Protective effect of against ethanol-induced gastric ulcer and its mechanism / 浙江大学学报·医学版

: To investigate the protective effect of (FD) against ethanol-induced gastric ulcer and its mechanism. : Human gastric epithelial GES-1 cells were divided into normal control group, model control group, FD 95% alcohol extract group, FD 50% alcohol extract group and FD decoction extract group. Gastric ulcer was induced by treatment with 1% ethanol in GES-1 cells. The cell proliferation was detected with MTT method in each group. Sixty SD rats were randomly divided into normal control group, model control group, ranitidine group and low-dose, medium-dose, high-dose FD 95% alcohol extract groups (150, 300, 600 mg/kg). The corresponding drugs were administrated by gavage for The gastric ulcer model was induced by intragastric administration of anhydrous ethanol. The gastric ulcer area and ulcer inhibition rate of rats were measured in each group; the degree of gastricmucosal damage was observed by scanning electron microscopy; the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) in gastric tissues were detected by ELISA method. : 95% alcohol extract of FD had the strongest protective effect on proliferation of GES-1 cells. In animal experiments, compared with the normal control group, a large area of ulcers appeared on the gastric mucosa in the model control group, while the ulcer areas of the FD groups and ranitidine group were significantly smaller than that of the model control group (all <0.05). Compared with the model control group, FD groups and ranitidine group significantly reduced the levels of TNF-α, IL-1β, IL-6 in serum and the MDA content in the gastric tissues, and increased the activity of SOD, CAT and GSH in gastric tissues (all <0.05). : The 95% alcohol extract of FD can reduce the levels of TNF-α, IL-1β and IL-6 in serum and the content of MDA in gastric tissues, and increase the activity of SOD, CAT and GSH in gastric tissues to achieve the protective effect against gastric ulcer.

The Protective Effect of Lercanidipine on Indomethacin-Induced Gastric Ulcers in Rats

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.

Perfil fitoquímico e atividade gastroprotetora dos frutos de Eugenia mattosii / Phytochemical profile and gastroprotective activity of eugenia mattosii fruits

ABSTRACT BACKGROUND: Extracts obtained from plants and fruits provide a relatively safe and practical alternative for the conventional medicine of gastrointestinal diseases. The specie Eugenia mattosii, popularly known in Brazil as "cerejinha", belongs to Myrtaceae family. Species of this family present pharmacological properties, and can be used in the treatment of gastrointestinal disorders. OBJECTIVE: The aim of this study was to determine the phytochemical profile and evaluate the gastroprotective activity of Eugenia mattosii fruits. METHODS: Phytochemical analysis was carried out by thin layer chromatography and gastroprotective assays were performed using two experimental models: acute ulcer model induced by ethanol/HCl and acute ulcer model induced by non-steroidal anti-inflammatory drug (indomethacin). Total lesion area (mm2) and relative lesion area (%) were determined. RESULTS: The results of the phytochemical analysis indicated that the bark and pulp and seeds of E. mattosii present phenolic compounds, terpenes and/or steroids. In gastric ulcer model induced by ethanol was evidenced significant reduction of damaged areas for doses of 50 and 250 mg/ kg of seeds methanol extract, while in the indomethacin-induced ulcer model, all parts of the fruit presented defense capability of the gastric mucosa by reducing lesions at doses of 50, 125 and 250 mg/kg. CONCLUSION: The results demonstrate that the specie E. mattosii has bioactive compounds that provide gastroprotective activity, presenting possible therapeutic potential.

RESUMO CONTEXTO: Extratos obtidos de plantas e frutos fornecem uma alternativa relativamente segura e prática para os remédios convencionais de doenças gastrointestinais. A espécie Eugenia mattosii, popularmente conhecida no Brasil como "cerejinha", pertence à família Myrtaceae. Espécies desta família apresentam propriedades farmacológicas e podem ser utilizadas no tratamento de distúrbios gastrointestinais. OBJETIVO: O objetivo deste estudo foi determinar o perfil fitoquímico e avaliar a atividade gastroprotetora dos frutos de Eugenia mattosii. MÉTODOS: A análise fitoquímica foi realizada por cromatografia em camada delgada e dois modelos experimentais foram utilizados para avaliação da atividade gastroprotetora em camundongos: modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl. RESULTADOS: Os resultados da análise fitoquímica indicaram que a casca e polpa e as sementes de E. mattosii apresentam compostos fenólicos, terpenos e/ou esteroides. No modelo de úlcera gástrica induzido pelo etanol, foi evidenciada redução significativa de áreas danificadas para doses de 50 e 250 mg/kg do extrato das sementes, enquanto no modelo de úlcera induzida por indometacina, todas as partes do fruto apresentaram capacidade de defesa da mucosa gástrica ao reduzir as lesões nas doses de 50, 125 e 250 mg/kg. CONCLUSÃO: Os resultados demonstram que a espécie E. mattosii possui compostos bioativos com atividade gastroprotetora, apresentando possível potencial terapêutico.

