Search

Seaweed lectins are very promising biotechnological tools that also gain prominence when applied to the pharmacology field. The purpose of the present work was to isolate and characterize lectin from the red algae Amansia multifida and subsequently test it in general inflammation models. The lectin was purified by ion exchange chromatography, characterized with two-dimensional electrophoresis, automated analysis of amino acid sequences and circular dichroism spectroscopy. The pharmacological tests performed were paw edema induced by carrageenan or rapid inflammatory mediators, peritonitis induced by carrageenan and myeloperoxidase leukocyte count assays, glutathione and cytokine concentration. Our results have identified a 30 KDa molecular weight protein that presents a major secondary structure arranged in β-strand elements (~43%). A fragment of 20 amino acid residues was sequenced and presented low identity to the known classes of lectins from marine alga. This lectin was able to modulate inflammatory parameters such as paw edema, leukocyte migration, oxidative stress and proinflammatory cytokines. Thus, the lectin from the seaweed Amansia multifida has evident anti-inflammatory properties because it acts by reducing the formation of edema by modulating the effect of vascular mediators, migration of neutrophils, proinflammatory cytokines and oxidative stress control.

Sulfated polysaccharides derived from seaweeds have important biological activities. The aim of this work was to demonstrate the anti-inflammatory effect of a sulfated polysaccharide extracted from the seaweed Digenea simplex (Wulfen) C. Agardh 1822 on 2,4,6-trinitrobenzene sulfonic acid–induced colitis in rats. After inducing colitis, rats were euthanized, and the colon was excised to determine macroscopic lesion scores and wet weight and to histologically evaluate and quantify glutathione, malondialdehyde, myeloperoxidase, nitrate/nitrite, and cytokines. The polysaccharide, composed of β-d-galactose and 3,6-α-l-anhydrogalactose residues, reduced wet weight as well as macroscopic and microscopic lesion scores. It also reduced myeloperoxidase activity; reduced proinflammatory cytokines, malondialdehyde, and nitrate/nitrite levels; and preserved glutathione consumption in the colon. According to these results, we can infer that the sulfated polysaccharide derived from D. simplex has an anti-inflammatory effect on induced colitis in vivo.

Choledocholithiasis is the most frequent cause of biliary obstruction commonly seen in gastroenterological practice. Objective: evaluate the rate and factors related to success and complications in patients with choledocholithiasis, referred or ERCP in HUWC- UFC. Methodology: Retrospective study of 56 patients submitted to 67 examinations for choledocholithiasis from 01/2017 to 04/2018. The information was taken from the Endoscopy unit medical records database. Success rates (complete withdrawal of calculus), complications (pancreatitis, hemorrhage and perforation), and factors related to these outcomes were analyzed. CEP: 43321014.6.0000.5045. Results: There was a predominance of women (80%), in their early 50 years old. The success rate was 89%. With surgical therapeutic complementation in 9%. 2% of the cases are still under follow-up. The most frequent complication was pancreatitis (7%), being (1) patient with evolution to death (1.8%) without perforations or bleeding. There was an association between the presence of large stones (p = 0.05) and bile duct disproportion (p = 0.01) with ERCP failure. There was no association of the factors evaluated, with the presence of complications. Conclusion: The study shows that there was a high success rate, as described in the literature. The presence of large stones and disproportion, factors related to ERCP failure. A coledocolitíase é a causa mais frequente de obstrução biliar comumente vista na prática gastroenterológica. Objetivo: avaliar taxa e fatores relacionados ao sucesso assim como complicações nos pacientes com coledocolitíase, encaminhados para CPRE no HUWC-UFC. Metodologia: Estudo retrospectivo de 56 pacientes submetidos a 67 CPREs por coledocolitíase de 01/2017 a 04/2018. As informações foram retiradas do banco de dados da unidade de Endoscopia e prontuários. Analisadas as taxas de sucesso (retirada completa dos cálculos), complicações (pancreatite, hemorragia e perfuração) e fatores relacionados a estes desfechos. CEP: 43321014.6.0000.5045. Resultados: Houve predominância de mulheres (80%), com idade média de 51 anos. A taxa sucesso foi 89%. Com complementação terapêutica cirúrgica em 9%. 2% dos casos, estão ainda em seguimento ambulatorial. A complicação mais frequente foi pancreatite (7%), sendo (1) paciente com evolução ao óbito (1,8%). Sem a existência de perfurações ou hemorragias. Houve associação entre a presença de cálculos grandes (p= 0.05) e desproporção da via biliar (p=0.01) com insucesso da CPRE. Não houve nenhuma associação dos fatores avaliados com a presença de complicações. Conclusão: O estudo demonstra que houve alta taxa de sucesso, como descrito na literatura, sendo a presença de cálculos grandes e desproporção fatores relacionados ao insucesso da CPRE.

