treatment but not in ulcer length. This study suggests that wound healing may be accelerated, particularly for chronic venous ulcers.

Uso da ferramenta Pressure Ulcer Scale for Healing para avaliar a cicatrização de úlcera crônica de perna

INTRODUÇÃO: O objetivo deste estudo é descrever a evolução da cicatrização de úlcera crônica de perna, utilizando o instrumento Pressure Ulcer Scale for Healing (PUSH). MÉTODO: Os dados foram coletados no período de julho de 2010 a maio de 2011. A inclusão dos pacientes no estudo obedeceu à ordem de chegada. A lesão foi avaliada semanalmente, sendo aplicada a escala PUSH. RESULTADOS: Foram incluídos no estudo 15 (30%) pacientes diabéticos com pé ulcerado e 35 (70%) pacientes com úlcera venosa. No início da coleta dos dados, a média do comprimento e da largura foi de 9,26, caracterizando que a lesão mensurava de 12,1 cm² a 24 cm². Com 9 meses de tratamento, a úlcera apresentou média de comprimento e de largura de 2,04, caracterizando que a lesão mensurava de 0,3 cm² a 0,6 cm². Com relação à quantidade do exsudato, no início da coleta de dados a média foi de 1,71, caracterizando que a lesão apresentava quantidade moderada e, 9 meses após o início do tratamento, houve redução do exsudato, com média de 0,14, significando ausência de exsudato. Aos 9 meses de tratamento, 19 (38%) pacientes apresentavam úlcera fechada; 17 (34%), úlceras com tecido de granulação; e 14 (28%), tecido epitelizado. CONCLUSÕES: O instrumento PUSH possibilitou acompanhar o processo de cicatrização da lesão por meio da avaliação de comprimento versus largura, quantidade do exsudato e tipo de tecido existente na ferida, favorecendo, assim, a escolha da cobertura ideal para cada fase da cicatrização.

Gastroprotective effect of mummy on induced gastric ulcer in rats

Mummy was used in traditional medicine as a remedy for inflammation, articular injuries, rheumatism, bone fractures, wounds and back pains. In previous research, the healing effects of mummy on a rabbit’s tibial fracture were studied, and the results supported its efficacy. In consideration of claims and suggestions by traditional medicine about the effectiveness of mummy on wound healing, the present study was aimed at investigating the protective effect of mummy on gastric ulcer induced by ethanol. Young male albino rats (NMRI strain, n = 21, 190–230 g body weight) were randomly divided into three experimental groups: treatment group, positive control group and negative control group, each containing seven rats. All animals had been exposed to starvation for 24 h and then received oral ethanol (1 ml/200 g body weight). The treatment group received 100 mg/kg/day mummy; the positive control group received 200 mg/kg/day cimethidine, and the negative control group received 5 ml/kg/day distilled water for 2 weeks by gavages. One hour after the last treatment, all animals were killed, and their stomachs were dissected. The number and length of ulcers were determined using stereomicroscope; then graticule and the ulcer index and curative ratio were calculated. Data was analysed using one-way ANOVA and Tukey’s post hoc test. The administration of mummy significantly decreased the gastric ulcer score and ulcer index in the treatment group, compared with the positive control and negative control groups. The curative ratio in the treatment group was significantly higher than the negative control and the positive control groups (89.26 versus 87.79 %, respectively). The results showed excellent effects of mummy on wound healing after the ethanol-induced gastric ulcer in rats.

Effect of PPI (Rabeprazole) on Reflux Esophagitis after Total Gastrectomy

Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The aim is to clarify the effect of PPI (rabeparazole) on these factors in esophagitis. Sixteen 8-week old male Wistar rats underwent total gastrectomy and esophagoduodenostomy to induce esophageal reflux of duodenal juice. In 5 rats, the sham operation induced a midline laparotomy alone. One week following surgery, they were treated with control (saline) or PPI (rabeprazole) (30mg/kg) ip. Three weeks after operation, all rats were euthanized and the esophagus was evaluated histologically. Esophageal injury was evaluated by macroscopic and microscopic findings, and expression of COX2 and PGE2. Esophageal washing was aspirated for the evaluation of bile acid activity. At 3 weeks after surgery, duodenal reflux induced esophageal erosions and ulcer formation as well as marked thickening of esophageal wall. The macroscopic ulcer score and histological ulcer length were significantly reduced by treatment with rabeprazole. The enhanced expression of COX2 and PGE2 in the control group was also markedly inhibited in the rabeprazole treated group. The bile acid activity in the esophageal lumen was significantly increased in the control group and this increase was significantly inhibited in the rabeprazole treated group. Rabeprazole significantly reduces inflammation and hyperplasia in esophageal mucosa. These results indicate that bile acid, inhibited by rabeprazole, plays an important role in mucosal damage induced by duodenal reflux.

