Severity Of Mucosal Lesions Research Articles

Evaluation of desmoglein 1 and 3 autoantibodies in pemphigus vulgaris: correlation with disease severity.

BackgroundPemphigus is an autoimmune blistering disease of the skin and mucous membranes caused by autoantibodies against desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). Pemphigus vulgaris (PV) is the most common form of pemphigus. The aim of this study was to assess the correlation between the levels of anti-desmoglein 1 and 3 autoantibodies and the severity of PV disease. Material and MethodsNineteen newly diagnosed patients with pemphigus vulgaris were enrolled in this study. The titers of Dsg in subjects by using enzyme-linked immunosorbent assay (ELISA) were done at diagnosis time-point, 4th and 8th weeks after the initiation of treatment, and the correlation of antibodies with the oral and skin disease severity was evaluated. ResultsThe severity of cutaneous lesions was significantly correlated with anti-Dsg1 titer in all visits and the severity of mucosal lesions was correlated with the titer of Dsg3 in the third visit (<0.001, 0.001, 0.016 and 0.015 P value, respectively). ConclusionsAnti-Dsg-1 autoantibodies titers seem to be more useful in showing the extent of the disease and activity in pemphigus with mucocutaneous lesions. Key words:Pemphigus vulgaris, Desmoglein (Dsg), Enzyme-linked immunosorbent assay (ELISA).

THE STATE OF THE MUCOSA OF THE GASTRODUODENAL ZONE IN SCHOOLCHILDREN RESIDING IN AREAS WITH A HIGH PREVALENCE RATE OF GASTRIC CANCER

The aim is to determine the severity of mucosal lesions of gastroduodenal zone, colonization of Helicobacter pylori and their association with intestinal complaints by school students of the aboriginal and alien population of the Republic of Tuva. Materials and methods. Over 2017 we had observed 471 schoolchildren aged 7-17 years from the aboriginal (Tuva-Mongoloids) and aliens (Caucasians) population of the Republic of Tuva. We created represented groups (69 aboriginal and 34 alien inhabitants) and executed esophagogastroduodenoscopy with the biopsy from the antrum and body of stomach taken from each examinee. Diagnosis of gastritis was made in accordance with Sydney classification. H. pylori was determined by the morphological method. Results. The H. pylori infection in Tuvans (68,4%) was higher than in Caucasians (376%; p = 0,0047). Erosive and ulcerative lesions of the stomach and duodenum were detected in 15.5% of patients and they were diagnosed among Caucasians twice often than among Tuvinians (23,5% and 11,6%, respectively; p = 0,1158). The relation between infection and the presence of the erosive and ulcerative process of the gastric mucosa in children has not been established. The predominance of the activity of antral gastritis in his relation with infection H. pylori (p = 0,0009) and bacterial content of H. pylori in the mucosa of the stomach had been marked in Tuvinians in comparison with Caucasians. These indices in Tuvinians were associated with the metaplasticity process. Conclusion. Tuvinians schoolchildren in the Republic of Tuva have higher H. pylori infection rate. H. pylori-associated gastritis has a more progressive course in aboriginal children. The authors believe an evaluation of the course of the pathological process in Tuvan children can be the basis for creating eradication therapy programs for indigenous children in the Republic of Tuva, which must take into account the regional specificity of the diseases associated with H. pylori in order to prevent precancerous changes.

Methylene Blue Protects against Acidified Sodium Taurocholate-Induced Gastric Mucosal Damage