Background: Inflammatory bowel disease (IBD) is associated with delay in gastric emptying, increase in ghrelin, and decrease in leptin. The aim was to investigate the correlation between gastroduodenal (GD) symptoms, gastric emptying, and serum levels of active ghrelin and leptin in IBD. Twenty-seven IBD patients and 26 healthy volunteers were asked to complete the Porto Alegre Dyspeptic Symptoms Questionnaire. A gastric emptying test for solids was performed using a C13 octanoic acid breath test. During this test, serum samples were collected for measuring active ghrelin and leptin concentrations by radioimmunoassay. Summary: Patients with IBD demonstrated delayed gastric emptying compared with healthy volunteers. In patients with GD symptoms, the delay in gastric emptying was more pronounced, and there were significant correlations of satiety and vomiting with gastric emptying. Basal leptin, but not active ghrelin, increased in patients with GD symptoms compared with patients without these symptoms. There were negative correlations between basal active ghrelin with total Porto Alegre score and epigastric pain in IBD patients with GD symptoms. Key Messages: In IBD, satiety and vomiting were associated with delay in gastric emptying. Conversely, epigastric pain had a negative correlation with active ghrelin. Our results suggest that different pathophysiological mechanisms contribute to GD symptoms in IBD.

Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil&rsquo, s semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm&minus, 1, 1368 cm&minus, 1, and 1029 cm&minus, 1, which relate to the vibration of O&ndash, H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 &times, 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.

Seaweeds are sources of biomolecules with biological activities and pharmacological potential - for example, lectins, a group of proteins that can bind reversibly to carbohydrates or compounds containing them. The aim of this study was to elucidate the structural properties of a lectin extracted from the red seaweed Bryothamnion triquetrum (BtL) and to investigate its anti-inflammatory activity in mice. The lectin was purified by precipitation with ammonium sulfate and ion-exchange chromatography. Its secondary structure and tryptophan (Trp) microenvironment were analyzed by circular dichroism spectroscopy and steady-state fluorescence spectroscopy, respectively. The anti-inflammatory effect was evaluated by means of paw edema induced by carrageenan or dextran, myeloperoxidase activity in paw tissue, and by measurement of leukocyte and neutrophil migration and cytokine quantification in a peritonitis model. The secondary structure of BtL is mostly composed of β-strands and unordered conformation, and it is quite resistant to extremes of pH and temperature, preserving the exposure of Trp residues under these conditions. In an assessment of biological activities, groups of mice were subjected to pretreatment with BtL before the inflammatory stimulus. BtL had anti-inflammatory effects in the models tested, and hence may be considered a molecule with potential to be used in the pharmaceutical industry.

Intestinal mucositis (IM) is a common side effect of irinotecan-based chemotherapy. The involvement of inflammatory mediators, such as TNF-α, IL1-β, IL-18 and IL-33, has been demonstrated. However, the role of adaptive immune system cells, whose activation is partially regulated by these cytokines, is yet unknown. Thus, we investigated the role of regulatory T cells (Tregs) in irinotecan-induced IM. C57BL/6 mice were injected with saline or irinotecan (75 mg kg− 1, i.p.), once a day for 4 days, and euthanized at day 1, 3, 5 or 7 following the first dose of irinotecan. For Treg depletion, the mice were pretreated with a low single dose of cyclophosphamide (100 mg kg− 1, i.p). Intestinal lamina propria lymphocytes were harvested and purified by Percoll gradient. Treg and Th17 cells were identified by flow cytometry. Blood leukocyte count was obtained and ileum samples were collected for histopathological analysis and myeloperoxidase assay. IM caused an accumulation of Tregs and Th17 cells over time. Treg depletion exacerbated intestinal damage, diarrhea, neutrophil infiltration and animal mortality, despite a reduction in Th17 cell number. The frequency of other Th cells increased and was positively correlated with neutrophil infiltration. Tregs showed a negative correlation with neutrophils and the frequency of non-regulatory Th cells. In conclusion, Tregs are important in the control of intestinal damage induced by irinotecan, and their depletion showed a deleterious effect on IM. Activation of these cells appears to be a compensatory mechanism for intestinal inflammation.

Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5 ml/kg i.p.), IRI (50 mg/kg i.p.), SIL (150 mg/kg p.o.) or IRI (50 mg/kg i.p.) + (SIL 1.5, 15 or 150 mg/kg p.o.) thrice/week/7 weeks. On the seventh week, blood samples were collected for transaminases assay and livers were collected for histopathology, measurement of the total lipids, malondyadehyde (MDA), non-protein sulfhydryl groups (NPSH), cytokines (IL-1β, IL 6 and IL-10), 3-nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression, quantification of NF-kB, α-smooth muscle actin (α-SMA), and Escherichia coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases, neutrophil infiltration, lipid accumulation, MDA, IL-1β and IL-6 levels, N-Tyr and TLR4 immunostaining, NF-kB, α-SMA expression and RRS versus the SAL group (p < 0.05). Additionally, SIL (1.5 mg/kg) improved these parameters (p < 0.05), except neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL (15 mg/kg) only improved the inflammatory parameters, the expression of α-SMA and RRS versus the IRI group (p < 0.05). The higher dose of SIL (150 mg/kg) was even more deleterious than the intermediate dose. Therefore, silymarin showed a dual effect on liver damage induced by IRI. Hepatoprotection seems to involve the inhibition of oxidative stress and protein nitrosylation, preventing activation of hepatic fibrosis mechanisms.