Effects of the Oil and Mucilage from Flaxseed (Linum Usitatissimum) on Gastric Lesions Induced by Ethanol in Rats

The anti-ulcer activity of the oil and mucilage obtained from flaxseed (Linum usitatissimum) was evaluated in a rat model of ethanol-induced gastric ulcer. Our results show that pretreatment of rats with flaxseed oil and flaxseed mucilage significantly reduced the number and length of gastric ulcers induced by ethanol. Flaxseed oil was more effective than flaxseed mucilage in reducing the number of ulcers. The reduction in ulcer severity (cumulative length in mm) provided by an oral dose of flaxseed oil (5 ml/kg) was more prominent than that obtained by ranitidine (50 mg/kg). This study indicates that both flaxseed oil and flaxseed mucilage can provide a cytoprotective effect against ethanol-induced gastric ulcers in rats.

Effects of the Oil and Mucilage from Flaxseed (Linum Usitatissimum) on Gastric Lesions Induced by Ethanol in Rats

The anti-ulcer activity of the oil and mucilage obtained from flaxseed (Linum usitatissimum) was evaluated in a rat model of ethanol-induced gastric ulcer. Our results show that pretreatment of rats with flaxseed oil and flaxseed mucilage significantly reduced the number and length of gastric ulcers induced by ethanol. Flaxseed oil was more effective than flaxseed mucilage in reducing the number of ulcers. The reduction in ulcer severity (cumulative length in mm) provided by an oral dose of flaxseed oil (5 ml/kg) was more prominent than that obtained by ranitidine (50 mg/kg). This study indicates that both flaxseed oil and flaxseed mucilage can provide a cytoprotective effect against ethanol-induced gastric ulcers in rats.

Inhibitory Effects of Fermented Brown Rice on Induction of Acute Colitis by Dextran Sulfate Sodium in Rats

Although the pathogenic mechanisms of inflammatory bowel diseases are not fully understood, colonic microbiota may affect the induction of colonic inflammation, and some probiotics and prebiotics have been reported to suppress colitis. The inhibitory effects of brown rice fermented by Aspergillus oryzae (FBRA), a fiber-rich food, on the induction of acute colitis by dextran sulfate sodium (DSS) were examined. Feeding a 5% and 10% FBRA-containing diet significantly decreased the ulcer and erosion area in the rat colon stained with Alcian blue. In another experiment, 10% FBRA feeding decreased the ulcer index (percentage of the total length of ulcers in the full length of the colon) and colitis score, which were determined by macroscopic observation. It also decreased myeloperoxidase activity in the colonic mucosa. Viable cell numbers of Lactobacillus in the feces decreased after DSS administration and was reversely correlated with severity of colitis, while the cell number of Enterobacteriaceae increased after DSS treatment and was positively correlated with colitis severity. These results indicate that FBRA has a suppressive effect on the induction of colitis by DSS and suggest FBRA-mediated modification of colonic microbiota.

5-Aminosalicylic Acid Improves Indomethacin-Induced Enteropathy by Inhibiting iNOS Transcription in Rats

Nitric oxide has been implicated in the pathogenic mechanism of inflammatory bowel disease states. We evaluated indomethacin-induced enteropathy in rats, in relation to the expression of the inducible isoform of NO synthase (iNOS) using aminosalicylic acid (5-ASA), its isomer 4-ASA (10 or 50 mg/kg/day, po), and dexamethasone, an iNOS transcription inhibitor (3 mg/kg/day, sc). Enteropathy was induced by indomethacin (7.5 mg/kg/day, sc) for two days and the small intestine was examined for lesions over the next 14 days. Indomethacin-induced small-intestinal ulcer size, mucosal myeloperoxidase activity, iNOS expression and serum nitrite/nitrate levels were maximally increased by day 4 and gradually decreased by day 14. Treatment with 5-ASA, but not 4-ASA, decreased indomethacin-induced ulcer length, myeloperoxidase activity, serum nitrite/nitrate levels and iNOS expression at day 4. Dexamethasone had a greater effect than 5-ASA in reducing myeloperoxidase activity and ulcer length by 26 and 32%, respectively. Dexamethasone also reduced serum nitrate/nitrite and iNOS expression to their basal levels. In conclusion, inhibition of iNOS expression by 5-ASA appears to be associated with diminished intestinal ulceration in indomethacin-induced enteropathy.

