VACCINE ADHERENCE AND ADVERSE EVENTS OF THE SARS-COV VACCINE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

OBJECTIVE: to assess adherence to and the adverse effects of the SARS-COV vaccine in patients with Inflammatory Bowel Disease (IBD). PATIENTS AND METHODS: This is an observational, analytical, cross-sectional study. Sociodemographic and clinical data, SARS-COV vaccine Data, medications for IBD with use during the vaccination period, and adverse events during the vaccination period were collected. Carried out Logistic regressions with robust variance estimation to estimate the Odds Ratio with the respective 95% Confidence Intervals (95%CI) to assess the factors associated with non-serious adverse effects following vaccine doses as outcome variables. RESULTS: 194 patients participated, with vaccine compliance of 78.3% for three doses of any vaccine (n=152). Local symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. The first dose of the SARS-COV vaccine with AstraZeneca had a higher percentage of patients with vaccine symptoms. AstraZeneca vaccine increased the chance of non-serious adverse effects in IBD patients by 2.65 times (95% CI: 1.38-5.08; p=0.003), regardless of age, gender, physical activity, excess weight, use of disease-modifying drugs, immunobiological and corticosteroids. CoronaVac vaccine was associated with asymptomatic patients at the first dose and reduced the chance of adverse effects by 0.28 times (OR: 0.284; 95%CI: 0.13-0.62; p=0.002). CONCLUSION: Local symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. Using CoronaVac in the first dose reduced the chances of adverse effects, while AstraZeneca increased the risk of adverse effects.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

A polyphenol-rich açaí seed extract protects against 5-fluorouracil-induced intestinal mucositis in mice through the TLR-4/MyD88/PI3K/mTOR/NF-κBp65 signaling pathway.

Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1ß; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway.

A MEDICAL AND NEUROPSYCHIATRIC MANAGEMENT SURVEY IN A BRAZILIAN COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD).

BACKGROUND: Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions. BACKGROUND: • What is already known? BACKGROUND: • The prevalence and spectrum of neuropsychiatric co-morbidities varies among different epidemiologic studies. BACKGROUND: • What is new here? BACKGROUND: • Patients self report a high percentage of neuropsychiatric diseases but tend to better recognize central rather than peripheral nervous system disorders. BACKGROUND: • How can this study help patient care? BACKGROUND: • This study may guide practioners to educate IBD patients about their neuropsychiatric co-morbidities.

Uma pesquisa de manejo médico e neuropsiquiátrico em uma coorte brasileira de pacientes com doença inflamatória intestinal (DII) / A medical and neuropsychiatric management survey in a brazilian cohort of patients with inflammatory bowel disease (ibd)

ABSTRACT Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions.

RESUMO A doença inflamatória intestinal (DII) pode ser acompanhada por vários distúrbios neurológicos. Desde 2004, iniciamos uma coorte brasileira para avaliar complicações neuropsiquiátricas em pacientes com DII. Mudanças na estratégia terapêutica e diferenças na prevalência e relevância dos transtornos neuropsiquiátricos têm sido relatadas na literatura. Realizamos uma breve pesquisa relatada pelos pacientes sobre o manejo médico da DII (com foco especial no manejo neuropsiquiátrico) e suas complicações. Durante o período de 01/09/2021 a 31/08/2022, 279 pacientes com DII responderam à pesquisa (128 pacientes com retocolite ulcerativa e 151 com doença de Crohn). Esta é a primeira pesquisa de gestão médica que visa verificar o nível de percepção dos pacientes com DII acerca de suas condições neuropsiquiátricas. Encontramos uma alta prevalência de comorbidades neurológicas (59%), psiquiátricas (32%) e neuropsiquiátricas (69%). Há uma discrepância marcante entre os achados de distúrbios neurológicos relatados em nossos estudos durante os primeiros 10 anos da coorte em comparação com a percepção/conhecimento atual entre os pacientes da presente pesquisa de manejo. Os pacientes tendem a ter uma melhor compreensão das condições que afetam o sistema nervoso central do que as que afetam o sistema nervoso periférico.