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD.NEW & NOTEWORTHY In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder.

Objective This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats. Methods Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30 mg/kg, p.o. or i.p. , groups 3–5, respectively) twice daily, for 2 days. After 1 h, NAP (80 mg/kg, p.o. ) was given. The control group received only vehicle (group 1) or vehicle + naproxen (group 2). Rats were euthanized on 2nd day, 4 h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated. Results EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10 mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4 ± 0.3 U/mg of gastric tissue) and inhibited changes in MDA (70.4 ± 8.3 mg/g of gastric tissue) and GSH (246.2 ± 26.4 mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group. Conclusion Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF.

Background and aim Chemotherapy drugs that act via Toll-like receptors (TLRs) can exacerbate mucosal injury through the production of cytokines. Intestinal mucositis can activate TLR2 and TLR4, resulting in the activation of NF-κB. Intestinal mucositis characterized by intense inflammation is the main side effect associated with 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii CNCM I-745 (S.b) is a probiotic yeast used in the treatment of gastrointestinal disorders. The main objective of the study was to evaluate the effect of S.b treatment on the Toll-like/MyD88/NF-κB/MAPK pathway activated during intestinal mucositis and in Caco-2 cells treated with 5-FU. Methods The mice were divided into three groups: saline (control), saline + 5-FU, and 5-FU + S.b (1.6 × 1010 colony forming units/kg). After 3 days of S.b administration by gavage, the mice were euthanized and the jejunum and ileum were removed. In vitro, Caco2 cells were treated with 5-FU (1 mM) alone or in the presence of lipopolysaccharide (1 ng/ml). When indicated, cells were exposed to S.b. The jejunum/ileum samples and Caco2 cells were examined for the expression or concentration of the inflammatory components. Results Treatment with S.b modulated the expressions of TLR2, TLR4, MyD88, NF-κB, ERK1/2, phospho-p38, phospho-JNK, TNF-α, IL-1β, and CXCL-1 in the jejunum/ileum and Caco2 cells following treatment with 5-FU. Conclusion Toll-like/MyD88/NF-κB/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.

This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFU•g body wt−1•day−1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm2) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 μmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.

Simple Summary The detection of early-stage colorectal cancer increases the chance to prevent tumor progression and death by the disease. Colonoscopy is one sensitive screening test to detect malignant or potentially malignant lesions in the intestines. However, it has some disadvantages, including sedation requirements, increased risk of colon perforation, and bleeding. Circulating microRNAs (miRNAs) in plasma or serum from cancer patients have been investigated and described as potential diagnostic or prognostic markers. We conducted an miRNAs screening test in plasma samples from colorectal cancer patients and subjects without cancer, aiming to identify markers for the early detection of the disease. We identified and validated four miRNAs capable of distinguishing cancer from non-cancer cases. Our non-invasive diagnostic biomarkers presented high performance and are easily applicable to clinical practice. Abstract Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

Background This study aimed to investigate and characterize the anti-inflammatory and anti-hypernociceptive effects of the total polysaccharides of X. americana (TPL-Xa) bark in a mouse model of acute pancreatitis-induced by caerulein and the potential involvement of cannabinoid receptors. Methods TPL-Xa was characterized by1H and 13C NMR spectroscopy. Animals received TPL-Xa (10 mg/kg, i.v.) 30 min before and after caerulein (50 μg/kg, 10×, i.p.) administration. To evaluate the involvement of cannabinoid receptors, AM281 (3 mg/kg, s.c.) and AM630 (1 mg/kg, s.c.) were administered 30 min before TPL-Xa. Plasma levels of amylase and lipase, pancreatic myeloperoxidase (MPO), histology, visceral hypernociception and motor coordination were evaluated 11 and 24 h after acute pancreatitis (AP) induction. Results TPL-Xa, containing a heteropolysaccharide composed of glucose, galactose, arabinose, rhamnose, fucose and galacturonic acid, reduced amylase and lipase levels, MPO activity, acinar cell necrosis, edema and neutrophil infiltration. TPL-Xa increased the threshold of visceral hypernociception, an effect reversed by AM630, an antagonist of cannabinoid receptor type 2 (CB2). In addition, TPL-Xa did not alter the animals’ motor coordination. Conclusions TPL-Xa contains heteropolysaccharides that inhibit inflammation and hypernociception in the experimental model of caerulein-induced AP, by a mechanism involving type CB2 receptors.