Hyperbaric Oxygenation Ameliorates Indomethacin-Induced Enteropathy in Rats by Modulating TNF-α and IL-1β Production

The effect of hyperbaric oxygenation (HBO2) was investigated in a rat model of indomethacin-induced enteropathy. Enteropathy was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) 24 hr apart. Six groups of rats (n=8) were treated with and without HBO2 (100% oxygen at 2.3 atm absolute) for 1 hr once or twice a day for 2 or 5 days. Disease activity index (DAI) and total ulcer length were measured. Other rats were randomized into two groups (n=16) with and without HBO2 (1 hr once a day) and four rats were killed in each group at 12, 24, 48, and 72 hr after the final injection of indomethacin. Serum and intestinal mucosal TNF-alpha, IL-1beta, myeloperoxidase (MPO), and iNOS expression was measured. HBO2 treatment significantly attenuated indomethacin -induced intestinal ulceration and improved DAI. Indomethacin increased MPO activity and iNOS expression, and these were reduced by HBO2 treatment, with a concomitant reduction in TNF-alpha and IL-1beta. Our data suggest that HBO2 treatment has a beneficial effect on indomethacin-induced enteropathy and this effect is possibly mediated by decreased production of TNF-alpha and IL-1beta.

Role of pancreatic trypsin in chronic esophagitis induced by gastroduodenal reflux in rats

Reflux of the duodenal contents with gastric acid has been reported to contribute to the development of esophageal mucosal damage and inflammation. Recent studies show that pancreatic trypsin can stimulate the production of inflammatory mediators, including chemokines and prostaglandins from human esophageal epithelial cells in vitro. The aim of the present study was to investigate the role of pancreatic trypsin in the pathogenesis of chronic esophageal inflammation induced by gastroduodenal reflux in rats. Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl ether inhalation anesthesia. The animals undergoing surgery were treated with the control diet, rabeprazole sodium, nizatidine, ecabet sodium, camostat mesilate (CMM), ONO-1714, a specific inducible nitric oxide synthase (iNOS) inhibitor, or meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor. Esophageal injury was evaluated by macroscopic and microscopic findings, and mRNA expression for CINC-1, COX-2, and iNOS was determined by real-time polymerase chain reaction (PCR). Trypsin activity within the esophageal lumen was measured 2 weeks after surgery, and the expression of protease-activated receptor (PAR)-1 and -2 was confirmed by reverse transcription (RT)-PCR. At 8 weeks after surgery, gastroduodenal reflux induced esophageal erosions and ulcer formation as well as marked thickening of the esophageal wall. Histological study showed an increase of thickness of the esophageal mucosa, hyperplasia of the epidermis and basal cells, ulcer formation, and marked infiltration of inflammatory cells. The macroscopic ulcer score and histological ulcer length were significantly reduced by treatment with rabeprazole or CMM but not by nizatidine or ecabet sodium, compared with each control. Rabeprazole, nizatidine, or ecabet sodium did not affect the severity of mucosal hyperplastic scores or histological parameters in esophagitis. In contrast, the CMM group showed a significant decrease in the mucosal hyperplastic and inflammatory scores. The enhanced expression of CINC-1, COX-2, and iNOS mRNA in the control group was also markedly inhibited in the CMM-treated group. ONO-1714 or meloxicam treatment significantly reduced the macroscopic scores of ulcer and hyperplasia. The trypsin activity in the esophageal lumen was significantly increased in the control diet group, and this increase was significantly inhibited in the CMM-treated group. The expression of PAR-1 and -2 mRNA was confirmed in rat esophageal epithelium. With this model, we have demonstrated that CMM significantly reduces inflammation and hyperplasia in the esophageal mucosa. These results indicate that trypsin, which is primarily inhibited by CMM, plays an important role in the mucosal damage induced by gastroduodenal reflux and that it can be a therapeutic target in patients with gastroduodenal reflux esophagitis.

Prognostic factors for venous ulcer healing in a non-selected population of ambulatory patients.

The rate of decrease in the length of venous ulcers can help identify people with a prognosis of poor healing. This study showed that a decrease of 40 per cent or more at four weeks was predictive of complete recovery at 12 to 24 weeks. Slow healing was associated with incorrect use of compression bandaging, older age and higher body mass index. There was also a correlation between high basal diastolic blood pressure and slow healing. This may have been an indication that these ulcers were not of purely venous origin. The authors believe that their research shows that leg ulcers rarely occur in isolation and often require broad management rather than just local treatment.

Prognostic factors for venous ulcer healing in a non-selected population of ambulatory patients

To identify wound prognostic indicators in a non-selected patient population with leg ulcers. This was a prospective observational survey involving 151 physicians. Ambulatory patients with venous leg ulcers were treated with a non-adherent foam dressing and usual leg ulcer management. At follow-up after three to six weeks, ulcer healing parameters and local treatment tolerability were recorded and concordance with compression therapy was validated. A > or = 40% reduction in the largest wound length was selected as an indicator of a favourable healing outcome. A total of 330 patients were included and seen at follow-up. The mean largest wound length was 4.9 +/- 3.6 cm. A > or = 40% decrease in this parameter was noted in 178 patients. Dressing acceptability and tolerability were excellent. Compression therapy, while heterogeneous among physicians, was used regularly and applied correctly (by patients and practitioners) in 81.2% of patients. Predictors for not reaching the main outcome were the presence of an arterial lower limb disease, an ulcer duration of more than three months and an initial ulcer length of 10 cm or more. Linear regression showed that old age and a high body mass index were independent predictors of a poor outcome. Clinical indicators such as simple ulcer length measurement and ulcer duration may help physicians to detect patients with a prognosis of poor healing.

