Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination

ABSTRACT Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Erosive esophagitis secondary to radiotherapy: Case report / Esofagitis erosiva secundaria a radioterapia: reporte de un caso

Abstract Introduction: Erosive esophagitis secondary to radiotherapy is an unusual complication in the oncological treatment of thoracic tumors. This pathological entity is associated with multiple complications, which is a clinical challenge for health workers unfamiliar with the clinical manifestations. Clinical case: A 64-year-old woman with a 3-day clinical picture of chest pain radiating to the epigastrium with 10/10 intensity. On physical examination, she was tachycardic, hypotensive, and with intense pain in the upper hemiabdomen region; she had no signs of peritoneal irritation on deep palpation. Paraclinical tests showed no signs of local or disseminated infection, but endoscopy of the digestive tract reported post-radiation esophagitis. Discussion: Erosive esophagitis after radiotherapy occurs in less than 1 % of cases, and clinical manifestations such as dysphagia, odynophagia, and abdominal pain are common. Initial symptomatic management is preserved, with supportive measures such as intravenous hydration and proton pump inhibitors (PPIs). In case of intolerance to the oral route, therapy with nutritional support is indicated via nasogastric tube or gastrostomy in the most severe cases.

Resumen Introducción: la esofagitis erosiva secundaria a la radioterapia es una complicación inusual del tratamiento oncológico de los tumores torácicos. Esta entidad patológica está asociada con múltiples complicaciones, lo que resulta un reto clínico para los profesionales en salud que están poco familiarizados con las manifestaciones clínicas. Caso clínico: mujer de 64 años con cuadro clínico de 3 días de dolor torácico irradiado al epigastrio con intensidad 10/10. En el examen físico se encontró taquicárdica, hipotensa, con dolor intenso en la región hemiabdominal superior; a la palpación profunda no tenía signos de irritación peritoneal. Los paraclínicos no mostraron signos de infección local o diseminada, pero la endoscopia de vías digestivas reportó esofagitis posirradiación. Discusión: la esofagitis erosiva posterior a la radioterapia se presenta en menos del 1 % de los casos, las manifestaciones clínicas como disfagia, odinofagia y dolor abdominal son frecuentes; el manejo sintomático inicial es conservado, con medidas de soporte como hidratación intravenosa e inhibidores de la bomba de protones (IBP). En caso de intolerancia a la vía oral se indica terapia con soporte nutricional por sonda nasogástrica o gastrostomía en los casos más graves.

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Enema de sulcralfato pode prevenir colite em segmentos colônicos sem trânsito fecal? / Can sucralfate enema prevent colitis in colonic segments without fecal transit?

RESUMO - RACIONAL: O estresse oxidativo é um dos principais mecanismos associados à ruptura dos mecanismos de defesa que formam a barreira epitelial cólica e reduz o conteúdo tecidual das proteínas claudina-3 e ocludina principais constituintes das junções de oclusão intercelulares. O sucralfato, possui atividade antioxidante e tem sido usado para tratar diferentes formas de colite. OBJETIVO: Mensurar o conteúdo tecidual de claudina-3 e ocludina da mucosa do cólon sem trânsito fecal, submetido à intervenção com sucralfato. MÉTODO: Trinta e seis ratos foram submetidos à colostomia do cólon esquerdo e fístula mucosa distal. Os animais foram divididos em dois grupos de acordo com a eutanásia ser realizada duas ou quatro semanas após a intervenção. Cada grupo foi dividido em três subgrupos de acordo com o tipo de intervenção realizada diariamente: solução salina isolada; sucralfato a 1 g/kg/dia ou sucralfato a 2g/kg/dia. A colite foi diagnosticada por análise histológica adotando escala de validação prévia. A expressão tecidual de ambas as proteínas foi identificada por imunoistoquímica. O conteúdo das proteínas foi quantificado por análise de imagem assistida por computador. RESULTADOS: O escore inflamatório foi maior nos segmentos cólicos sem trânsito fecal e os enemas com sucralfato reduziram o escore inflamatório nesses segmentos, principalmente nos animais submetidos à intervenção com sucralfato em maior concentração e por período mais longo de intervenção. Houve aumento no conteúdo tecidual das proteínas claudina-3 e ocludina, relacionado com a concentração de sucralfato. O conteúdo tecidual de ambas as proteínas não se modificou com a duração da intervenção. CONCLUSÃO: Enemas com sucralfato reduzem a inflamação e aumentam o conteúdo tecidual de claudina-3 e ocludina na mucosa cólica sem trânsito intestinal.