Screening of wild fruit trees with gastroprotective activity in different experimental models / Triagem de plantas frutíferas silvestres com ação gastroprotetora em modelos in vivo

ABSTRACT BACKGROUND Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. OBJECTIVE The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. METHODS The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. RESULTS The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. CONCLUSION It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.

RESUMO CONTEXTO Devido ao aumento de pessoas com distúrbios gastrointestinais, a busca de tratamentos alternativos com menos efeitos cola­terais é fundamental, assim como a demanda por alimentos ou plantas que possam ajudar a proteger o estômago. OBJETIVO O presente estudo teve como objetivo avaliar a ação gastroprotetora dos extratos plantas frutíferas silvestres Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) e Marlierea tomentosa Cambess. (guarapuruna) em modelos farmacológicos in vivo. MÉTODOS As diferentes partes do fruto foram submetidas se­paradamente a um processo de maceração em solução metanólica a frio. Foram realizados dois modelos experimentais em camundongos, modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl, que permitiram avaliar a atividade gastroprotetora dos extratos na dose de 250 mg/kg. Posteriormente, foram determinadas a área total de lesão (mm2) e a área relativa lesada (%). RESULTADOS Os resultados apresentaram atividade gastroprotetora significativa para todos os extratos estudados frente aos agentes agressores utilizados, etanol e indometacina. CONCLUSÃO Supõe-se que os frutos apresentam compostos bioativos, como as substancias antioxidantes, que atuam sobre os níveis de prostaglandinas, protegendo dos danos causados pelo etanol e indometacina. Os resultados encorajam futuros estudos para isolamento e identificação dos princípios ativos dos frutos.

Gastroprotective activity of the hydroethanolic extract and ethyl acetate fraction from Kalanchoe pinnata (Lam. ) Pers

ABSTRACT Peptic ulcers are an important pathology, and the search for safer and more effective treatment methods is of paramount importance. In this study, we assess the gastroprotective effects of the hydroethanolic extract (HE) and ethyl acetate fraction (EAF) from Kalanchoe pinnata leaves against an ethanol/HCl-induced ulcer model in rats. The HE reduced gastric lesions by approximately 47% (400 mg/kg). A significant inhibition of the gastric lesions by 50% was observed after pretreatment with the EAF (200 mg/kg). Quercetrin and quercetin 3-O-α-L-arabinopyranosyl-(1→2)-α-L-rhamnopyranoside were isolated and identified in the flavonoid fraction (EAF) by HPLC and NMR analyses because this fraction showed the highest gastroprotective effect. This fraction demonstrated high antioxidant activities (CE50=41.91 µg/mL) by DPPH in comparison with Trolox(r) and 11.33 mmol Trolox(r) equivalent by ORAC. In conclusion, the HE and FAE from K. pinnata displayed gastroprotective activity in rats, most likely due to the presence of flavonoids.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Medicina antienvelhecimento: notas sobre uma controvérsia sociotécnica / Anti-aging medicine: notes on a socio-technical controversy

Após algumas décadas de batalha, a geriatria e a gerontologia se tornaram as legítimas ciências do envelhecimento. Hoje surge uma contestação a tal condição. Em sua breve história, a medicina antienvelhecimento se afirmou como prática médica que questiona o modo de se endereçar o envelhecimento biológico. Com isso, toda a medicina é questionada. Aqui, exploramos especialmente como essa controvérsia se estrutura em torno dos fundamentos das ciências do envelhecimento. Há bases para esses questionamentos? Como eles foram tratados por aqueles que os receberam? Tendo em vista uma perspectiva sociotécnica, é interessante pensar que, para geriatras e gerontólogos, a necessária crítica à medicina antienvelhecimento também traz uma importante reflexão sobre o modo como as ciências do envelhecimento vêm tratando seu objeto.