Anti-ulcer and wound healing activity of Ruta graveolens

The effects of ethanol extract of Ruta graveolens on ulceration induced by ethanol and wound healing properties were investigated in mice. Oral administration of the extract reduced the incidence of ulcer, ulcer index and ulcer length produced by ethanol. The gastroprotective effects of R. graveolens were observed in a dose-dependent manner. However, this activity was statistically less potent than the anti-ulcer drug, omeprazole. When the extract applied on the wound, it promoted wound healing in mice. The wound contraction was faster in these mice when compared to untreated wounds. Based on these present findings, R. graveolens possesses anti-ulcer activity and promotes incision wound healing in mice.

Effect of thyroid hormones on stress ulcer formation.

Stress ulcers are gastric mucosal lesions that may cause life-threatening upper gastrointestinal bleeding. Although it is known that hyperthyroid status prevents stress ulcer formation, the effect of thyroid hormones given just as the stress is beginning has not been studied. The aim of this study was to assess the effect of thyroid hormone supplementation on gastric stress ulcers at the beginning of the restraint stress. Thyroid hormones were administered to rats 2 days before or at the beginning of the restraint stress. The linear length of the gastric mucosal lesions, mucosal pH and thyroid hormone levels were measured and histopathological examinations were carried out. It was found that both triiodothyronin and thyroxin reduce the length and depth of the stress ulcers (P < 0.001). Although the mechanisms by which the thyroid hormones act on stress ulcers are uncertain, current experimental studies suggest that thyroid hormones reduce the formation of stress ulcers in rats when given before or at the beginning of the stress.

New Rat Model for the Research of Stress Ulcer Accompanying Subarachnoid Hemorrhage

Background: Various rat models have been used to study subarachnoid hemorrhage related to a stress ulcer. However, these models have many problems such as high mortality, low success rates, and a bias due to a long procedure time. The purpose of this study was to develope a more reliable rat model for the study of subarachnoid hemorrhage related to a stress ulcer. Methods: Sprague-Dawley rats were anesthetized, and various volume of autologous blood were injected into the basal cistern by percutaneous injection. Mild stress consisting of restraint plus 4oC cold water immersion, 20oC cold water immersion, or 4o C cold water immersion with 40oC water rewarming were used to produce a stress ulcer. Thirty minutes after water immersion, rats were euthenized and the relative ulcer length (RUL) was measured. Results: Experimental subarachnoid hemorrhage by an injection of 0.2 ml autologous blood and three cycles of restraint plus 4oC cold water immersion with 40oC water rewarming produced a marked ulceration without mortality and a significant neurologic deficit. Conclusions: An injection of 0.2 ml autologous blood combined with three cycle of restraint plus 4oC cold water immersion with 40oC water rewarming is an ideal model to study subarachnoid hemorrhage related to a stress ulcer.

Nitric oxide inhibitors ameliorate indomethacin-induced enteropathy in rats.

The role of nitric oxide (NO) synthase inhibitors in indomethacin (INDO) -induced enteropathy was investigated in male Sprague-Dawley rats. Rats were subcutaneously administered 5% sodium bicarbonate (controls), two doses of INDO 7.5 mg/kg, and three different inducible NO synthase (iNOS) inhibitors at various concentrations 24 hr, apart; aminoguanidine (AG), guanidinoethyldisulfide (GED), and n-(3-aminomethyl)benzylacetamidine (1400W). Rats were killed four days after the initial injection and small intestinal mucosa was assayed for myeloperoxidase (MPO) activity and iNOS expression by western blot analysis. Serum nitrite/nitrate (NOx) concentration was measured colorimetrically. INDO produced acute ulcers along the mesenteric border from the ileum to proximal jejunum. Rats treated with AG (25 and 50 mg/kg), GED (2.5 mg/kg), and 1400W (0.1 mg/kg) showed decreased total ulcer length and MPO activity by 51, 72, 53, and 61% and by 58, 88, 68, and 70%, respectively, compared to INDO alone. All inhibitors similarly reduced INDO-enhanced serum NOx concentrations to its basal levels. Significant iNOS expression was detected in INDO-treated rats, but the inhibitors did not alter iNOS expression. Our data suggest that NO derived from iNOS may be a key factor in the pathogenesis of acute INDO-induced enteropathy in rats.