ABSTRACT - BACKGROUND: Oxidative stress is one of the main mechanisms associated with the rupture of the defense mechanisms of the colonic epithelial barrier; it reduces the tissue content of the claudin-3 and occludin proteins, which are the main constituents of intercellular tight junctions. Sucralfate (SCF) has antioxidant activity and has been used to treat different forms of colitis. AIM: This study aimed to measure the tissue claudin-3 and occludin content of the colon mucosa without fecal transit, subjected to intervention with SCF. METHODS: Thirty-six rats were subjected to left colon colostomy and distal mucous fistula. They were divided into two groups according to euthanasia that was performed 2 or 4 weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone, SCF at 1 g/kg/day, or SCF at 2 g/kg/day. Colitis was diagnosed by the histological analysis adopting the previous validate scale. The tissue expression of both proteins was identified by immunohistochemical technique. The content of proteins was quantified by computer-assisted image analysis. RESULTS: The inflammatory score was high in colonic segments without fecal transit, and enemas with SCF reduced the inflammatory score in these segments, mainly in those animals submitted to intervention with SCF in greater concentration and for a longer period of intervention. There was an increase in tissue content of claudin-3 and occludin, related to SCF concentration. The tissue content of both proteins was not related to the intervention time. CONCLUSION: Enemas with SCF reduced the inflammation and increased the tissue content of claudin-3 and occludin in colonic mucosa without fecal stream.

Efficacy and Safety of AlbisD Compared With Omeprazole 20 mg in Patients With Non-erosive Reflux Disease: A Randomized, Open-label, Active-controlled, Pilot Study

BACKGROUND/AIMS: Proton pump inhibitors (PPIs) are frequently used to treat non-erosive reflux disease (NERD), but their effect is limited. It is not known whether a potential alternative, AlbisD, containing ranitidine hydrochloride, sucralfate hydrate, and tripotassium dicitrato bismuthate, is effective and safe in treating NERD. The aim of the study is to evaluate the efficacy and safety of AlbisD compared with omperazole in patients with NERD. METHODS: This was a multicenter, randomized, open-label, parallel-group, non-inferiority comparative study. A total of 126 patients with NERD were randomly allocated to either AlbisD twice daily or omeprazole 20 mg once daily for 4 weeks from February 2016 to August 2016. The study patients had histories of heartburn or regurgitation of moderate severity (> score 2) and a frequency of at least 2 episodes per week, and had no mucosal breaks of the esophagus on endoscopy. The primary efficacy variable was complete cure of heartburn at week 4. Secondary efficacy variables evaluating symptoms of heartburn and acid reflux as well as safety profiles were compared in the 2 groups at week 2 and 4 after treatment. RESULTS: A total of 113 patients completed the study (57 and 56 in AlbisD and omeprazole groups, respectively). The proportion of patients with complete cure of heartburn at week 4 was not significantly different between the AlbisD and omeprazole groups (35.1% vs 32.1% respectively, P = 0.740). There were no significant differences between the 2 groups in the any secondary variables including proportions of days without heartburn or acid reflux over 4 weeks (including daytime and nighttime). Adverse events were similarly reported in the 2 groups (7 [12.3%] vs 6 [10.7%]), and there were no serious adverse events. CONCLUSIONS: The efficacy and safety of AlibsD in treating NERD patients are not inferior to those of omeprazole. Therefore, AlbisD can be an alternative to PPIs for NERD.

Evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / Avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

[retracted article]: evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / [artigo retratado]: avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