After some decades of struggle, geriatrics and gerontology have become the legitimate sciences of aging. Today, their status is being questioned. In its short history, anti-aging medicine has taken root as a medical practice that questions how to address biological aging. In so doing, all medicine is questioned. Here, we explore in particular how this controversy is structured around the founding principles of the sciences of aging. Is there any basis for these questionings? How have they been treated by those who have received them? Taking a socio-technical viewpoint, it is worth considering that for geriatricians and gerontologists, the need to criticize anti-aging medicine also raises some important reflections about how the sciences of aging address their subject.

Efeito do agonista PPAR LYSO-7 sobre a instalação e cicatrização de úlceras gástricas induzidas em camundongos / Effect of PPAR agonist LYSO-7 on installation and healing of gastric ulcers induced in mice

A úlcera gástrica é uma doença crônica, de alta prevalência, e a eficácia dos tratamentos farmacológicos disponíveis é limitada pela alta incidência de efeitos adversos. Neste trabalho é mostrado o mecanismo de ação terapêutica e os efeitos toxicológicos da molécula indol-tiazolidínica LYSO-7 em diferentes modelos experimentais de úlcera gástrica. Camundongos Swiss machos foram tratados com veículo, LYSO-7 (5, 25 ou 50 mg/kg, v.o.) ou bezafibrato (25 ou 50 mg/kg, v.o.) 1 hora antes da administração oral de Et/HCl (60%/0,03 M) ou indometacina (100 mg/kg). Em outro conjunto de ensaios, animais foram pré-tratados com GW9962, um antagonista PPARγ (2 mg/kg, i.p.); anticorpo anti-granulócito (50 µL, i.p.), ou L-NAME (70 mg/kg, i.p) 1 hora antes dos tratamentos com veículo ou LYSO-7. Uma hora após administração da solução de Et/HCl, os neutrófilos foram quantificados no sangue e medula óssea, a rede microcirculatória gástrica foi estudada em in situ, utilizando a técnica de microscopia intravital; o tecido gástrico foi utilizado para quantificar a percentagem de área lesada, atividade da MPO, a expressão gênica e proteica de PPARγ, expressão proteica de iNOS e eNOS, e a atividade das enzimas catalase, SOD, GPx, GR e GST. Uma hora após a administração de indometacina, o tecido gástrico foi removido para avaliar a eficácia do tratamento e a secreção de mediadores inflamatórios. Ensaio de úlcera crônica, induzida por ácido acético, foi realizado em camundongos Balb/c WT ou ANXA1-/-, aplicando-se 20µL de ácido acético na camada subserosa do estômago e 24 horas após a indução, os animais foram tratados, uma vez ao dia, durante sete dias com LYSO-7 (50 mg/kg), bezafibrato (50 mg/kg) ou veículo. Foram realizados ensaios com macrófagos recrutados para o peritônio pela ação do tioglicolato de sódio (3%, i.p.) e com neutrófilos recrutados pela ação do glicogênio de ostra (1%, i.p.). Ensaios de toxicologia aguda, crônica e mutagenicidade também foram realizados. Os resultados obtidos mostram que o tratamento com LYSO-7 reduz a área lesada, o influxo de neutrófilos e a estase da rede microcirculatória provocada pela administração de Et/HCl. Os efeitos protetores foram revertidos em animais pré-tratados com GW9962, indicando a participação do PPARγ no efeito. O influxo de neutrófilos é determinante para a lesão, uma vez que a depleção destas células reduziu a ulceração gástrica, e indica que o bloqueio da mobilização de neutrófilos da medula óssea para o sangue e destes para o tecido lesado pela LYSO-7 pode ser um mecanismo de ação gastroprotetora desta molécula. A reversão da estase vascular na microcirculação, mas não o influxo de neutrófilos, é mediado pelo NO, pois o pré-tratamento com L-NAME aboliu os efeitos da LYSO-7 no restabelecimento do fluxo sanguíneo da microcirculação. Este efeito pode ser dependente da maior e menor expressão proteica de eNOS e iNOS, respectivamente. A LYSO-7 foi capaz de alterar favoravelmente a atividade das enzimas antioxidantes no tecido gástrico. Ainda, a LYSO-7 diminuiu a área lesada e reduziu a concentração de TNFα e aumentou a de IL-10 no tecido gástrico lesado pela indometacina. Na resolução do processo inflamatório, o tratamento com LYSO-7 diminuiu a percentagem de área lesada, aumentou a apoptose de neutrófilos e a eferocitose de neutrófilos por macrófagos peritoneais, inibiu a secreção de TNFα e aumentou a secreção de IL-10, TFG-1ß e VEGF para o sobrenadante de macrófagos em fagocitose. A resolução de lesão gástrica, bem como a indução da fagocitose pela LYSO-7 foi reduzida em animais ANXA1-/-. As investigações destes últimos dados mostraram a relação da ANXA1 e PPARγ, já que a expressão do receptor é reduzida em macrófagos obtidos de animais depletados de ANXA1. Os estudos toxicológicos mostraram que a LYSO-7 apresenta baixa toxicidade aguda e crônica in vivo, além de não ocasionar mutagenicidade em eritrócitos da medula óssea. Os dados obtidos mostram que a molécula LYSO-7 atua como agonista PPARγ na modulação da úlcera gástrica e modula a migração de neutrófilos e o fluxo sanguíneo na microcirculação. A transativação e transrepressão de eNOS e iNOS, respectivamente, o bloqueio da migração de neutrófilos para a lesão e a inibição da atividade de enzimas oxidativa, ativação de enzimas antioxidantes no epitélio gástrico e a inibição da secreção de mediadores inflamatórios parecem ser os mecanismos de ação da LYSO-7 na citoproteção gástrica. Adicionalmente, a LYSO-7 atua na resolução do processo inflamatório promovendo downregulation na secreção de mediadores inflamatórios, aumento na apoptose de neutrófilos e eferocitose de neutrófilos apoptóticos

