Degeneration Of Mucosa Research Articles

The Effect of Desloratadine Upon Ischemia-reperfusion-induced Oxidative and Inflammatory Gastric Injury in Rats

Background: Ischemia-reperfusion (I/R) injury is a pathological process mediated by oxidative stress and inflammation that begins with oxygen deprivation. This study, it was aimed to investigate the protective effect of desloratadine on gastric I/R damage in rats. Methods: Eighteen rats were randomly divided into 3 groups gastric I/R (GIR), gastric I/R + 5 mg/kg oral desloratadine (GIRD) and gastric sham operation (GSG). One hour later desloratadine administration, clips were placed in the celiac arteries of the rats in the GIRD and GIR groups. Ischemia was created by keeping the clips closed for one hour. Afterward, the clips were removed and reperfusion was achieved for three hours. The sham operation was performed on the GSG group. Then, all animals were euthanized with 120 mg/kg ketamine. Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD) catalase (CAT) and interleukin-6 (IL-6) levels were determined in the excised gastric tissues. All tissues were also analyzed histopathologically. Result: When the GIR group was compared with the GSG, an increase in MDA and IL-6 levels and a decrease in tGSH, SOD and CAT levels were observed (p less than 0.001). In addition, severe mucosal degeneration, congestion, polymorphonuclear leukocyte infiltration and mucosal edema were detected in the GIR group. Desloratine significantly inhibited both biochemical and histopathological changes (p less than 0.05).

Gastroprotective effect of <em>n</em>-butanol fractions from <em>Lumnitzera racemosa </em>leaves against indomethacin induced ulcer in Wistar rats

Phytoconstituents from plants serve as a safe replacement for synthetic molecules in drug production. Lumnitzera racemosa Willd., commonly called white-flowered black mangrove, is used in folk medicine to treat inflammation and other diseases. Here, we evaluated the antiulcer activity of two fractions (LR-B-4-11 and LR-B-4-12) of n-butanol (n-BuOH) fractions of L. racemosa leaves at the doses of 50 and 100 mg/kg, body wt. against indomethacin induced gastric mucosal injury in Wistar rats. The rats were dissected and their stomachs were inspected macroscopically to diagnose hemorrhagic lesions in the gastric and fundic mucosa. Administration of the fractions at doses of 50 and 100 mg/kg body wt., demonstrated a significant reduction in the indomethacin induced gastric erosion when compared to the control. The lower dose of LR-B-4-11 fraction (50 mg/kg) resulted in better inhibition of indomethacin induced gastric ulcer as compared to the control. Histological studies of the fundic and gastric mucosa reported that indomethacin led to mucosal degeneration, ulceration, and migration of numerous inflammatory cells throughout the section. On the other hand, pretreated groups with n-BuOH fractions demonstrated substantial regeneration of the mucosal layer and significant prevention of hemorrhage and edema occurrence

The ameliorative impacts of wheat germ oil against ethanol-induced gastric ulcers: involvement of anti-inflammatory, antiapoptotic, and antioxidant activities.

This study examined if wheat germ oil (WGO) has gastroprotective impacts against ethanol-induced gastric ulcer in rats. Rats were assigned into control, WGO, ethanol, omeprazole + ethanol, and WGO+ethanol. WGO prevented gastric ulceration and damage induced by ethanol, the same effect induced by omeprazole, a widely known medication used for gastric ulcer treatment. WGO reduced gastric ulcer index, nitric oxide, and malondialdehyde levels in the stomach. WGO boosted the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, and the antioxidants. WGO showed inflammatory and anti-inflammatory impacts through the control of interleukin (IL)-1β, Tumor necrosis factor alpha (TNF-α), and IL-10 that were altered in ethanol-administered rats. Ethanol up-regulated caspase-3 and nuclear factor-kappa B (NF-kB) expression and showed histopathological changes such as necrosis and mucosal degeneration that were mitigated by pre-administration of WGO. Moreover, WGO decreased gastric immunoreactivity of NF-kB and increased transforming growth factor beta-1 (TGF-β1) that were associated with upregulation of Nrf2, heme oxygenase-1 (HO-1), and antioxidant expression and production. In conclusion, WGO reduced ethanol-induced stomach toxicity by regulating genes involved in oxidative stress, inflammation, and apoptotic/antiapoptotic pathways.