Effect of sucralfate on cytokines in rat with paraquat poisoning / 中华危重病急救医学

Objective To explore the effect of sucralfate on cytokines in rats with paraquat (PQ) poisoning. Methods Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into PQ model group, sodium bicarbonate intervention group (SB group) and sucralfate suspension gel group (LTL group), with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL·kg-1·d-1of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline. The abdominal aortic blood of rats was collected at 1, 3, 6, and 10 days after PQ poisoning, and the levels of serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA). The left lung tissue was harvested, and lung wet/dry weight (W/D) ratio was assessed. Results With prolonged exposure, lung W/D ratios in all the groups were increased gradually, reached the peak at 10 days, but in the SB group and LTL group, the amplitude of increase was obviously reduced, the ratios were significantly decreased at 6 days and 10 days as compared with those in PQ model group (SB group vs. PQ model group: 4.99±0.79 vs. 6.98±0.86 at 6 days, 5.61±0.36 vs. 7.36±0.95 at 10 days; LTL group vs. PQ model group: 4.61±0.24 vs. 6.98±0.86 at 6 days, 4.24±0.20 vs. 7.36±0.95 at 10 days, all P < 0.05), but there was no significant difference between SB group and LTL group (all P > 0.05). After PQ poisoning, the levels of TNF-α, IL-10 and TGF-β1 were elevated, and reached the peak at 3 days and then decreased gradually. Compared with the PQ model group, serum TNF-α, IL-10 and TGF-β1 levels in SB group and LTL group were decreased significantly [SB group vs. PQ model group: 3-day TNF-α (ng/L) was 147.6±12.3 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 65.4±3.2 vs. 115.1±9.2, 3-day TGF-β1 (ng/L) was 356.3±50.3 vs. 415.6±68.3; LTL group vs. PQ model group: 3-day TNF-α (ng/L) was 82.2±7.4 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 44.4±5.2 vs.115.1±9.2, 3-day TGF-β1 (ng/L) was 296.3±40.2 vs. 415.6±68.3, all P < 0.05], especially in LTL group (all P < 0.05). Conclusion Early gastrointestinal lavage with sucralfate could effectively reduce the inflammatory exudation in lung tissue after PQ poisoning, and inhibit the cytokine secretion.

Evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / Avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método : Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

Elimination of unplanned treatment breaks and dose reductions caused by mucositis: Positive implications for survival outcomes and cost reductions using high potency polymerized cross-linked sucralfate in 55 patients undergoing radiation for head and neck cancer with and without chemotherapy

PURPOSE: Annually 27,855 patients in Korea develop treatment-induced mucositis nearly doubling the cost of cancer care. It is an emergency medical condition causing unplanned treatment breaks in 4,998 patients. The subsequent reduction in optimal dose-intensity causes premature deaths due to lower 5-year survival. An additional 216 patients die from mucositis-mediated sepsis and infection. Thus complete elimination of mucositis will immediately reduce the cost of care while simultaneously eliminating 5,214 mucositis-associated deaths. High potency polymerized cross-linked sucralfate (HPPCLS) cleared by the US Food and Drug Administration has been associated with the elimination of mucositis.METHODS: Observational, self-reporting, practice-based mucositis registry. Inclusion criteria: any patient with chemoradiation-induced mucositis. Exclusion criteria: previous adverse reaction to sucralfate products. Primary outcome: rapid reversal or complete prevention. Conduct of study: 28 radiation oncologists from 21 different institutions prescribed HPPCLS to 55 patients undergoing chemoradiation for squamous cell carcinoma of head and neck and esophagus to eliminate mucositis-associated treatment breaks.RESULTS: All patients with World Health Organization grade 1 (n=6), grade 2 (n=23), grade 3 (n=16) oral mucositis, and grade 2 esophageal mucositis (n=2) experienced complete reversal of mucositis. Within 2–3 days both mucosa and swallowing normalized. Anticipated grade 3/4 mucositis was prevented in 8 out of 8 elderly patients aged 78–93 avoiding gastrostomy tube placement. Statistical analysis of outcomes: Outcomes qualified as a positive Glasziou treatment effect that was statistically significant (P<0.05).CONCLUSION: HPPCLS eliminated mucositis by rapid reversal or complete prevention, thereby eliminating unplanned treatment breaks. It may likely reduce mucositis-associated increased cost of care and premature deaths.

Effects of corn oil on the volatile fatty acids in horses with induced gastric ulcers / Efecto del aceite de maíz sobre los ácidos grasos volátiles en caballos con úlceras gástricas inducidas