Introdução: pacientes com doença do refluxo gastroesofágico (DRGE) têm de 10 a 15% de chance de desenvolver esôfago de Barrett. Este pode evoluir para displasia e adenocarcinoma esofágico. Objetivo: avaliar fatores relacionados à detecção de displasia em pacientes com esôfago de Barrett longo. Metodologia: estudo retrospectivo com análise de informações de 18 pacientes com diagnóstico de esôfago de Barrett longo, colhidas de bancos de dados dos serviços de Endoscopia e Patologia e prontuários do Hospital Universitário Walter Cantídio (HUWC-UFC), no período de 2010 a 2015. Os pacientes foram divididos em dois grupos para comparação, grupo sem displasia (N=11) e grupo com displasia/adenocarcinoma (N=7). Resultados: do total de 18 pacientes com esôfago de Barrett longo no HUWC, 72% eram do sexo masculino, 47% tinham mais de 50 anos, 64% apresentavam sintomas típicos de DRGE, 23% eram tabagistas, 77% tinha hérnia hiatal, 50% realizaram fundoplicatura. Não houve diferenças estatísticas destas características entre o grupo com e sem displasia. Entretanto, o grupo com displasia teve uma média de 5 endoscopias/paciente, enquanto o grupo sem displasia teve apenas 2 endoscopias/paciente(p

CHAVES, Hellíada Vasconcelos Objective and design To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. Materials and Methods Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg−1), DMDC (0.025, 0.25, or 2.5 µmol kg−1), biliverdin (1, 3, or 10 mg kg−1), or ZnPP-IX (1, 3 or 9 mg kg−1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg−1; s.c.) or glibenclamide (10 mg kg−1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg−1; s.c), respectively. Results Hemin (1 mg kg−1), DMDC (2.5 µmol kg−1), and BVD (10 mg kg−1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg−1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1β mRNA expression and immunolabelling increased. Conclusions HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6-50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (n = 8/group) were injected with saline, IFO (400 mg/kg, i.p.), fucoidan (a P- and L-selectins inhibitor, 100 mg/kg, i.v.) or IFO + fucoidan (1-100 mg/kg) alone or combined with mesna (80 mg/kg i.p.). Another group of mice received anti-Ly6G antibody (500 μg/mouse, once daily for 2 days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony-stimulating factor (G-CSF, 400 μg/kg), IFO (200 mg/kg), G-CSF (25-400 μg/kg, for 5 days) + IFO (200 mg/kg, i.p.) or fucoidan + G-CSF + IFO. Bladder injury was evaluated 12 h after IFO injection. IFO 400 mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL-1β and IL-6 tissue levels, and COX-2 immunostaining and expression versus the saline group (P < 0.05). Conversely, fucoidan (100 mg/kg) significantly attenuated these parameters compared to IFO-injected mice (P < 0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFO + mesna group (P < 0.05). Accordingly, neutrophil depletion with anti-Ly6G reduced inflammatory parameters and bladder injury compared to IFO (P < 0.05). In contrast, G-CSF enhanced IFO (200 mg/kg)-induced HC, which was significantly attenuated by treatment with fucoidan (P < 0.05). Therefore, neutrophils contribute to the pathogenesis of HC.

Objectives The aim of the study was to investigate the anti-inflammatory, antioxidant and antinociceptive actions of PFPe, a polysaccharide fraction isolated from the dried fruit of the Passiflora edulis. Methods Animals were pretreated with PFPe (0.3, 1 or 3 mg/kg, i.p.) 1 h before induction of paw oedema by carrageenan, histamine, serotonin, compound 48/80 or prostaglandin E2 (PGE2). Neutrophil migration and vascular permeability were measured after carrageenan injection into the peritoneum, and the action of the PFPe on the tumour necrosis factor-alpha, interleukin-1 beta (IL-1β), myeloperoxidase (MPO), glutathione (GSH) and malondialdehyde (MDA) levels was also evaluated. To assay nociception, we examined acetic acid-induced writhing, formalin-induced paw licking and response latency in the hot plate test. Key findings Pretreatment with PFPe significantly inhibited carrageenan-induced paw oedema. PFPe also reduced paw oedema induced by compound 48/80, histamine, serotonin, and PGE2 and compound 48/80-induced vascular permeability. In addition, PFPe significantly reduced the MPO activity, MDA and GSH concentrations, and IL-1β level. In the nociception tests, PFPe reduced acetic acid-induced writhing and formalin-induced paw licking and did not increase the response latency time. Conclusions Our results suggest that PFPe administration reduces the inflammatory response by modulation of the liberation or synthesis of histamine and serotonin, by reduction of neutrophil migration, IL-1β levels, and oxidative stress and nociception.