Risk stratification of anastomotic stricture using early postoperative endoscopic and computed tomography findings in patients undergoing esophagectomy with cervical esophagogastric anastomosis for esophageal cancer.

Anastomotic stricture (AS) is one of the major complications after esophagectomy for esophageal cancer. We have previously reported that severe mucosal degeneration (MD) of the anastomotic site was associated with the incidence of AS. Meanwhile, there are few reports to correlate anastomotic internal circumference (AIC) with computed tomography (CT) with the incidence of AS. Therefore, this study was conducted to clarify the correlation of early postoperative endoscopic and CT findings with the incidence of AS. We assessed 205 patients who underwent esophagectomy. We then divided them into the non-AS group (n = 164) and the AS group (n = 41) and compared their background data and intraoperative and postoperative outcomes. We also evaluated the risk factors for AS using logistic regression model. Multivariate analysis revealed small AIC (P = 0.003; OR = 4.400; 95% CI = 1.650-11.700) and severe MD (P < 0.001; OR = 7.200; 95% CI = 2.650-19.600) as the independent risk factors for AS development. We also stratified the patients into the following four groups according to the incidence of AS: low-risk (normal AIC and intact or mild MD, 6.2%), intermediate-risk (small AIC and intact or mild MD, 29.4%), high-risk (normal AIC and severe MD, 42.9%), and very high-risk (small AIC and severe MD, 61.1%). Early postoperative endoscopic and CT findings were useful in predicting the development of AS after esophagectomy.

Wheat oligopeptides enhance the intestinal mucosal barrier and alleviate inflammation via the TLR4/Myd88/MAPK signaling pathway in aged mice.

BackgroundAging can induce oxidative stress, inflammation and mucosal impairment, and few works have been conducted to investigate the protective effects of WP on the natural intestinal aging process.ObjectiveThe present work aimed to examine the protective effect of wheat oligopeptides (WP) on intestine mucosal impairment in aged mice, and investigate the potential antioxidation, anti-inflammatory effects of WP.DesignSeventy-two aged mice (24 months old) were randomly divided into six groups, 12 for each group. Twelve young mice (6 months old) were regarded as the young control group. WP (25, 50, 100, 200, or 400 mg/kg) or distilled water were administered daily by gavage for 30 days.ResultsHistological observations showed that intestinal mucosal degeneration was attenuated by WP pretreatment. WP exhibited remarkable antioxidant activity via increasing superoxide dismutase, glutathione peroxidase, total antioxidant capacity and catalase activities, and decreasing the malondialdehyde levels in small intestine mucosa. WP pretreatment significantly suppressed intestinal mucosa inflammation through the reduction of TNF-α, TGF-β, IFN-γ IL-1β and IL-6. WP markedly protect the intestinal mucosal barrier by decreasing the ICAM-1 level, and increasing ZO-1 and JAMA-A levels. WP significantly down-regulated protein expression levels of TLR4, Myd88, and MAPK, suggesting that WP have a potential effect on inhibiting aging-induced inflammatory responses by blocking TLR4/Myd88/MAPK signal transduction.ConclusionWP administration effectively alleviated intestinal mucosal impairment in aged mice. The potential mechanism was associated with enhancement of antioxidation and anti-inflammatory action and protection of the intestinal mucosal barrier.

Role of Semisulcospira gottschei extract as medicinal food on reflux esophagitis in rats.