ABSTRACT Objetive. To determine the influence of corn oil on the volatile fatty acids (VFA) concentrations in the gastric juice in horses with phenylbutazone (PBZ) induced gastric ulcers and Correlate the gastroscopic findings with the VFA concentrations. Materials and methods. 15 horses were allotted in 3 groups. Group I (control) received placebo during first 6 days (induction period) and was treated with sucralfate for 2 weeks (treatment period). Groups II and III received PBZ during the induction phase. After 6 days, horses from group II received 70 mL of corn oil /100 kg of body weight/ po, twice a day, for 2 weeks and horses from group III received 90 mL of corn oil/100 kg of body weight/ po, twice a day, for 2 weeks. All horses were examined by gastroscopy at days 0, 7 and 21. The lesions were recorded and classified according to the number and severity. Samples from gastric fluid were taken to measure the concentrations of the acetic, propionic, butyric and lactic acids. Results. Both PBZ protocols produced lesions in the both non-glandular and glandular areas of the stomach. All the treatments produced healing of the injured mucosa glandular. Neither of the two corn oil treatments affected healing of the gastric ulcers located in the non-glandular area. Conclusions. The concentrations of acetic and butyric acids were highest in the gastric juice. The corn oil and sucralfate did not lead to differences in the concentration of acetic acid and butyric acid.

RESUMEN Objetivo. Determinar el efecto del aceite de maíz sobre la concentración de los ácidos grasos volátiles (AGV) en el jugo gástrico de caballos con úlceras gástricas inducidas con fenilbutazona (FBZ) y correlacionar los hallazgos gastroscópicos con las concentraciones de AGV. Materiales y métodos. 15 caballos fueron asignados en 3 grupos. El grupo I (control) recibió placebo durante los primeros 6 días (período de inducción) y fue tratado con sucralfato durante 2 semanas (período de tratamiento). Los grupos II y III recibieron FBZ en la fase de inducción. Después de 6 días, los caballos del grupo II recibieron 70 ml de aceite de maíz /100 kg de peso corporal / vo, dos veces al día, durante 2 semanas y los caballos del grupo III recibieron 90 ml de aceite de maíz / 100 kg de peso corporal / vo, dos veces al día, durante 2 semanas. Todos los caballos fueron examinados por gastroscopia en el día 0, 7 y 21. Las lesiones fueron registradas y clasificadas según el número y severidad. Muestras de fluido gástrico se utilizaron para medir las concentraciones de los ácidos acético, propiónico, butírico y láctico. Resultados. Ambos protocolos de FBZ ocasionaron lesiones en las áreas aglandular y glandular del estómago. Todos los tratamientos reestablecieron el epitelio ulcerado de la mucosa glandular. Ninguno de los dos tratamientos a base de aceite de maíz reestablecieron el epitelio ulcerado de la zona aglandular del estómago. Conclusiones. Las concentraciones de los ácidos acético y butírico fueron más altas en el jugo gástrico. El aceite de maíz y el sucralfato no afectaron la concentración de ácido acético y ácido butírico.

Actual duration of patient-reported mucositis: Far longer than 2 to 4 weeks and may be avoidable altogether

The impression that oral mucositis is a brief 14–28 day-consequence of chemoradiation is misguided. Clinically significant patient-reported oral mucositis may last 46 to 102 days depending on the treatment schedule and the modality used. The process of mucositis can occur in the epithelium throughout the entire GI tract and may possibly be avoided with the prescribed use of high potency polymerized cross-linked sucralfate (HPPCLS). Literature review of patient-reported mucositis occuring in the three common schedules of cancer treatment administration: daily radiation therapy, induction-based hematopoietic stem cell transplantation (HSCT), and multi-cycle chemo/immunotherapy (CT-IT). Review articles published in last 15 years focused on treatment-induced oral mucositis. The author reviewed 56 articles published in 15 years from 1999–2014 that focused primarily on treatment-induced oral mucositis. Only 6 were found to meet the criteria of providing patient-reported data from the beginning, throughout and following cancer treatment. For HSCT, radiation therapy, and CT-IT, despite active anti-mucositis treatment, patient-reported oral mucositis lasted 46–60 days, 70–84 days, and 68–102 days, respectively. Mucositis caused by cancer treatment, regardless of modality, lasts far longer than the oft quoted 2–4 weeks (range, 14–28 days). Patient reported mucositis persists from 46 to 102 days. This patient-based experience is the primary cause of treatment interruptions, delays or cancellations. It may be avoidable with HPPCLS that both prevents and rapidly reverses mucositis anywhere it occurs within the gastrointestinal tract.