Crucial role of carbon monoxide as a regulator of diarrhea caused by cholera toxin: Evidence of direct interaction with toxin.

The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl- efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.

Laryngeal and Esophageal Mucosal Protection Using the Angico Gum Biopolymer in a Mouse Model of Reflux.

OBJECTIVE: This study aimed to evaluate the in vivo protective effect of the angico gum biopolymer in reducing the inflammatory response and preserving the integrity of the laryngeal and esophageal mucosa. STUDY DESIGN: Animal study. METHODS: A murine surgical model of gastroesophageal reflux disease was accomplished and subsequently treated with angico gum or omeprazole. On days 3 and 7 post surgery, samples of the larynx and esophagus, respectively, were collected to measure the level of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and mucosal permeability to fluorescein). RESULTS: Angico gum and omeprazole decreased laryngeal inflammation (wet weight and myeloperoxidase activity) and dramatically improved the integrity of the laryngeal mucosa. It also reduced inflammation (decreased wet weight and myeloperoxidase activity) of the esophagus and preserved the barrier function (inferred by assessing the integrity of the mucosa). CONCLUSION: This study demonstrates the protective effect of angico gum in an experimental gastroesophageal reflux disease model. Angico gum attenuates inflammation and impairment of the mucosal barrier function not only in the larynx but also in the esophagus. LEVEL OF EVIDENCE: NA Laryngoscope, 133:162-168, 2023.

BILIARY FISTULAS ASSOCIATED WITH LIVER TRANSPLANTATION VERSUS OTHER ETIOLOGIES: WHAT IS THE SUCCESS RATE OF THE ENDOSCOPIC TREATMENT?

BACKGROUND: Biliary fistulas typically occur as surgical complications after laparoscopic cholecystectomy, liver transplantation, or partial liver resection. AIMS: This study aimed to evaluate the efficacy of the endoscopic treatment of biliary fistulae secondary to liver transplantation compared to that of other etiologies. METHODS: A retrospective study of 25 patients undergoing endoscopic retrograde cholangiopancreatography for biliary fistula from 2015 to 2021 was conducted at the Endoscospy Unit of Walter Cantídio University Hospital. Clinical characteristics and endoscopic success rates of the post-liver transplantation group were analyzed in comparison with those of other etiologies. RESULTS: The main causes of biliary fistula were liver transplantation (44%) and cholecystectomy complications (44%). The post-liver transplantation group had a significantly higher proportion of male sex (liver transplantation=81.8%, others=28.6%) and older age (liver transplantation=54.1 years, others=42.0 years) and a higher incidence of biliary stenosis (liver transplantation=90.9%, others=14.3%) than those of the group with other etiologies (p<0.05). The two groups received similar treatment types, among which sphincterotomy associated with biliary stent placement was most commonly used. Endoscopic therapeutic success rates showed no significant difference between the post-liver transplantation group (63.6%) and the group with other etiologies (71.4%). CONCLUSIONS: The endoscopic treatment of biliary fistulae secondary to liver transplantation presented a recovery rate similar to that of other etiologies despite the patients older age and the presence of biliary stenosis.

Modulatory Role of Carbon Monoxide on the Inflammatory Response and Oxidative Stress Linked to Gastrointestinal Disorders.

Significance: Carbon monoxide (CO) is an endogenous gaseous mediator that plays an important role in maintaining gastrointestinal (GI) tract homeostasis, acting in mucosal defense, and providing negative modulation of pathophysiological markers of clinical conditions. Recent Advances: Preclinical studies using animal models and/or cell culture show that CO can modulate the inflammatory response and oxidative stress in GI mucosal injuries and pathological conditions, reducing proinflammatory cytokines and reactive oxygen species, while increasing antioxidant defense mechanisms. Critical Issues: CO has potent anti-inflammatory and antioxidant effects. The defense mechanisms of the GI tract are subject to aggression by different chemical agents (e.g., drugs and ethanol) as well as complex and multifactorial diseases, with inflammation and oxidative stress as strong triggers for the deleterious effects. Thus, it is possible that CO acts on a variety of molecules involved in the inflammatory and oxidative signaling cascades, as well as reinforcing several defense mechanisms that maintain GI homeostasis. Future Directions: CO-based therapies are promising tools for the treatment of GI disorders, such as gastric and intestinal injuries, inflammatory bowel disease, and pancreatitis. Therefore, it is necessary to develop safe and selective CO-releasing agents and/or donor drugs to facilitate effective treatments and methods for analysis of CO levels that are simple and inexpensive. Antioxid. Redox Signal. 37, 98-114.