Background and Purpose Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL-18 in the pathogenesis of irinotecan-induced intestinal mucositis. Experimental Approach Wild type (WT), IL-18 or caspase-1 knockout mice were treated with either saline or irinotecan (60 mg·kg−1 per 4 days, i.p.) or the IL-18 binding protein (IL-18bp, 10 mg·kg−1) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL-18 expression. Key Results Irinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL-18 expression in WT mice compared with saline treatment. The IL-18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase-1 knockout and IL-18 knockout mice, and in IL-18bp-treated WT mice. Furthermore, the Survival of irinotecan-treated mice was increased and iNOS immunoexpression and IL-18 production prevented in IL-18 knockout mice. Conclusions and Implications Targeting IL-18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens.

The crural diaphragm (CD) is an essential component of the esophagogastric junction (EGJ), and inspiratory exercises may modify its function. This study's goal is to verify if inspiratory muscle training (IMT) improves EGJ motility and gastroesophageal reflux (GER). Twelve GER disease [GERD; 7 males, 20–47 yr, 9 esophagitis, and 3 nonerosive reflex disease (NERD)] and 7 healthy volunteers (3 males, 20–41 yr) performed esophageal pH monitoring, manometry, and heart rate variability (HRV) studies. A 6-cm sleeve catheter measured average EGJ pressure during resting, peak inspiratory EGJ pressures during sinus arrhythmia maneuver (SAM) and inhalations under 17-, 35-, and 70-cmH2O loads (TH maneuvers), and along 1 h after a meal. GERD patients entered a 5-days-a-week IMT program. One author scored heartburn and regurgitation before and after IMT. IMT increased average EGJ pressure (19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg; P < 0.001) and inspiratory EGJ pressure during SAM (89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg; P = 0.001) and during TH maneuvers. The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers. The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT. Proximal progression of GER decreased after IMT but not the distal acid exposure. Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure. IMT decreased heartburn and regurgitation scores. In conclusion, IMT improved EGJ pressure, reduced GER proximal progression, and reduced GERD symptoms. Some GERD patients have a CD failure, and IMT may prove beneficial as a GERD add-on treatment.

Seaweeds are the most abundant source of polysaccharides such as alginates and agar, as well as carrageenans. This study aimed to investigate the gastroprotective activity and the mechanism underlying this activity of a sulfated-polysaccharide fraction extracted from the algae Hypnea musciformis (Wulfen) J.V. Lamour. (Gigartinales– Rhodophyta). Mice were treated with sulfated-polysaccharide fraction (3, 10, 30, and 90 mg/kg, p.o.) and, after 30 min, they were administered 50% ethanol (0.5 mL/25 g, p.o.). After 1 h, gastric damage was measured using a planimeter. In addition, samples of the stomach tissue were obtained for histopathological examination and for assays to determine the glutathione and malondialdehyde levels. Other groups of mice were pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.), aminoguanidine (100 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.). After 30 min to the aminoguanidine group and 1 h to the other groups, sulfated-polysaccharide fraction (30 mg/kg, p.o.) was administered and gastric damage was induced as described above. Sulfated-polysaccharide fraction prevented ethanol-induced gastric injury in a dosedependent manner. However, treatment with L-NAME or glibenclamide reversed this gastroprotective effect. Administration of aminoguanidine did not infl uence the effect of sulfated-polysaccharide fraction. Our results suggest that sulfated-polysaccharide fraction exerts a protective effect against ethanol-induced gastric damage via activation of the NO/KATP pathway. Keywords: sulfated polysaccharide, nitric oxide, gastric damage, ethanol

Background/purpose The mechanism of fetal gastric dilation in gastroschisis is controversial. This study was designed to characterize changes in the contractile profile of strips of stomach from rats following experimental gastroschisis. Methods Pregnant Wistar rats were operated on day 18.5. Fetuses were divided into three groups: gastroschisis (G), sham (S), and control (C). On day 21.5, gastric fundus and antrum strips were obtained and suspended to a force transducer connected to a digital data acquisition system. They were submitted to increasing concentrations of carbachol (CCh) and weighed at the end of each procedure. Frequency and amplitude of each contraction were evaluated. Results Under basal conditions, spontaneous oscillatory contractions of antrum and fundus strips of G, S, and C were similar (P>0.05; ANOVA). However, cumulative concentrations of CCh (0.01–100μM) produced different effects in all groups and were characterized by a significant increase in amplitude and frequency of spontaneous contractions in antral smooth muscle and a sustained increase in tonus in fundic strips. Upon analysis, no significant difference in frequency or amplitude was noted in antral tissues comparing C to G and to S (P>0.05). No significant contractility difference was noted in fundic smooth muscle (comparing all groups, P >0.05), with the CCh-induced curve following a typical sigmoidal format, dependent on increasing concentrations (P Conclusions Gastric contractile responses to CCh are preserved in experimental gastroschisis. These results do not support the theory that gastric dilation occurs secondary to intestinal inflammation alone.