The effect of methylene blue (MethyB) on the development of gastric mucosal injury caused by orally given acidified sodium taurocholate (80 mM in 2 ml of 0.15 N HCI) in pylorus-ligated rats was studied. MethyB was intraperitoneally given at doses of 20 and 40 mg/kg at time of pylorus-ligation, and animals were euthanized 90 min later, when gastric secretory responses and the number and severity of mucosal lesions were determined. Lipid peroxidation (malondialdehyde), nitric oxide, reduced glutathione (GSH), and paraoxonase-1 (PON-1) activity in gastric homogenates were measured. Gastric mucosal histopathology and histochemical staining for mucopolysaccharides were also done. Results indicated that acidified sodium taurocholate (Na+-taurocholate) caused severe gastric lesions. It also increased gastric malondialdehyde by 70% and decreased GSH levels by 36.4% compared with the corresponding control values. Additionally, nitric oxide decreased by 49.3% and PON-1 activity fell by 54.2% in gastric tissue of Na+-taurocholate-treated rats. The administration of MethyB reduced the number and severity of gastric mucosal lesions but had no effect on gastric acid secretion in Na+-taurocholate-treated rats. MethyB resulted in decreased malondialdehyde and increased GSH, nitric oxide, and PON-1 activity in a dose-dependent manner. Na+-taurocholate caused massive sloughing and hemorrhagic erosions of the superficial parts of gastric epithelium, lamina propria, and sloughing of gastric glands. These changes were markedly attenuated by MethyB at 40 mg/kg. MethyB also restored gastric mucus as indicated by the increase in apical epithelial cells positively stained with periodic acid Schiff. These data suggest a protective effect for MethyB against gastric mucosal damage caused by Na+-taurocholate which is likely to be due to decreased oxidative stress.

Recurrent Oral Ulcers: current and future therapeutic approaches

Recurrent Oral Ulcers: current and future therapeutic approaches

Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum.

Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

Clinical features of celiac disease: a prospective birth cohort.

To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children.

HEPATOPROTECTIVE AND GASTRO PROTECTIVE STUDIES OF Terminalia arjuna LEAVES EXTRACT AND PHYTOCHEMICAL PROFILE

The methanol extract of T. arjuna leaves was evaluated as hepatoprotective and gastroprotective against Swiss albino rats. In hepatoprotective study the liver damage induced by paracetamol while the gastric lesion induced by absolute ethanol in the gastro protective study. The extract was given orally (250,500 and 1000 mg/kg) in different experimental models in both studies. The extract at dose (500mg/kg) showed significant reduction in ALT serum level by 19.9% while at dose (1000mg/kg) it reduced significantly serum ALT, AST and ALP levels by –26.15,–25.46 and – 23.69 % respectively as compared with paracetamol treated group. In the gastro protective study the extract produced significant reduction in the number and severity of mucosal lesion by (–52.1 &–67.3 %, –66.7 &–71.2 % and –68.8 &–77.6%) respectively.

Role of bowel ultrasound in the management of postoperative Crohn's disease.

The use of biological and immunosuppressive therapy in Crohn's disease (CD) changed favorably the course of the disease and is currently suggested in the prevention of clinical recurrence. Symptomatic exacerbation is a feature of the natural course of the disease. Endoscopic recurrence may occur earlier than clinical manifestations and its rate is still high ever since the first year after surgery. The severity of mucosal lesions is highly predictive of a new flare of the disease so that the early detection of recurrence warrants strong therapeutic changes or a closer monitoring of the case. Endoscopy is at present the gold-standard technique for the diagnosis and grading of recurrence severity, but is poorly accepted by patients for its invasiveness. A simple and easy repeatable examination able to detect early signs of recurrence could be useful in the follow-up as an alternative or as a backing in the choice of the right timing for endoscopy in questionable cases. The use of bowel ultrasound (B-US) in the management of CD has grown in the past twenty years. Its accuracy in the real time detection of the disease and its complications, known since the 80's, together with the non-invasiveness, low cost and wide availability of the technique have influenced the extension of its clinical use in many referral centers in Europe. The latest generation of ultrasound scanners allows a precise and reproducible morphological assessment of the intestinal tract and the surrounding tissues and enables a complete evaluation of the disease. This review analyzes the literature history about B-US in the diagnosis of postoperative recurrence of CD and outlines the clinical implications of its use. Published works confirm a very good accuracy of B-US in the diagnosis of CD recurrence compared to endoscopy, also in the early phase. B-US shows a good correlation with Rutgeert's score grading, but does not prove significant association with C-reactive protein or CD Activity Index values. A wider use of B-US in the daily practice could allow to set a prompt diagnosis and an earlier and targeted treatment, probably sparing more invasive tests.