Biliary fistulas associated with liver transplantation versus other etiologies: what is the success rate of the endoscopic treatment? / Fístulas biliares associadas com transplante hepático versus outras etiologias: qual a taxa de sucesso do tratamento endoscópico?

ABSTRACT - BACKGROUND: Biliary fistulas typically occur as surgical complications after laparoscopic cholecystectomy, liver transplantation, or partial liver resection. AIMS: This study aimed to evaluate the efficacy of the endoscopic treatment of biliary fistulae secondary to liver transplantation compared to that of other etiologies. METHODS: A retrospective study of 25 patients undergoing endoscopic retrograde cholangiopancreatography for biliary fistula from 2015 to 2021 was conducted at the Endoscospy Unit of Walter Cantídio University Hospital. Clinical characteristics and endoscopic success rates of the post-liver transplantation group were analyzed in comparison with those of other etiologies. RESULTS: The main causes of biliary fistula were liver transplantation (44%) and cholecystectomy complications (44%). The post-liver transplantation group had a significantly higher proportion of male sex (liver transplantation=81.8%, others=28.6%) and older age (liver transplantation=54.1 years, others=42.0 years) and a higher incidence of biliary stenosis (liver transplantation=90.9%, others=14.3%) than those of the group with other etiologies (p<0.05). The two groups received similar treatment types, among which sphincterotomy associated with biliary stent placement was most commonly used. Endoscopic therapeutic success rates showed no significant difference between the post-liver transplantation group (63.6%) and the group with other etiologies (71.4%). CONCLUSIONS: The endoscopic treatment of biliary fistulae secondary to liver transplantation presented a recovery rate similar to that of other etiologies despite the patients older age and the presence of biliary stenosis

RESUMO - RACIONAL: As fístulas biliares geralmente ocorrem como complicações cirúrgicas, especialmente após colecistectomia laparoscópica, transplante hepático ou ressecção hepática parcial. OBJETIVOS: Avaliar a eficácia do tratamento endoscópico das fístulas biliares secundária ao transplante hepático em comparação com outras etiologias. MÉTODOS: Estudo retrospectivo de 25 pacientes submetidos a Colangiopancreatografia Retrógada Endoscópica por fístula biliar entre 2015 e 2021 no Serviço de Endoscopia do Hospital Universitário Walter Cantídeo. As características clínicas e as taxas de sucesso endoscópico do grupo pós-transplante hepático foram analisadas em comparação com as de outras etiologias. RESULTADOS: As principais causas de fístula biliar foram pós-transplante hepático (44%) e complicações da pós-colecistectomia (44%). O grupo pós-transplante hepático apresentou proporção significativamente maior de sexo masculino (pós-transplante hepático=81,8%, outros=28,6%) e idade mais avançada (pós-transplante hepático=54,1 anos, outros=42,0 anos) e maior incidência de estenose biliar (pós-transplante hepático=90,9%, outros=14,3%) do que o grupo com outras etiologias (p<0,05). Os dois grupos receberam tipos de tratamento semelhantes, dentre os quais a esfincterotomia associada à aposição de prótese biliar foi a mais utilizada. As taxas de sucesso terapêutico endoscópico não mostraram diferença significativa entre o grupo pós-transplante hepático (63,6%) e o grupo com outras etiologias (71,4%). CONCLUSÕES: O tratamento endoscópico das fístulas biliares secundária ao transplante hepático apresentou taxa de recuperação semelhante à de outras etiologias, apesar da idade avançada dos pacientes e da presença de estenose biliar.