Gastroesophageal reflux disease (GERD) is a globally prevalent disease and results from a reflux of gastric contents into the esophagus. Existing synthetic drug‐based treatments for GERD have various drawbacks including refractory symptoms, relapse, or resistance due to long‐term use or may result in mucosal degeneration, polyps, and osteoporosis. Semisulcospira gottschei (SE), a freshwater snail, has been generally consumed as a food source due to its excellent flavor and nutritional value in Korea and considered to have therapeutic properties for various diseases including dyspepsia, stomachache, and hepatic diseases. The present study aims to investigate whether Semisulcospira gottschei extract (SGE) has a protective effect on reflux esophagitis‐induced rat models. The anti‐inflammatory effects of SGE were evaluated via NO production in LPS‐induced Raw 264.7 macrophage. And the protection effects of SGE were analyzed by assessing the amelioration of mucosal damage and expression of inflammation‐associated proteins in reflux esophagitis (RE) rats. Our results indicate that SGE significantly suppressed NO production in LPS‐induced raw 264.7 cells without any cytotoxicity. We observed mucosal lesions and histological changes in the esophagus of RE control rats. However, SGE treatment markedly ameliorated mucosal lesion ratio indicated through histological changes. SGE administration suppressed the expression of proteins related to inflammation, such as p‐NF‐κB, p‐IκBα, COX‐2, and TNF‐α, in esophageal tissue. Moreover, SGE elevated the expression of claudin‐5, which is a tight junction protein, involved in barrier function of epithelium and endothelium. The results suggest that SGE is useful as a medicinal food in esophagitis and may be helpful in developing effective treatment protocols for GERD.

IL-8 and LYPD8 expression levels are associated with the inflammatory response in the colon of patients with ulcerative colitis.

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder affecting the large intestine, which may involve mucosal degeneration. Glycoproteins, mucin2 (MUC2) and the LY6/PLAUR domain containing 8 (LYPD8) are present on the mucous layer of the colon and can hinder the invasion of bacteria, thus contributing to the prevention of colitis. The present study investigated the expression levels of interleukin-8 (IL-8), MUC2 and LYPD8 on the mucous membranes of patients with UC. A total of 18 patients with UC (6 females and 12 males) were examined. Biopsies of the lesions as well as matching normal membranes were obtained and the mRNA expression levels of IL-8, MUC2 and LYPD8 were compared. LYPD8 expression was downregulated in the lesions and the relapsing-remitting subtype of lesions was associated with higher levels of MUC2 expression compared with single attack and chronic lesions subtypes. A positive correlation between Matts' histopathological grade and IL-8, as well as a negative correlation between Matts' histopathological grade and LYPD8 were observed. The expression levels of LYPD8 were lower in highly active lesions and these levels decreased according to the intensity of the mucosal inflammation. Conversely, an increase in MUC2 expression levels may reflect the recovery of the outer mucus layer in the remission phase. Therefore, the examination of MUC2 and LYPD8 expression levels may be useful indicators of mucosal healing in patients with UC.

Acute Oral Toxicity of Pinnatoxin G in Mice.

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg−1). At the dose of 220 µg kg−1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg−1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 μg kg−1 (95% confidence limits: 155–281 µg kg−1) and to estimate a provisional NOEL of 120 µg kg−1.

Two cases of esophageal ulcer after surgical treatment for ulcerative colitis.

The incidence of postoperative esophageal ulcers has been rarely reported associated with severe ulcerative colitis (UC). We report two cases of esophageal ulcers accompanied by acute necrotizing esophagitis after undergoing surgery for severe UC. Both patients, 47- and 53-year-old, were diagnosed with severe UC and underwent subtotal colectomy with sigmoid mucous fistula and ileostomy. In both cases, they had epigastralgia or digestive track bleeding and upper gastrointestinal endoscopy revealed an esophageal ulcer with acute necrotizing esophagitis accompanied by a black degeneration of mucosa after surgery. Conservative treatments improved the lesions. Esophageal stricture requiring endoscopic dilatation occurred in both cases. An acute UC requiring surgery seems to warrant caution in the merger of esophageal ulcer and acute necrotizing esophagitis.