Chemical constituents and anti‐ulcerogenic potential of the scales of Cynara scolymus (artichoke) heads

Cynara scolymus L. (Asteraseae) (artichoke) is commonly eaten as a vegetable; its leaves are frequently used in folk medicine in the treatment of hepatitis, hyperlipidaemia, obesity and dyspeptic disorders. The purpose of this study is to determine the chemical composition of the volatile oil and alcoholic extract of artichoke head scales. In addition, the role of the methanol extract as an anti-ulcer agent against ethanol-induced gastric ulcer in rats was evaluated. Six flavonoids and one phenolic acid were obtained from the methanol extract. Also, 37 compounds were identified in the volatile oil, the majority including mono- and sesquiterpenes. The artichoke extracts (200 and 400 mg kg(-1)) significantly (P < 0.05) reduced the ulcer index (55.33% and 72.14% inhibition). Histopathological examination of rat stomachs demonstrated that artichoke induced an increase in gastric mucus production, and a reduction of the depth and severity of mucosal lesions. Artichoke dose-dependently reduced the elevated ethanol gastric malonylaldehyde, and reduced glutathione levels and catalase activity. These results suggest that the head scales of artichoke possess potential anti-ulcer activity. The present paper describes the identification of volatile oil for the first time along with the isolation and identification of the constituents of the methanol extract. Moreover, the high anti-ulcerogenic potential of scales of C. scolymus heads was established here for the first time.

Celiac Disease With Mild Enteropathy Is Not Mild Disease

Patients with celiac disease have varying degrees of damage to the small intestinal mucosa, ranging from lymphocytic duodenosis with normal villous structure to severe villous atrophy. We assessed whether the severity of mucosal lesions was associated with clinical and laboratory features of celiac disease. We compared demographic, clinical, and laboratory characteristics among patients with celiac disease who were classified based on the severity of duodenal lesions. We analyzed data from 1408 adult patients seen consecutively at a tertiary referral center since 1990. Patients were classified as having villous atrophy (n = 1249) or as having mild enteropathy (n = 159) in the presence or absence of villous atrophy. Similar percentages of patients with villous atrophy, vs mild enteropathy, experienced weight loss (17% vs 17%), gastrointestinal manifestations (70% vs 70%), extraintestinal manifestations (66% vs 57%), and other associated conditions (19% vs 23%). More patients with villous atrophy than patients with mild enteropathy developed osteopenia or osteoporosis (22% vs 5%; P = .0005). Greater percentages of patients with villous atrophy than those with mild enteropathy also had anemia (42% vs 29%; P = .002), folate deficiency (75% vs 64%; P = .02), hypocholesterolemia (7% vs 2%; P = .02), hypocalcemia (26% vs 13%; P = .004), or hyperparathyroidism (45% vs 29%; P = .004). Although osteopenia, osteoporosis, and alterations in laboratory parameters are prevalent among patients with celiac disease with mild enteropathy, they are more prevalent and severe in those with villous atrophy. The prevalence of associated conditions is similar between these groups. These results indicate that celiac disease with mild enteropathy is not mild disease, but requires treatment with a gluten-free diet.

Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis

This review addresses the question of whether the risk of developing mucosal leishmaniasis (ML) warrants systemic treatment in all patients with New World cutaneous leishmaniasis (CL) or whether local treatment might be an acceptable alternative. The risk of patients with New World CL developing ML after the initial infection has been the main argument for systemic treatment. However, this statement needs re-evaluation and consideration of all the available data. The putative benefit of preventing ML should outweigh the toxicity of systemic antileishmanial therapy. To assess the need for and risk of systemic treatment the following factors were reviewed: the incidence and prevalence of ML in endemic populations and in travellers; the severity of mucosal lesions; the efficacy of current options to treat ML; the toxicity and, to a lesser extent, the costs of systemic treatment; the risk of developing ML after local treatment; and the strengths and limitations of current estimates of the risk of developing ML in different situations. Local treatment might be considered as a valuable treatment option for travellers suffering from New World CL, provided that there are no risk factors for developing ML such as multiple lesions, big lesions (>4 cm(2)), localisation of the lesion on the head or neck, immunosuppression or acquisition of infection in the high Andean countries, notably Bolivia.