Lectin from red algae Amansia multifida Lamouroux: Extraction, characterization and anti-inflammatory activity.

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 ß-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 polysaccharide from Gracilaria caudata reduces hypernociception and inflammatory response during arthritis in rodents.

Polysaccharide from marine alga Gracilaria caudata has potential health benefits, such as anti-inflammatory, gastroprotective and antidiarrheal effects. Here, we investigated the effect of a sulfated polysaccharide from G. caudata (SP-GC) on hypernociception and inflammatory response in arthritis models. The animals received SP-GC (3, 10 or 30 mg/kg) 1 h before tibio-tarsal injection of zymosan. Hypernociception, histopathology, edema, vascular permeability, myeloperoxidase (MPO) activity, cell influx, interleukin (IL)-1ß and nitric oxide (NO) levels were evaluated in acute phase. In another protocol, animals received SP-GC (30 mg/kg) 2 h post-complete Freund's adjuvant (CFA). Hypernociception, edema and arthritis index were determined in acute, sub-chronic and chronic phases. Rota-rod test measured the motor performance. SP-GC significantly reduced, in a dose-dependent manner, the zymosan-induced hypernociception with maximal effect at 30 mg/kg. The microscopic inflammation, joint edema, MPO activity, cell influx, IL-1ß and NO levels were also reduced by SP-GC. In the CFA-induced arthritis, SP-GC inhibits the hypernociception, edema and arthritic index in acute, sub-chronic and chronic phases. SP-GC did not alter the motor performance of animals. In conclusion, SP-GC exerts protective effect in models of arthritis due to the modulation of cell influx, IL-1ß and NO levels, culminating in the reduction of hypernociception and edema.

Gabapentin attenuates intestinal inflammation: Role of PPAR-gamma receptor.

Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and treated them with gabapentin and bisphenol A dicyldidyl ether (PPAR-gamma inhibitor). Macroscopic lesion scores, wet weight, histopathological analysis, mast cell count, myeloperoxidase, malondialdehyde acid, glutathione, nitrate/nitrite, and interleukin levels in the intestinal mucosa were determined. In addition, western blots were performed to determine the expression of Cyclooxygenase-2 (COX-2) and NFκB; Nitric Oxide Inducible Synthase (iNOS) and Interleukin 1 beta (IL-1ß) levels were also determined. Gabapentin was able to decrease all inflammatory parameters macroscopic and microscopic in addition to reducing markers of oxidative stress and cytokines such as IL-1ß and Tumor Necrosis Factor alpha (TNF-α) as well as enzymes inducible nitric oxide synthase and cyclooxygenase 2 and inflammatory genic regulator (NFκB). These effect attributed to gabapentin was observed to be lost in the presence of the specific inhibitor of PPAR-gamma. Gabapentin inhibits bowel inflammation by regulating mast cell signaling. Furthermore, it activates the PPAR-gamma receptor, which in turn inhibits the activation of NFκB, and consequently results in reduced activation of inflammatory genes involved in inflammatory bowel diseases.

Polysaccharide from Gracilaria caudata protects the human esophageal mucosal barrier: A differential topical effect and structural dependence.

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.

LASSBio-596 protects gastric mucosa against the development of ethanol-induced gastric lesions in mice.