Evaluation of the anti-inflammatory and antioxidant effects of the sucralfate in diversion colitis / Avaliação dos efeitos anti-inflamatório e antioxidante do sucralfato na colite de exclusão

Objective: To evaluate the anti-inflammatory and antioxidant effects of sucralfate enemas in diversion colitis model. Method: Thirty-six Wistar rats underwent intestinal bypass by end colostomy in the descending colon and distal mucous fistula. The animals were divided into 3 experimental groups according to the daily dose of enemas received containing 0.9% SF, sucralfate enemas or sucralfate enemas 1 g/kg/day or 2 g/kg/day. Each group was divided into two subgroups according to euthanasia to be performed 2-4 weeks after derivation. The tissue grade of inflammation was assessed histologically, and neutrophil infiltration by the tissue expression of myeloperoxidase (MPO) identified by immunohistochemistry and quantified by computerized morphometry. Oxidative stress was measured by tissue levels of malondialdehyde (MDA). To compare the results the Student's t test variance was used, and also the variance by ANOVA test, establishing a level of significance of 5% (p< 0.05) for both. Results: The intervention with sucralfate enemas showed improvement in the intensity of tissue inflammation related to the concentration used and the duration of the intervention. Intervention with sucralfate enemas reduced the tissue levels of MPO, independent of concentration or time of intervention (p< 0.01). There was a reduction of MDA levels in animals irrigated with sucralfate enemas, independent of concentration or duration of the intervention (p< 0.01). Conclusion: Enemas with sucralfate enemas reduce inflammation, neutrophil infiltration and oxidative stress in the excluded colon suggesting topical application of the substance to be a valid therapeutic option for the treatment of diversion colitis. (AU)

Objetivo: Avaliar os efeitos anti-inflamatórios e antioxidantes do SCF em modelo de colite de exclusão. Método: Trinta e seis ratos, foram submetidos a derivação intestinal por colostomia terminal no cólon descendente e fistula mucosa distal. Os animais foram divididos em 3 grupos experimentais segundo receberem clisteres diários com SF 0,9%, SCF 1 g/kg/dia ou SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos segundo a eutanásia ser realizada após 2 ou 4 semanas da derivação. O grau de inflamação tecidual foi avaliado por estudo histológico e a infiltração neutrofílica pela expressão tecidual de mieloperoxidase (MPO) identificada por imunoistoquímica e quantificada por morfometria computadorizada. O estresse oxidativo foi mensurado pelo conteúdo de malondialdeído (MDA). Para análise dos resultados utilizou-se os teste t de Student, e ANOVA, estabelecendo-se para todos os testes nível de significância de 5% (p< 0,05). Resultados: A intervenção com SCF melhorou o grau de inflamação tecidual relacionando-se a concentração utilizada e ao tempo de intervenção. A intervenção com SCF reduziu os níveis teciduais de MPO, independente da concentração ou do tempo de intervenção (p< 0,01). Houve redução dos níveis de MDA nos animais irrigados com SCF, independente da concentração ou tempo de intervenção (p< 0,01). Conclusão: Enemas com SCF reduzem o processo inflamatório, infiltrado neutrofílico e estresse oxidativo no cólon excluso sugerindo que a substância possa se tornar uma opção terapêutica válida para o tratamento da colite de exclusão. (AU)

Tissue content of sulfomucins and sialomucins in the colonic mucosa, without fecal stream, undergoing daily intervention with sucralfate

PURPOSE: To measure the content of acidic mucin, sialomucin, and sulfomucins in the colonic mucosa without fecal stream submit to intervention with sucralfate (SCF). METHODS: Thirty-six rats were submitted to a right colostomy and a distal mucous fistula and divided into two groups according to sacrifice to be performed two or four weeks. Each group was divided into three subgroups according daily application of enemas containing saline, SCF at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis. Acid mucins were determined with the Alcian-Blue and sulfomucin and sialomucin by high iron diamine-alcian blue (HID-AB) techniques. The mucins were quantified by computer-assisted image analysis. Mann-Whitney and ANOVA tests were used to analyze the results establishing the level of significance of 5% for both (p<0.05). RESULTS: SCF enemas decreased the inflammation score and was related to the concentration used and time of the intervention. SCF at both concentrations increased the content of acid mucin, which was related to the concentration used and to the improvement in the inflammatory score. There was an increase in the content of sulfomucins and sialomucins in SCF groups. SCF increased sulfomucins from 2 weeks of intervention, which was not related to the dose or time of application. The increase in sialomucin content was related to the time and dose used in the intervention. CONCLUSION: Sucralfate increased the content of acidic mucins, primarily at the expense of sialomucin, which was affected by the dose and time of intervention. .