Oral mucosal lesions during orthodontic treatment

Oral mucosal lesions can result from irritation caused by orthodontic appliances or malocclusion, but their frequency is not known. To examine the frequency of oral mucosal lesions in wearers of orthodontic appliances in comparison to children with malocclusion. This study comprised 111 subjects: 60 wearers of orthodontic appliances and 51 controls (aged between 6 and 18 years). Type and severity of mucosal lesions, their topography, gingival inflammation, and oral hygiene status were determined by using clinical indices. Mucosal lesions were more present in wearers of orthodontic appliances than in children with malocclusion. Gingival inflammation, erosion, ulceration, and contusion were the most common findings in orthodontic patients. The severity of gingival inflammation was in correlation with oral hygiene status; the poorer oral hygiene, the more severe gingival inflammation was. Better oral hygiene status was found in children during orthodontic treatment than in children with malocclusion. Orthodontic treatment carries a higher risk of mucosal lesions and implies greater awareness of better oral hygiene as shown by the results of this study. Oral hygiene instructions and early treatment of oral lesions are important considerations in better patient's motivation, treatment planning, and successful outcome.

T2016 Novel Integration of Video and pH/Impedance Recording Coupled with Cardiorespiratory Monitoring for Evaluation of Pediatric Gastroesophageal Reflux Disease

for diagnostic work-up in a usual clinical care setting and the clinical predictors of response/ non-response. This abstract summarizes the interim analysis after recruitment of 100 patients. METHODS: One hundred patients referred for endoscopic assessment of suspected GERD within a single metropolitan area health service were recruited; 82 consecutive patients from the Royal Adelaide Hospital (RAH) and 28 from the Lyell McEwen Health Centre (LMH). Symptoms and psychological co-morbidities were assessed utilizing the Bowel Disease Questionnaire, the Hospital Anxiety and Depression Scale and the Nepean Dyspepsia Index. Questionnaires were mailed to the patients. Data on endoscopic findings at referral using the Los Angeles (LA) classification were included. As this was an observational study, routine clinical management by the referring GP was not altered. RESULTS: 68 patients were on proton pump inhibitor (PPI) therapy while 31 patients did not receive the treatment. In 58 patients endoscopy revealed no visible esophagitis. The frequency of heartburn was significantly associated with the presence of hiatal hernia but the frequency of reflux symptoms was not linked to the presence or severity of endoscopic lesions. Follow-up data > 2 month were available for 38 patients. Out of these 86.8% continued to have heartburn and 76.3% an acid taste after more than 2 months of treatment. The symptomatic response to PPI was significantly better (p 0.05). 36% of patients reported a history of anxiety and depression but these disorders were not correlated with symptom frequency or response to PPI therapy. CONCLUSIONS: a) Frequency of GERD symptoms is not associated with severity of mucosal lesions; b) presence of a hiatal hernia is linked to more frequent symptoms; c) presence of a hiatal hernia predicts a favourable response to PPI therapy.

T2015 Multivariate Analysis of Predictors for Severity of Mucosal Lesions in Patients with GERD Symptoms (Mapsomal): A Clinical, Epidemiological and Endoscopic Survey

T2015 Multivariate Analysis of Predictors for Severity of Mucosal Lesions in Patients with GERD Symptoms (Mapsomal): A Clinical, Epidemiological and Endoscopic Survey

Translational inhibition of epithelial Hsp70 by pro-inflammatory cytokines through 3′UTR and microRNAs in intestinal inflammation