Background 5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis. Methods IL-4 +/+ or IL-4 −/− mice (25–30 g) were intraperitoneally injected with 5-FU (450 mg/Kg) or saline (C). After 3 days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration. Results 5-FU induced significant damage in the intestinal epithelium of IL-4 +/+ mice (reduction in the villus/crypt ratio: control = 3.31 ± 0.21 μm, 5-FU = 0.99 ± 0.10 μm). However, the same treatment did not induce significant damage in IL-4 −/− mice (5-FU = 2.87 ± 0.19 μm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1β and CXCL-8) in the duodenum. These results were not observed in IL-4 −/− mice treated with 5-FU. Conclusion Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.

Our objective was to evaluate the role of soluble guanylate cyclase (sGC) activation in the gastroprotective effect of the HO-1/CO pathway against alendronate-induced gastric damage in rats. Rats were pretreated, once daily for 4 days, with saline, hemin (HO-1 inducer), or dimanganese decacarbonyl (DMDC, CO donor). Another group received zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist) 1h before hemin treatment or sGC inhibitor (ODQ) 30min before hemin and DMDC treatment. After 30min, gastric damage was induced by alendronate (30mg/kg) by gavage. On the last day of treatment, 4h after alendronate administration, the animals were killed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), myeloperoxidase (MPO), or bilirubin. Another group was used to measure gastric mucus. HO-1 expression was determined after saline or alendronate administration by immunohistochemistry. Alendronate induced gastric damage, produced neutrophil accumulation, increased MDA levels and MPO activity, and reduced GSH and mucus in the gastric tissue. Alendronate also increased HO-1 immunoreactivity and the level of bilirubin in gastric mucosa. Pretreatment with hemin or DMDC reduced neutrophil infiltration and TNF-α, IL-1β, and MDA formation, and increased the levels of GSH and mucus in the gastric tissue. ODQ completely abolished the gastroprotective effect of hemin and DMDC and increased alendronate gastric damage. Our results suggest that the HO-1/CO pathway plays a protective role against alendronate-induced gastric damage through mechanisms that can be dependent on sGC activation.

BACKGROUND - Gastric polyps are elevated mucosal lesions. Most of them are less than 1 cm and when larger than 2 cm, has a high malignancy probability. The histopathological types are mainly fundic gland polyps, hyperplastic polyps and adenomatous polyps. OBJECTIVE - To evaluate the agreement between three different pathologists in the histopathological diagnosis of 128 biopsied gastric polyps in Digestive Endoscopy Unit from Walter Cantídeo University Hospital, between May 2010 to May 2012. METHODS - To describe the intensity of agreement between observers, we use kappa index that is based on the number of concordant measures between them. RESULTS - There was substantial agreement in the diagnosis of adenoma (kappa=0.799, CI: 0.899-0.698) and fundic glands (kappa=0.655, CI: 0.755-0.555). Regarding to hyperplastic polyps (kappa=0.415, CI: 0.515-0.315) and inflammatory (kappa=0.401, CI: 0.501-0.301), we obtained a moderate agreement. Regarding the presence of Helicobacter pylori in biopsy of the polyp, there was a low agreement (kappa=0.219, CI: 0.319-0.119). CONCLUSION - It is clear that the agreement between pathologists depends on the histological type of the biopsied polyp and this agreement is more substantial in adenoma, or fundic gland polyps. RESUMO CONTEXTO - Os pólipos gástricos são lesões elevadas da mucosa. A maioria são menores que 1 cm (60%-82%) e quando maiores do que 2 cm, tem alta probabilidade de malignidade. Os tipos histopatológicos são principalmente pólipos de glândulas fúndicas, pólipos hiperplásicos e pólipos adenomatosos. OBJETIVO - Avaliar a concordância entre três diferentes patologistas no diagnóstico histopatológico de 128 pólipos gástricos biopsiados na Unidade de Endoscopia Digestiva do Hospital Universitário Walter Cantídeo no período de maio de 2010 a maio de 2012. MÉTODOS - Para descrevermos a intensidade de concordância entre os avaliadores, utilizamos o índice kappa que é baseado no número de medidas concordantes entre eles. RESULTADOS - Houve uma substancial concordância no diagnóstico de adenoma (kappa=0,799, IC: 0,899-0,698) e glândulas fúndicas (kappa=0,655, IC: 0,755-0,555). Em relação aos pólipos hiperplásicos (kappa=0,415, IC: 0,515-0,315) e inflamatórios (kappa=0,401, IC: 0,501-0,301), obtivemos uma concordância moderada. Em relação à presença do Helicobacter pylori na biópsia do pólipo, houve uma baixa concordância (kappa=0,219, IC: 0,319-0,119). CONCLUSÃO - Em vista do que foi observado, torna-se claro que a concordância entre observadores depende do tipo histológico do pólipo biopsiado, sendo essa mais alcançada no diagnóstico de adenoma e pólipos de glândulas fúndicas.