A 66 Patient Multi-Institution Phase IV Post-Authorization Surveillance of ProThelial™ (High Potency Polymerized Cross-linked Sucralfate) -Single Agent Efficacy for the Prevention and Rapid Reversal of Chemo-radiation Induced Oral, Esophageal and Intestinal Mucositis.

Background: Standard potency sucralfate is not recommended by most clinical guidelines for prevention or treatment of oral and intestinal mucositis. However, its polymerized cross-linked (thereby high potency) formulation (HPPCLS) was cleared by the FDA for management of oral mucositis and has been associated with complete prevention and rapid reversal of oral, esophageal and intestinal mucositis. Statistically significant high quality evidence from a 66 patient multi-institution phase IV non-controlled observation study is reported here. Patients and Methods: In February 2014, as part of the Phase IV post-approval surveillance of HPPCLS, a non-interventional mucositis registry was established. The primary aim of the registry was the surveillance of patients’ tolerance of HPPCLS. A secondary aim was the observation of the prescribing pattern of oncologists using HPPCLS to manage chemo-radiation induced mucositis. Inclusion Criteria: Any cancer treatment patient who developed or was anticipated to develop oral mucositis and was prescribed HPPCLS. Exclusion Criteria: Allergies or prior adverse reactions to sucralfate. Conduct of Study: Patients identified by oncology clinical staff with mucositis or anticipated to develop mucositis, were prescribed a 75 ml single week-supply of HPPCLS as needed. Results: Thirty-nine oncologists from 32 institutions prescribed HPPCLS to 66 patients. No adverse reactions were reported. Five patients were lost to follow-up and 61 patients reported outcomes. Eight patients experienced successful prevention of mucositis averting placement of gastrostomy tube and the remaining 53 patients with WHO-Grade 1-3 mucositis involving the mouth, esophagus, small bowel & colon experienced reversal in 2-3 days. Though cleared for oral use only, 48 of 61 patients were instructed by oncologists to swallow HPPCLS following swish-and-gargle. Statistical Analysis: Quantitative Glasziou rate-ratio treatment effect beyond 10 (37-82 for HPPCLS) supported efficacy (p≤0.05). Conclusion: HPPCLS paste may offer oncologists a single-agent approach to manage chemo-radiation induced mucositis. To wit a protocol is offered for practical use.

Effects of pH on the suspension gel formation and free aluminum ions of sucralfate / 中国药学杂志

OBJECTIVE: To investigate the effect of antacids on the efficacy and safety of sucralfate. METHODS: The appearance of sucralfate suspension gel was observed under different pHs in vitro to learn the appropriate pH for sucralfate to work. The adverse effects of sucralfate was evaluated by determining the aluminum ion concentration in the supernatant using emission spectrometry with inductively coupled plasma (ICP-OES). RESULTS: At pH 0.1, sucralfate was partly dissolved; at pH 1.0 and 2.0, it formed white soft gel with strong adhesion and good extension; along with the storage time, the gel gradually precipitated; at pH≥3, sucralfate was unable to form gel; at pH >4.0, it formed a hard white precipitate without obvious adhesion and spreadability. In the pH range of 0.1-7.0, the concentration of free aluminum ion reduced gradually with the increase of pH. CONCLUSION: Combination use of antacids with sucralfate does not increase the aluminum ion absorption, but whether there is a synergistic effec is worth of further exploration.

Treatment of Helicobacter pylori infection mice with Anti-H. pylori rFlaA IgY-sucralfate EC microcapsules / 中国药学杂志