Heat shock protein 70 (Hsp70) confers cytoprotection to cells under stress or injury and is highly expressed by colonic epithelial cells in direct contact with luminal fluid and flora. In both IBD and experimental colitis, Hsp70 expression is selectively decreased by the inflammatory agents IFN-γ and TNF-α, an effect that renders the mucosa more susceptible to immune and inflammatory stress. In this study, we are trying to clarify the mechanisms and mediators underlying this phenomenon. Hsp70 expression and regulation were assessed in colon tissue and YAMC colonic epithelial cells by immunohistochemistry, Western blot and real-time PCR. To determine the mediators involved in the translational regulation, a luciferase reporter assay, using pGL3 vectors integrated with Hsp70 3′UTR, was performed and a-UTR-less Hsp70 transgenic mouse was made, which express high level of Hsp70 in intestine. Hsp70 expression was also measured in an experimental colitis model (DSS-induced) in both wild-type and transgenic mice. To further investigate the regulators affecting the Hsp70 3′UTR, microRNAs, which have been reported to selectively bind to 3′UTRs and inhibit translation, were measured. We found IFN-γ and TNF-α inhibited Hsp70 induction both in vivo and in vitro. This effect did not associate with changes in Hsp70 mRNA or protein half-lives, but was the result of suppressed de novo Hsp70 synthesis, which indicates translational regulation. The luciferase reporter assays showed significant inhibition of luciferase expression when the Hsp70 3′UTR was present, indicating that the 3′UTR is responsible for the down-regulation of protein translation. After DSS treatment for 7 days, colonic Hsp70 level did not change in transgenic mouse, but was greatly decrease in wildtype mouse as previously reported. This result suggests that the Hsp70 3′UTR is necessary for translational regulation in inflammation. Furthermore, we found two miRNAs, mmu_let_7f and mmu_miR_155, that were significantly increased in YAMC cells with IFN+ TNF treatment compared to the no-treatment control.These microRNAs are believed to bind to Hsp70 mRNA 3′UTR specificallydueto the high binding energy calculated by the software RNA22 MicroRNA Target Detection. As a result, we conclude that, in intestinal inflammation, epithelial Hsp70 translation is inhibited by cytokine-induced microRNAs through the 3′UTR. These findings of the mechanisms and mediators causing cytokine down-regulation of intestinal epithelial Hsp70 expression will provide important insights into therapeutic strategies to counteract these effects, and, in doing so, reduce the extent and severity of mucosal lesions in IBD.

Twelve‐year clinico‐therapeutic experience in pemphigus: A retrospective study of 54 cases

Pemphigus, a common immunobullous disease of skin and mucous membranes affecting both sexes of all ages, was almost fatal before the advent of corticosteroids. Better strategies to avoid their side-effects and recent introduction of adjuvant therapy has further improved its prognosis. As the treatment remains need-based and patient-specific, different regimens and strategies have evolved, each with its own merits and demerits. This retrospective hospital-based study was carried out to understand the clinico-therapeutic aspects of pemphigus in our clinic. Medical records of all new patients admitted to our hospital with the diagnosis of pemphigus from 1990 to 2002 were analyzed. The diagnosis was mainly clinical and confirmed by positive Tzanck's test and histopathology. All patients were assessed clinically on a severity score of 1+ to 4+. These patients had received treatment with dexamethasone-cyclophosphamide pulse (DCP) therapy, oral mini-pulse (OMP) with betamethasone, or intramuscular triamcinolone acetonide alone or with azathioprine, dapsone or cyclophosphamide. They were followed up for clinical remission and side-effects of therapy. There were a total of 54 new patients comprising 53.7% females and 46.3% males, and 12.9% of these were < 18 years of age. Pemphigus vulgaris was the commonest clinical type seen in 81.48% and mucosal involvement was seen in 63.63% of cases. The severity of mucosal lesions was not proportionate to that of cutaneous lesions. Associated diseases seen were seropositive rheumatoid arthritis, hypertension, diabetes mellitus and hyperthyroidism in one case each. Dexamethasone-cyclophosphamide pulse therapy was given to 75% of the pemphigus vulgaris patients while those having less severe disease were treated with other regimens. In general, clinical remission was seen after 2-16 (mean 6.5) DCP doses. Two patients have been in complete remission for the last 5 and 7 years of completion of DCP therapy, respectively. Addition of other adjuvants to corticosteroids was also helpful. However, azathioprine 50 mg/day was not as effective as cyclophosphamide 50 mg/day. Menstrual irregularities, amenorrhoea, azoospermia, rise in blood pressure and glycosuria were the major side-effects seen during DCP pulse therapy. Drop out rate was unacceptably high with all modes of treatment, although with DCP therapy it appears to be partly owing to early disease control. There was no mortality in this series. Pemphigus vulgaris is the commonest clinical type. Mucosal surfaces other than the oral cavity are uncommonly involved, it may herald the onset of disease and takes longer to heal. Dexamethasone-cyclophosphamide pulse therapy seems to have a definite advantage over treatment with steroids alone, especially in terms of better control of disease activity, near absence of steroid side-effects and significantly reduced hospital stay. However, ways and means to reduce gonadal toxicity of adjuvants need to be explored as DCP therapy is likely to stay as a treatment of choice.