Early prediction of complex benign anastomotic stricture after esophagectomy using early postoperative endoscopic findings.

Benign anastomotic stricture after esophagectomy and reconstruction adversely affects oral intake and can increase the risk of aspiration pneumonia. Some patients experience relapse that requires frequent endoscopic dilatations. This study aimed to investigate whether the endoscopic appearance of anastomosis during the early postoperative period is associated with the complexity of subsequent anastomotic strictures. Data of 213 patients who underwent esophagectomy with gastric tube reconstruction and early postoperative endoscopy between July 2008 and September 2018 were prospectively collected. Relationships among various risk factors, including the severity of mucosal degeneration of the anastomosis and complexity of anastomotic stricture, were studied using multivariate logistic regression analysis. Fifty-three patients (25%) developed anastomotic strictures at a median of 55days after surgery, requiring a median of 5 endoscopic dilations. In multivariate analysis, severe mucosal degeneration was the only significant risk factor for any type of anastomotic stricture (P < 0.001). Twenty-seven patients (51%) developed refractory anastomotic strictures. In multivariate analysis, younger age (< 65years) (P = 0.01), lack of neoadjuvant therapy (P = 0.02), severe mucosal degeneration (P = 0.03), and stricture development within 55days (P = 0.01) were the risk factors for refractory stricture. The analysis of the risk factors for severe mucosal degeneration revealed that comorbidities and anastomotic techniques were independently correlated (P < 0.01). Early postoperative severe mucosal degeneration of esophagogastrostomy was the only predictor of strictures, regardless of their type. Mucosal degeneration, early postoperative stricture, younger age, and front surgery were associated with refractory anastomotic strictures.

Partially hydrolyzed guar gum alleviates small intestinal mucosal damage after massive small bowel resection along with changes in the intestinal microbiota

PurposeShort bowel syndrome is associated with intestinal mucosal inflammation and microbial dysbiosis, leading to intractable complications. Partially hydrolyzed guar gum (PHGG) has trophic and anti-inflammatory effects on the intestine. We investigated whether PHGG ameliorates small intestinal mucosal damage and alters the intestinal microbiota using a rat small bowel resection (SBR) model. MethodsSprague Dawley rats were divided into sham operation (Sham), Sham/PHGG, SBR, and SBR/PHGG groups. On day 21, all rats were euthanized. To assess small intestinal mucosal damage, the degeneration rate was morphometrically evaluated and immunohistochemically examined using anti-CD45 antibodies. Analyses of fecal microbiota using 16S rRNA and short-chain fatty acid production were also performed. ResultsThe mucosal degeneration rate was significantly higher in the SBR group than in the Sham or SBR/PHGG groups. The number of CD45-positive cells was significantly higher in the SBR group than in the Sham, Sham/PHGG, or SBR/PHGG groups. The relative abundance of family Lachnospiraceae was significantly higher in the SBR/PHGG group than in the SBR group. ConclusionsPHGG administration alleviated small intestinal mucosal damage which could be associated with modulation of the intestinal microbiota.

Calcineurin B1 Deficiency in Glial Cells Reduces Gastrointestinal Motility and Results in Maldigestion and/or Malabsorption in Mice.

Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase abundantly expressed in the nervous system. To investigate the roles of calcineurin in glial cells, we previously generated glial calcineurin B1-conditional knockout (CKO) mice and found that these mice displayed dysfunction of enteric glial cells, mucosal degeneration and inflammation in the small intestine, and growth retardation and postweaning death, suggesting a novel role of calcineurin in enteric glial cells. Although these findings raised a possibility that abnormalities in calcineurin B1-deficient enteric glial cells may cause dysregulation of gastrointestinal motility and result in maldigestion and/or malabsorption in the CKO mice, these issues remain to be elucidated. In the present study, we showed that gastrointestinal motility was reduced in the CKO mice. Degeneration of mucosal epithelium was observed in the small intestine. Glucose levels were decreased in serum, whereas starch, glucose, and lipid levels were increased in feces. Thus, calcineurin B1 deficiency in glial cells reduces gastrointestinal motility, induces mucosal epithelium degeneration in the small intestine, and results in maldigestion and/or malabsorption in mice, further supporting the important role of calcineurin in enteric glial cells.