Gastric ulcer is a chronic disease that presents high prevalence, and effectiveness of pharmacological treatments available is limited by several adverse effects. In this study is shown the mechanism of action and toxicological effects of the molecule indole-thiazolidine LYSO-7 in different models of gastric ulcer. Male Swiss mice were treated with vehicle LYSO-7 (5, 25, or 50 mg/kg, p.o.) or bezafibrate (25 or 50 mg/kg, p.o.) 1 hour before the oral administration of Et/HCl (60%/0.03 M) or indomethacin (100 mg/kg). In another set of assays, animals were pre-treated with GW9962, a PPARγ antagonist (2 mg/kg, i.p.), anti-granulocyte antibody (50 µL, i.p.) or L-NAME (70 mg/kg, i.p.) 1 hour before the treatment with vehicle or LYSO-7. One hour after administration of the Et/HCl solution, neutrophils were quantified in the blood and bone marrow, the gastric microcirculatory network was studied in situ by intravital microscopy, in the gastric tissue were quantified the percentage of injured area, MPO activity, PPARγ gene and protein expression, iNOS and eNOS protein expression, and catalase, SOD, GPx, GR and GST activity. One hour after indomethacin administration, gastric tissue was removed to verify the efficacy of LYSO-7 on inflammatory mediator secretion. Chronic ulcer assay induced by acetic acid was carried out in Balb/c WT or ANXA1-/-, applying 20µL of acetic acid in the subserosal layer of the stomach and 24 hours after induction, animals were treated during seven days, once a day, with LYSO-7 (50 mg/kg), bezafibrate (50 mg/kg) or vehicle. Assays were performed with macrophages recruited to the peritoneum by sodium thioglycollate (3%, i.p.) and neutrophils by oyster glycogen (1%, i.p.). Acute and chronic toxicological and mutagenicity assays were also conducted. The results obtained show that LYSO-7 treatment decrease the injured area, neutrophil influx and microcirculatory stasis evoked by Et/HCl administration. Protective effects were reversed in animals pretreated with GW9962, indicating the involvement of PPARγ. Neutrophil influx is a determinant of the gastric lesion, once the depletion of these cells decreased the gastric damage, indicating that in the neutrophil mobilization blockade from the bone marrow to blood and to injured tissue may be a gastroprotective mechanism of LYSO-7. The vascular stasis reversion in the microcirculation is mediated by NO, but not the neutrophil influx, since the pretreatment with L-NAME abolished the effects of LYSO-7 on blood flow. This effect was dependent on increase and decrease of eNOS and iNOS protein expression, respectively. LYSO-7 positively altered the activity of antioxidant enzymes in the gastric tissue. Furthermore, LYSO-7 reduced the injured area and the concentration of TNFα and increased IL-10 in the gastric tissue in the indomethacin-induced ulcer model. In the resolution of inflammation, LYSO-7 treatment decreased the percentage of the injured area, increased the neutrophils apoptosis and the efferocytosis of apoptotic neutrophils by peritoneal macrophages, inhibited the TNFα release and increased the secretion of IL-10, IL-1ß and VEGF in the supernatant of phagocytosis assay. The resolution of gastric lesions, as well as, the induction of phagocytosis by LYSO-7 was reduced in animals ANXA1-/-. This data shown the relation of PPARγ and ANXA1, as PPARγ expression is reduced in macrophages obtained from ANXA1-/- animals. Toxicological studies showed that LYSO-7 has low acute and chronic toxicity in vivo, and did not cause mutagenicity in bone marrow erythrocytes. The data obtained show that LYSO-7 acts as PPARγ in the modulation of gastric ulcer and modulate neutrophil migration and blood flow in the microcirculation. The transactivation and transrepression of eNOS and iNOS, respectively, blocking the neutrophil influx into the injury, antioxidant enzymes activation in the gastric epithelium and inhibition of inflammatory mediators release seem to be the mechanisms action of LYSO-7 in gastric cytoprotection. Additionally, LYSO-7 operates in the resolution of inflammation promoting downregulation in the secretion of inflammatory mediators and increases the neutrophil apoptosis and efferocytosis of apoptotic neutrophils