Induction of Colitis in Young Rats by Dextran Sulfate Sodium.

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

This month in Gastroenterology

This month in Gastroenterology

Atropine-induced gastrointestinal cytoprotection dependences to the intact of vagal nerve against indomethacin-induced gastrointestinal mucosal and microvascular damage in rats

The non-steroidal antiinflammatory drugs, such as an indomethacin (IND), cause mucosal ulceration and increase the mucosal vascular permeability in the gastrointestinal (GI) tract. Some exogenous agents, e.g. the atropine, can protect the GI mucosa against these ulcerogenic effects. The gastrointestinal functions and mucosal protection, however, are regulated by the vagal nerve. The aims of this study was to examine the dependence of atropine-induced GI cytoprotection to the vagal innervation against the development of IND-caused ulcers and microvascular damage in the mucosa of stomach and small intestine in rats. Methods: the observations were carried out on CFY-strain rats. The mucosal damage was produced by subcutaneous administration of IND in a 20 mg/kg dose 24 h prior to the killing of animals at the same time as the start of atropine-application, which was given in a small dose (0.1 mg/kg) every 5 h. The subdiaphragmatic bilateral surgical vagotomy was done 24 h before the experiment. The vascular permeability, indicated by the microvascular endothel damage, was measured by the appearance and concentration of intravenously administered Evans blue into the GI mucosa. The number and severity of mucosal lesions and the Evans blue content of mucosa were determined in the stomach and small intestine. Results: (1) The IND caused mucosal ulcers and Evans blue extravasation into the mucosa of the stomach and small intestine. (2) The IND-induced mucosal ulceration and vascular permeability significantly decreased after atropine-administartion in the same parts of GI tract. (3) The extent of cytoprotective effect of atropine against the IND was decreased after bilateral surgical vagotomy. Conclusions: (1) The IND causes microvascular endothel damage in the stomach and small intestinal. (2) The atropine has a cytoprotective effect in the stomach and small intestine against the aggressive effects of IND without decrease of gastric acid secretion. (3) The intact vagal nerve is necessary to the function of cytoprotective mechanisms of atropine against the IND.

Role of heat shock proteins in gastric mucosal protection.

Heat shock proteins (HSP) are crucial for the maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. Gastric surface mucous cells are the first line of defence against insults derived from ingested foods and Helicobacter pylori infection. Primary cultures of gastric surface mucous cells from guinea-pig fundic glands exhibited a typical heat shock response after exposure to elevated temperature or metabolic insults, such as ethanol and hydrogen peroxide, and they were able to acquire resistance to these stressors. Restraint and water immersion stress rapidly activated heat shock factor 1 (HSF1) in rat gastric mucosa within 15 min and induced HSP70 mRNA expression and its protein accumulation. The extent of the induction inversely correlated with the severity of mucosal lesions, suggesting an important role of HSP70 in gastric mucosal defence. This heat shock response appeared to be mediated by the alpha1A-adrenoceptor. The HSP70 family functions as a molecular chaperone and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to its chaperoning activities, HSP70 has been suggested to exert its cytoprotective action by protecting mitochondria and by interfering with the stress-induced apoptotic programme. Recently, we introduced geranylgeranylacetone as a non-toxic HSP70 inducer. This compound weakly stimulated HSP70 induction in cultured gastric mucosal cells and gastric mucosa by directly activating HSF1 and markedly augmented HSP70 induction in response to subsequent exposure to stress. Thus, non-toxic HSP70 inducers may have a potential benefit for the prevention and treatment of stress ulcer.