LASSBio-596 (2-[4-(1,4-thiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid) is a molecular hybrid of anti-tumor necrosis factor α (TNF-α) and phosphodiesterase 5 inhibitors, and its anti-inflammatory effects have been demonstrated in experimental models of inflammation. The aim of this study was to evaluate the gastroprotective effect of LASSBio-596 in an ethanol-induced acute gastritis model. Before induction of gastric damage, mice were pretreated with LASSBio-596 (20 mg per os (p.o.), Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 3 mg/kg, intraperitoneally [i.p.]) or with 1400W (10 mg/kg, i.p.) given alone or in their combinations. Thirty minutes later, gastric damage was induced by intragastric instillation of 50% ethanol (0.5 ml/25 g, by gavage). After 1 h, gastric damage (hemorrhagic or ulcerative lesions) was measured by planimetry. Samples of the stomach were also taken for histopathological assessment and for assays of tissue myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and inflammatory cytokines. Ethanol administration induced the development of gastric lesions in mice. LASSBio-596 reduced gastric damage, epithelial cell loss and hemorrhage, and restored the antioxidant defense system by decreasing the levels of MDA and the consumption of GSH in gastric mucosa. LASSBio-596 also decreased gastric TNF-α and interleukin-1ß (IL-1ß) protein levels, MPO enzymatic activity, and hemoglobin levels. Treatment with the nitric oxide synthase inhibitors L-NAME and 1400W reversed the effects of LASSBio-596 on ethanol-induced gastric lesions. LASSBio-596 did not alter mucus content and pH of gastric secretions. In summary, LASSBio-596 exerts protective effects against ethanol-induced gastric injury. The gastroprotective effects of LASSBio seem to be NO-dependent.

Gastroprotective effects of N-acylarylhydrazone derivatives on ethanol-induced gastric lesions in mice are dependent on the NO/cGMP/KATP pathway.

The gastroprotective effects of N-acylarylhydrazone derivatives on ethanol-induced gastric lesions in mice were investigated with respect to the NO/cGMP/KATP pathway. To investigate our hypothesis, the mice were intraperitoneally pretreated with glibenclamide, L-NAME, or ODQ 30 min before treatment with DMSO, LASSBio-294 (1, 2, and 4 mg/kg, p.o.), LASSBio-897 (0.5, 1, and 2 mg/kg, p.o.), or omeprazole. After 1 h, the mice received absolute ethanol (4 ml/kg) by gavage to induce gastric mucosal lesions, and the microscopic and macroscopic parameters were evaluated. GSH (non-protein sulfhydryl groups) and MDA (malondialdehyde) concentrations, hemoglobin levels, nitric oxide production, myeloperoxidase (MPO) activity, and TNF-α and IL-1ß levels were also analyzed in the stomach after absolute ethanol administration. Pretreatment with LASSBio-294 or LASSBio-897 significantly reduced the microscopic and macroscopic lesion area. The compounds restored the GSH, MDA, and hemoglobin levels and reduced MPO activity. Moreover, the compounds significantly reduced nitrate and nitrite concentrations in the stomach samples after ethanol administration. Molecular docking studies revealed that LASSBio-294 and LASSBio-897 interact with active sites of the eNOS (endothelial nitric oxide synthase) enzymes through hydrogen bonds. LASSBio-294 and LASSBio-897 also reduced TNF-α and IL-1ß levels. It was observed that a NO synthase inhibitor, an ATP-sensitive potassium channel blocker, and a guanylate cyclase inhibitor significantly reversed the gastroprotective effects of these compounds. Thus, the gastroprotective effect of LASSBio-294 and LASSBio-897 against gastric lesions is mediated through the NO/cGMP cascade, followed by blocking of the KATP channels.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis.

BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

Galactomannan from the seeds of Caesalpinia pulcherrima prevents indomethacin-induced gastrointestinal damage via neutrophil migration.

Galactomannans are neutral polysaccharides isolated from the endosperm of some Leguminosae seeds. They consist of a (1 → 4) linked ß-mannopyranosyl backbone partially substituted at O-6 with α-d-galactopyranosyl side groups. C. pulcherrima have anti-inflammatory and muco-adhesive proprieties. Acute gastritis is an inflammatory disease triggered by use of non-steroidal anti-inflammatory drugs. We investigated the gastroprotective effect of galactomannan obtained from the seeds of Caesalpinia pulcherrima L. (GM-CP) in acute gastritis model induced by indomethacin. Gastritis was induced with indomethacin (30 mg/kg, P.·O.) in female Swiss mice. Animal groups (n = 7) were pretreated with saline-dissolved GM-CP (3 mg/kg, 10 mg/kg, 30 mg/kg, P.O.) or vehicle 1 h before gastritis induction. Mice were euthanized seven hours after the induction. The stomach and blood samples were collected for analysis. At 10 mg/kg, GP-CP reduced the extension of macroscopic lesion and the loss of superficial cells by alleviating inflammatory symptoms (neutrophil infiltration, migration and adhesion of mesenteric leukocytes, production of TNF-α and thiobarbituric acid reactive species (TBARS) and helping to maintain mucin labeling of the tissue. Thus, the findings of the study suggest that GM-CP exhibits gastroprotective effects.