The objective was to evaluate the effects of nitric oxide (NO) and hydrogen sulfide (H2S) donors and possible interactions between these two systems in modulating gastric function. Mice received saline, sodium nitroprusside (SNP), or sodium hydrosulfite (NaHS), and after 1 h, the animals were killed for immunofluorescence analysis of CSE or eNOS expressions, respectively. Other groups received saline, SNP, NaHS, Lawesson’s reagent (H2S donor), PAG + SNP, l-NAME, l-NAME + NaHS, or l-NAME + Lawesson’s reagent. Then, the gastric secretions (mucous and acid), gastric blood flow, gastric defense against ethanol, and gastric motility (gastric emptying and gastric contractility) were evaluated. SNP and NaHS increased the expression of CSE or eNOS, respectively. SNP or Lawesson’s reagent did not alter gastric acid secretion but increased mucus production, and these effects reverted with PAG and l-NAME treatment, respectively. SNP or NaHS increased gastric blood flow and protected the gastric mucosa against ethanol injury, and these effects reverted with PAG and l-NAME treatments, respectively. SNP delayed gastric emptying when compared with saline, and PAG partially reversed this effect. NaHS accelerate gastric emptying, and l-NAME partially reversed this effect. SNP and NaHS alone induced gastric fundus and pylorus relaxation. However, pretreatment with PAG or l-NAME reversed these relaxant effects only in the pylorus but not in the gastric fundus. NO and H2S interact in gastric physiological functions, and this “cross-talk” is important in the control of mucus secretion, gastric blood flow, gastric mucosal defense, and gastric motility, but not in the control of basal gastric acid secretion.

Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis. A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion. Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis. IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.

Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg(-1), p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g(-1), p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg(-1), i.p.), dl-propargylglycine (PAG, 50 mg·kg(-1), p.o.) or glibenclamide (5 mg·kg(-1), i.p.). After 1 h, PLS (30 mg·kg(-1), p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25 g(-1), p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/K(ATP) pathway.

Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 microg) or Dextran (200 microg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (microg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7%). IPC inhibited VE (38.8%) and VP (54%) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3%; NM: 64%). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

This study aims to show pelvic floor dysfunctions in women with obstructed defecation syndrome (ODS), comparing nulliparous to those with vaginal delivery or cesarean section using the echodefecography (ECD). Three hundred seventy female patients with ODS were reviewed retrospectively and were divided in Group I—105 nulliparous, Group II—165 had at least one vaginal delivery, and Group III—comprised of 100 patients delivered only by cesarean section. All patients had been submitted to ECD to identify pelvic floor dysfunctions. No statistical significance was found between the groups with regard to anorectocele grade. Intussusception was identified in 40% from G I, 55.0% from G II, and 30.0% from G III, with statistical significance between Groups I and II. Intussusception was associated with significant anorectocele in 24.8%, 36.3%, and 18% patients from G I, II, and III, respectively. Anismus was identified in 39.0% from G I, 28.5% from G II, and 60% from G III, with statistical significance between Groups I and III. Anismus was associated with significant anorectocele in 22.8%, 15.7%, and 24% patients from G I, II, and III, respectively. Sigmoidocele/enterocele was identified in 7.6% from G I, 10.9% G II, and was associated with significant rectocele in 3.8% and 7.3% patients from G I and II, respectively. The distribution of pelvic floor dysfunctions showed no specific pattern across the groups, suggesting the absence of a correlation between these dysfunctions and vaginal delivery.

Background and purpose: Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (KATP) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol-induced gastric damage. Experimental approach: Rats were treated with L-NAME (1 or 3 mg kg−1, i.p.) or with L-arginine (200 mg kg−1, i.p.) +L-NAME (3 mg kg−1, i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg−1, i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg−1, i.p.) or with glibenclamide (1 mg kg−1, i.p.) + diazoxide (3 mg kg−1, i.p.). After thirty minutes, the rats received sildenafil (1 mg kg−1, by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg−1) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. Key results: Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. Conclusions: Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/KATP pathway. British Journal of Pharmacology (2008) 153, 721–727; doi:10.1038/sj.bjp.0707605; published online 10 December 2007

Objective: Inflammatory bowel disease (IBD) is associated with elevated levels of anxiety and depression and a reduction in health-related quality of life (HRQoL). Nonadherence to treatment is also frequent in IBD and compromises outcomes. Religious coping plays a role in the adaptation to several chronic diseases. However, the influence of religious coping on IBD-related psychological distress, HRQoL, and treatment adherence remains unknown. Method: This cross-sectional study recruited 147 consecutive patients with either Crohn’s disease or ulcerative colitis. Sociodemographic data, disease-related variables, psychological distress (Hospital Anxiety and Depression Scale), religious coping (Brief RCOPE Scale), HRQoL (WHOQOL-Bref), and adherence (8-item Morisky Medication Adherence Scale) were assessed. Hierarchical multiple regression models were used to evaluate the effects of religious coping on IBD-related psychological distress, treatment adherence, and HRQoL. Results: Positive RCOPE was negatively associated with anxiety (b = 0.256; p = 0.007) as well as with overall, physical, and mental health HRQoL. Religious struggle was significantly associated with depression (b = 0.307; p < 0.001) and self-reported adherence (b = 0.258; p = 0.009). Finally, anxiety symptoms fully mediated the effect of positive religious coping on overall HRQoL. Conclusion: Religious coping is significantly associated with psychological distress, HRQoL, and adherence in IBD.