Vasodilators versus lansoprazole in prevention of ethanol induced gastric ulcer

Peptic ulcer is a condition result from imbalance between the erosive effect of acid and pepsin and mucosal defense mechanism in the stomach and may be correlated with vasodilators. Forty two healthy albino male rats weighing [180-200] gram were involved in this study. The animals were allocated to six groups. Each group was given one of the following drugs: Lansoprazole, amlodipine, amiodarone, carvedilol and distilled water as control. After 5 days of treatment with these agents, ethanol 95% was administered orally after one hour of the last dose of these agents. Animal were sacrificed after one hour later. The main parameters used in this study were ulcer preventive index, free radicals, changing of serum electrolytes. Ethanol in high concentrations was found to be highly ulcerogenic agent with ratio of 100% when administered orally in rat The preventive index [PI] of these drugs equal 86.95,96.99and 83.63 for amlodipine, amiodarone andcarvedilol respectively in comparing with lansoprazole 99.09. All the tested drugs and lansoprazole produced highly significant change in free radicals of the gastric tissue decreasing MDA levels andincreasing GSH levels. Some of serum electrolytes were significantly changed by the tested drugs. Amlodipine, amiodarone and carvedilol proved to have gastro-protective activity against ethanol induced gastric ulcer and the possibility to be used for patients with peptic ulcer or cardiovascular problems with peptic ulcer

Effect of Gongronema latifolium ethanol leaf extract on gastric acid secretion and cytoprotection in streptozotocin-induced diabetic rats / Efecto del extracto de etanol de las hojas de Gongronema latifolium sobre la secreción del ácido gástrico y la citoprotección en ratas con diabetes inducida por estreptozotocina

OBJECTIVES: Gongronema latifolium leaves have been used in folklore medicine to manage diabetes mellitus and alleviate dyspepsia. This study aimed to provide a pharmacological basis to the medicinal use of Gongronema latifolium as an antidiabetic and antiulcerogenic agent in diabetes mellitus. METHODS: Ethanol extract from the leaf (200 mg/kg bodyweight) of Gongronema latifolium was administered to both streptozotocin-induced diabetic and control groups orally for 14 days. Gastric acid secretion was measured and ulcer was induced using ethanol and fourhour pyloric ligation. RESULTS: The mean bodyweight was significantly lower (p < 0.01), while the mean weight of the stomach, liver and small intestine to bodyweight ratio was increased significantly (p < 0.05) in the two diabetic groups compared to control. Extract significantly (p < 0.01) reduced the blood glucose level similar to the nondiabetic control. Basal and stimulated acid secretion in diabetic control rats was significantly (p < 0.01) decreased when compared to control. Extract administration increased the stimulated gastric acid secretion to a level significantly (p < 0.05) higher than control while reduction in gastric secretion by ranitidine was similar compared with control. Gongronema latifolium treatment significantly (p < 0.05) reduced ulcer scores in both ulcer models and increased mucus weight in the diabetic group. CONCLUSION: These results suggest that Gongronema latifolium antiulcerative activity is due to its prevention of chemicalinduced stomach injury.