Beneficial effects of vitamin E on radioiodine induced gastrointestinal damage: an experimental and pathomorphological study.

The aim of the present study was to investigate the radioprotective effect of vitamin E in the prevention of radioiodine (RAI) induced gastrointestinal damage. Twenty-four rats were randomly divided into three groups as follows: Group-1 was untreated control group, Group-2 was orally administered single dose of 111 MBq RAI, and Group-3 was orally administered 111 MBq RAI and 1 mL of oral vitamin E. Vitamin E was started two days before RAI administration and was continued for five days once daily after RAI. Pathomorphological parameters of gastrointestinal tissues (stomach, small intestines and bowels) were measured using Hematoxylin-Eosin and Masson's trichrome staining. Varying degrees of inflammation, edema, ulcer, mucosal degeneration, necrosis and fibrosis were seen in the stomach, small intestine and bowel tissues of the rats in both study groups and not in the control group. The differences were statistically significant between these groups for all parameters (p < 0.05). The histopathological damage in the vitamin E treated group was significantly less than the damage in the RAI only group (p < 0.05 for all pathomorphological parameters). The results of this study showed that vitamin E has a radioprotective property with antiinflammatory and antifibrotic effects protecting against gastrointestinal damage caused by radioiodine (Tab. 3, Fig. 3, Ref. 26).

Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABAARs in the Hippocampus in Early Postnatal Sprague Dawley Rats.

Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5μl) or saline (sham, 5μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n = 6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P < 0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P < 0.01) and increased levels of learned helplessness (P < 0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABAA receptor alpha5 subunit (α5GABAAR) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P < 0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.

Modest Static Pressure Suppresses Columnar Epithelial Cell Growth in Association with Cell Shape and Cytoskeletal Modifications.

Intraluminal pressure elevation can cause degenerative disorders, such as ileus and hydronephrosis, and the threshold is fairly low and constant, 20–30 cm H2O. We previously devised a novel two-chamber culture system subjecting cells cultured on a semipermeable membrane to increased culture medium height (water pressure up to 60 cm H2O). Here, we sought to determine how a continuous pressure load of ~30 cm H2O affects proliferating epithelial cells with special interest in the link with cell morphology. We cultured several different cell lines using the low static pressure-loadable two-chamber system, and examined cell growth, cell cycle, and cell morphology. Madin–Darby canine kidney (MDCK) columnar epithelial cells were growth-suppressed in a manner dependent on static water pressure ranging from 2 to 50 cm H2O, without cell cycle arrest at any specific phase. Two other types of columnar epithelial cells exhibited similar phenotypes. By contrast, spherical epithelial and mesenchymal cells were not growth-suppressed, even at 50 cm H2O. Phalloidin staining revealed that 50 cm H2O pressure load vertically flattened and laterally widened columnar epithelial cells and made actin fiber distribution sparse, without affecting total phalloidin intensity per cell. When the mucosal protectant irsogladine maleate (100 nM) was added to 50-cm-high culture medium, MDCK cells were reduced in volume and their doubling time shortened. Cell proliferation and morphology are known to be regulated by the Hippo signaling pathway. A pressure load of 50 cm H2O enhanced serine-127 phosphorylation and cytoplasmic retention of YAP, the major constituent of this pathway, suggesting that Hippo pathway was involved in the pressure-induced cell growth suppression. RNA sequencing of MDCK cells showed that a 50 cm H2O pressure load upregulated keratin 14, an intermediate filament, 12-fold. This upregulation was confirmed at the protein level by immunofluorescence, suggesting a role in cytoskeletal reinforcement. These results provide evidence that cell morphology and the cytoskeleton are closely linked to cell growth. Pathological intraluminal pressure elevation may cause mucosal degeneration by acting directly on this linkage and the Hippo pathway.

Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis

Background and aimInflammatory bowel disease (IBD) is an autoimmune-inflammatory disorder that results in inflammatory responses in individuals who are genetically susceptible. Uncontrolled inflammation in Crohn's disease (CD) or Ulcerative colitis (UC) affects the patient quality of life. Current therapies are not completely effective while cell therapy, especially the treatment with mesenchymal stem cells (MSCs) absorb lots of attention due to its immunomodulatory properties. So, we examined the effects of mesenchymal stem cells-conditioned medium (MSC-CM) in the experimental model of acute colitis. Material and methodMSC-CM was isolated from C57Bl/6 male mice and stored. The acute colitis induction in C57BL/6 mice was performed by dissolving dextran sulfate sodium (DSS) in drinking water and then CM injected intraperitoneally. During the study body weight changes, bleeding, stool consistency, disease activity index (DAI), mortality rate, weight and length of the colon and histopathological analysis were recorded as well as changes in the percentage of Treg cells. The level of IL-17, IL-10, and TGF-β were measured, too. Data were reported as mean±SD and analyzed by One-Way ANOVA test. ResultsBased on the results it is recognized CM inhibited the weight loss and bleeding and improved fecal consistency and DAI. Macroscopic examination of the colon showed that after infusion, colon inflammation was reduced and histopathological analysis showed a decrease in mucosal degeneration. The percentage of Treg cells, secretion of IL-10 and TGF-β was increased while the IL-17 level was reduced. ConclusionThis study showed that mesenchymal stem cell secretion with immunomodulatory properties has the potential to reduce inflammatory responses.

Impact of Mucosal Degeneration of Gastric Conduit on Refractory Anastomotic Stricture after Esophagectomy

Impact of Mucosal Degeneration of Gastric Conduit on Refractory Anastomotic Stricture after Esophagectomy

Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats

BackgroundThe medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity.MethodsThe anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa.ResultsP. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract’s doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema.ConclusionsThe investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

Early postoperative endoscopy for targeted management of patients at risks of anastomotic complications after esophagectomy

Early postoperative endoscopy after esophagectomy is assumed to be effective in detection and prediction of anastomotic complications, but overall effects of early postoperative endoscopy remain uncertain. The aim of this study was to investigate whether mucosal status assessed by early postoperative endoscopy could offer an approach to individualized management after esophagectomy. Endoscopy was performed in 176 of 214 patients who underwent esophagectomy at either 1week or 2weeks postoperatively. Mucosal damage in the proximal region of the graft was classified as follows: intact mucosa, mild mucosal degeneration, and severe mucosal degeneration. We examined the association of the severity of mucosal damage and the incidence of anastomotic complications. Twenty-eight patients (16%) developed anastomotic stricture. Symptomatic anastomotic leaks occurred in 15 patients (8.5%), including 6 with stricture. The frequency of intact mucosa, mild mucosal degeneration, and severe mucosal was 7%, 20%, and 73% for leaks; 4%, 11%, and 85% for strictures; and 28%, 62%, and 10% for no complications, respectively (P <.001). Asymptomatic leaks were found in 4 patients in the 1-week endoscopy group. Sensitivity and specificity for the development of stricture in 1-week/2-week were 0.88/0.83 and 0.85/0.98, respectively. Positive and negative predictive values were 0.52/0.91 and 0.97/0.96, respectively. Early postoperative endoscopy could be carried out without any adverse events in all patients. Assessment of the anastomosis and graft with early postoperative endoscopy was safe and resulted in a high predictive value for subsequent anastomotic complications. Early postoperative endoscopy may lead to targeted management for a subset of patients undergoing esophagectomy.