OBJECTIVE: To investigate the efficacy of Anti-H. pylori rFlaA IgY-sucralfate ethyl cellulose(EC) microcapsules on Helicocacter pylori infection in mice. METHODS: After dealing with sucralfate, the rFlaA IgY microcapsules were prepared with EC by organic solvent evaporation method. The protective effect of sucralfate at different concentrations of pepsin in different pH on the rFlaA IgY activity was also evaluated. Treating the mice with the microcapsules by oral at various dosages (0.8, 1.6, 3.2 and 6.4 mg · g-1 · d -1), the anti- H. pylori serum of the mice and the urease of the gastric mucosa were detected to evaluate the clearance rate of H. pylori by ELISA and rapid urease test. RESULTS: The results showed that under simulated gastric juice with common pepsin concentration (0.02 mg · mL-1), the relative activity of the IgY treated with 40% sucralfate can maintain 82.14% for 8 h at pH 3.0 and 63.28% at pH 2.0, it can only keep 21.52% at pH 1.0. While under the simulated gastric juice with high pepsin concentration (0.04 mg · mL-1), the relative activity of the IgY can maintain 77.87% with 40% sucralfate at pH 3.0, 57.76% at pH 2.0 and 22.79% at pH 1.0. The entrapment efficiency of the EC microcapsules was 83.79%. The release rate of the EC microcapsules was 95.92% in 5 h. After treatment with rFlaA IgY EC microcapsules, the levels of anti-H. pylori antibody were significantly decreased in each group. The clearance rate of H. pylori at dosage of 3.2 mg · g-1 · d-1 was 80%, the rFlaA IgY at dosage of 6.4 mg · g-1 · d-1 can completely clear the H. pylori in mice gastric mucosa. CONCLUSION: The 40% sucralfate can protect IgY in the simulated gastric juice. The rFlaA IgY EC microcapsules have high entrapment efficiency and sustained-release effect in vitro as well as good clearance effect of H. pylori infection by oral administration.

Treatment of Helicobacter pylori-infected gastritis in BALB/c mice by HP1188-IgY / 中国病理生理杂志

AIM:To evaluate the effects of treatment with HP 1188-immunoglobulin yolk ( HP1188-IgY) on Helicobacter pylori ( H.pylori)-infected gastritis in BALB/c mice.METHODS:BALB/c mice were used to establish an animal model of H.pylori-infected gastritis, and the mice were divided into 8 groups (10 mice per group).Oral antibiotics were used in group 1, 1 mg HP1188-IgY in group 2, 1 mg HP1188-IgY plus 30%sucralfate in group 3, 5 mg HP1188-IgY in group 4, 5 mg HP1188-IgY plus 30%sucralfate in group 5, PBS in group 6, and 30% sucralfate in group 7 with the treatment once per day for 10 d;and 2.5 mg HP1188-IgY was injected hypodermically twice with a 48-h interval in group 8.Another 10 mice were used as normal control in group 9.The planting of bacteria in the stomach was assayed by bacteri-al culture, rapid urease test, PCR and pathological sectioning .RESULTS:Intragastric administration with 1 mg HP1188-IgY plus 30%sucralfate per day effectively cured the injury of gastric mucosa caused by H.pylori infection, and the effect has no significant difference compared with antibiotics (P>0.05).CONCLUSION:We establish a BALB/c mouse mod-el infected with H.pylori successfully.Sucralfate (30%) is an ideal protectant for HP1188-IgY, which might decrease H. pylori infection in the stomach of BALB/c mice by oral inoculation .

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

PURPOSE: To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS: Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS: Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins. The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS: Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream. .

Effects of sucralfate and acid-suppressive drugs on preventing ventilator-associated pneumonia of mechanically ventilated patients: a meta-analysis / 中华内科杂志

Objective To evaluate the effect of sucralfate and acid-suppressive drugs on preventing ventilator-associated pneumonia (VAP) in mechanically ventilated patients.Methods All randomized controlled trials (RCTs),which studied the effect of sucralfate and acid-suppressive drugs on the incidence of VAP in mechanically ventilated patients,were searched from PubMed,Embase and the Cochrane Library during January 1966 to March 2013 via manual and computer retrieval.All related data were extracted.Meta analysis was conducted using the statistical software RevMan 5.2 and the quality of the RCTs was strictly evaluated with the methods recommended by the Cochrane Collaboration.Results A total of 15 RCTs involving 1315 patients in the sucralfate group and 1568 patients in the acid-suppressive drug group were included in this study.The incidence of VAP was significantly reduced in the sucralfate group (RR =0.81,95％ CI 0.7-0.95,P =0.008),while no difference was found between the two groups in the incidence of stress-related gastrointestinal bleeding (RR =0.96,95％ CI 0.59-1.58,P =0.88).No statistical difference was found in the days on ventilator,duration of ICU stay and ICU mortality in the two groups (all P values ＞ 0.05).Conclusion In patients with mechanical ventilation,sucralfate could decrease the incidence of VAP,while has no such effect on the stress-related gastrointestinal bleeding,the days on ventilator,duration of ICU stay and ICU mortality.