This research investigated the effect of glutamine (Gln) depletion on leucocyte-dependent inflammatory events. Rats were treated intraperitoneally, 16 hr prior to the peak of every parameter evaluated, with either 0.9% NaCl, methionine-sulphoximine (MSO, an inhibitor of endogenous Gln synthesis, 25 mg/kg) or with MSO + Gln (MSO as above plus Gln 3 g/kg in three doses). MSO-induced Gln depletion increased paw oedema induced both by carrageenan (Cg) and by Clostridium difficile toxin A (TxA) (66.2% and 45.5%, respectively; P < 0.05). In dextran-injected animals, oedema and myeloperoxidase (MPO) activity were not modified by Gln depletion. In Cg-treated paws, Gln depletion increased MPO activity by 44% (P < 0.05), interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) concentrations by 47% and 52%, respectively (P < 0.05), and immunostaining for TNF-alpha in paw tissue. In TxA-injected paws, Gln depletion increased MPO activity (46%; P < 0.05). Gln depletion increased Cg- and TxA-induced neutrophil migration to subcutaneous air pouches by 56% and 77% (P < 0.05), respectively, but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). Gln infusions reversed all the effects of MSO. Leucocyte counts did not differ between groups. Gln depletion potentiates acute inflammation, possibly by increasing neutrophil migration through resident cell activation and production of IL-1beta and TNF-alpha. Gln supplementation reverses these effects and may be useful during inflammatory catabolic stress.

Nitric oxide (NO) is an important mediator of gastric mucosal defense. Sildenafil (SILD), a cyclic GMP-specific phosphodiesterase inhibitor, promotes an increase in cGMP concentrations in the gastrointestinal tract. cGMP mediates many of the biological actions of NO. We tested the hypothesis that SILD could increase mucosal defense against indomethacin-induced gastropathy in rats. SILD (1, 4 or 10 mg kg−1, p.o.) pretreatment significantly reduced (P

Racional - A doença de Crohn e a retocolite ulcerativa idiopática são consideradas pouco freqüentes nos países em desenvolvimento, sendo escassos os estudos sobre a sua ocorrência no Brasil. Objetivos - Estudar a freqüência de admissão de casos da doença de Crohn e da retocolite ulcerativa inespecífica em um hospital universitário ao longo de 20 anos (1980-99) e descrever características demográficas e clínicas desses casos. Métodos - Calculou-se a freqüência de admissão de casos da doença de Crohn e da retocolite ulcerativa inespecífica de janeiro de 1980 a dezembro de 1999 e analisaram-se todos os casos destas doenças admitidos nos últimos 10 anos desse período. Resultados - No período estudado, registraram-se 257 casos novos, sendo 126 da doença de Crohn e 131 da retocolite ulcerativa inespecífica. A freqüência de admissão de casos de ambas as doenças aumentou de 40 para 61 casos/10.000 atendimentos, do primeiro para o segundo qüinqüênio, com menor crescimento subseqüente, sendo que a doença de Crohn tornou-se, gradualmente, mais freqüente que a retocolite ulcerativa inespecífica. Em ambas as doenças, houve predomínio de casos do gênero feminino, na faixa etária entre 20 e 50 anos, da cor branca, do estado civil casado e de não-tabagistas. Ambas as doenças apresentaram-se com os sintomas digestivos próprios e não houve diferenças entre elas quanto às freqüências de manifestações sistêmicas e extra-intestinais (29,5% vs 23,3%), incluindo as tromboembólicas (5,9% vs 5,5%). Na doença de Crohn, 59,2% dos casos apresentaram complicações (obstrução e/ou perfuração), enquanto que 53,7% dos casos de retocolite ulcerativa inespecífica foram de formas mais graves. Nos casos de doença de Crohn com obstrução, o tabagismo foi significativamente mais freqüente que nas formas não-complicadas. Na retocolite ulcerativa inespecífica, as manifestações sistêmicas e as extra-intestinais, bem como o acometimento de todo o cólon, foram significativamente mais freqüentes nas formas mais graves. Conclusões - Houve aumento da freqüência das doenças inflamatórias intestinais, com a doença de Crohn tornando-se mais comum que a retocolite ulcerativa inespecífica. Tanto uma como outra das afecções, apresentaram-se com as características habituais, destacando-se o predomínio das formas mais graves.