Association between endoscopic findings and histopathological confirmation in patients with suspicion of eosinophilic esophagitis / Associação entre achados endoscópicos e confirmação histopatológica em pacientes com suspeita de esofagite eosinofílica

ABSTRACT BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) is performed by the detection of 15 or more eosinophils per field in an esophageal biopsy sample, but the endoscopic findings alone are not validated for a diagnosis of the disease. OBJECTIVE: To evaluate the association between the endoscopic findings and histopathological diagnosis in patients with suspected EoE in endoscopy. METHODS: A retrospective study of 24 patients with suspicion of EoE during endoscopy was held. The information was collected from databases of Endoscopy and Pathology services of the Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, from March 2012 to April 2018. The patients were divided into a group with positive biopsy (>15 Eosinophils/field, N=8) and a group with negative biopsy (<15 Eosinophils/field, N=16), and the endoscopic findings were compared between the two groups. RESULTS: From a total of 24 patients, 79.1% had longitudinal grooves, 20.8% white exudates, 33.3% mucosal pallor or loss of vascularity and 45.8% had more than one endoscopic finding. There was a significant difference (P<0.05) in the evaluation of the finding of mucosal pallor or decreased vasculature alone among the groups. The positive predictive value and negative predictive value of the presence of more than one endoscopic findings for the diagnosis of EoE was 54% and 84%, respectively. CONCLUSION: There was a low association between the presence of endoscopic findings and histopathological confirmation of the disease, which indicates that endoscopic findings alone are not reliable for the diagnosis of EoE.

RESUMO CONTEXTO: O diagnóstico da esofagite eosinofílica é realizado através da detecção, em amostra de biópsia esofágica, de 15 ou mais eosinófilos por campo, sendo que os achados endoscópicos isolados não são validados para o diagnóstico da doença. OBJETIVO: Avaliar a associação entre os achados endoscópicos com o diagnóstico histopatológico em pacientes com suspeita de esofagite eosinofílica na endoscopia. MÉTODOS: Estudo retrospectivo de 24 pacientes com suspeita de esofagite eosinofílica durante endoscopia digestiva alta. As informações foram colhidas de bancos de dados dos serviços de Endoscopia e Patologia do Hospital Universitário Walter Cantídio da Universidade Federal do Ceará, no período de março de 2012 a abril de 2018. Os pacientes foram divididos em grupo com biópsia positiva (>15 eosinófilos/campo, N=8) e grupo com biópsia negativa (<15 eosinófilos/campo, N=16), sendo comparados os achados endoscópicos entre os dois grupos. RESULTADOS: Do total de 24 pacientes, 79,1% tinham a presença de sulcos longitudinais, 20,8% exsudatos brancos, 33,3% palidez de mucosa ou perda da vascularização e 45,8% apresentaram mais de um achado endoscópico. Houve diferença significativa (P<0,05) na avaliação do achado de palidez ou perda da vascularização, isoladamente, entre os grupos. O valor preditivo positivo e valor preditivo negativo da presença de mais de um achado endoscópico para o diagnóstico de esofagite eosinofílica foi de 54% e 84%, respectivamente. CONCLUSÃO: Houve uma baixa associação entre a presença de achados endoscópicos e a confirmação histopatológica da doença, o que faz com que os achados endoscópicos isolados não sejam confiáveis para o diagnóstico de esofagite eosinofílica.

Gastroduodenal Symptoms in Inflammatory Bowel Disease Are Correlated with Gastric Emptying and Serum Levels of Active Ghrelin.

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.