OBJETIVOS: Las hojas de la gongronema latifolium han sido usadas en la medicina tradicional para tratar la diabetes mellitus y aliviar la dispepsia. Este estudio estuvo dirigido a proporcionar una base farmacológica al uso medicinal de la gongronema latifolium como agente antidiabético y antiulcerogénico en la diabetes mellitus. MÉTODOS: El extracto de etanol de la hoja (200 mg/kg peso corporal) de la Gongronema latifolium se administró oralmente durante 14 días a grupos con diabetes inducida por estreptozotocina, y grupos de control. La secreción ácida gástrica fue moderada y la úlcera fue inducida usando etanol, y ligazón pilórica de cuatro horas. RESULTADOS: El peso corporal promedio fue significativamente más bajo (p < 0.01), mientras que el peso promedio del estómago, el hígado y el intestino delgado con respecto a la proporción del peso corporal aumentó significativamente (p < 0.05) en los dos grupos diabéticos comparados con los controles. El extracto redujo significativamente (p < 0.01) el nivel de glucosa de la sangre, de manera similar al control no diabético. La secreción ácida basal y estimulada en las ratas diabéticas control disminuyó significativamente (p < 0.01) en comparación con el control. La administración del extracto aumentó la secreción ácida gástrica estimulada a un nivel significativamente (p < 0.05) superior al control, en tanto que la reducción de secreción gástrica mediante ranitidina fue similar comparada con el control. El tratamiento con Gongronema latifolium redujo significativamente (p < 0.05) las puntuaciones de las úlceras, tanto en los modelos de la úlcera como en el peso de mucosidad aumentado en el grupo diabético. CONCLUSIÓN: Estos resultados sugieren que la actividad antiulcerosa de la Gongronema latifolium se debe a que previene las lesiones de estómago inducidas por medios químicos.

Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study / Úlcera perianastomótica após derivação gástrica em Y-de-Roux mesmo em uso de inibidor de bomba de prótons: estudo prospectivo multicêntrico

CONTEXT: Causal factors of gastrojejunal ulcers after Roux-en-Y gastric bypass include peptic acid secretion from the gastric pouch. Esomeprazole is a potent inhibitor of acid secretion. OBJECTIVE: To assess the occurrence of dyspepsia and gastrojejunal ulcers within the first 2 months after Roux-en-Y gastric bypass during the use of esomeprazole. METHODS: One hundred eighteen morbid obese subjects were submitted to Roux-en-Y gastric bypass. Preoperative upper gastrointestinal tract endoscopy was negative for H. pylori. All subjects received esomeprazole for 60 days after surgery. RESULTS: Two weeks after surgery only 13 mild symptoms were reported. After 2 months, 17 also moderate complaints were registered. Endoscopy around the 60th day showed esophagitis in 10 (8.5 percent), hiatal hernia in 2 (1.7 percent), foreign body in the anastomotic line in 12 (10.2 percent) and gastrojejunal ulcers was observed in 9 (7.6 percent) subjects, 2 of which had a suture material or metallic staple granuloma in the gastrojejunostomy. Ten subjects took nonsteroidal anti-inflammatory drugs at least once during study, but none of them developed ulcer. None of the subjects with ulcer had dyspeptic symptoms. CONCLUSION: The incidence of ulcer in the gastrojejunal anastomosis within the first 2 months following Rouxen-Y gastric bypass under proton pump inhibitors is considerable. It was not related to the use of non-steroidal anti-inflammatory drugs, highlighting the possibility of ischemia and foreign body as causal factors. The ulcers were asymptomatic, and all post-surgical dyspeptic symptoms were moderate in severity.

CONTEXTO: Sintomas dispépticos são comuns após derivação gástrica em Y-de-Roux. Podem decorrer de úlceras de boca anastomótica, cujos possíveis fatores causais incluem a secreção cloridropéptica da bolsa gástrica, isquemia, efeito de corpo estranho dos materiais de sutura e uso de antiinflamatórios não-esteróides. O esomeprazol é um redutor potente da secreção ácida, capaz de diminuir sintomas pépticos e evitar lesões mucosas, mesmo em pacientes usuários de antiinflamatórios não-esteróides. OBJETIVOS: Estudo prospectivo não-randomizado procura avaliar a ocorrência de dispepsia e úlceras perianastomóticas nos 2 primeiros meses após derivação gástrica em Y-de-Roux. MÉTODOS: Cento e dezoito obesos mórbidos foram operados em quatro centros de cirurgia bariátrica pela técnica de derivação gástrica em Y-de-Roux por laparotomia ou laparoscopia. À endoscopia digestiva alta, H. pylori estava ausente. Todos os operados tomaram 20 mg de esomeprazol por dia do 3º ao 60º pós-operatório. RESULTADOS: Entre o 10º e o 15º dia, nenhum paciente referiu epigastralgia ou pirose, um referiu vômitos moderados, quatro dor abdominal e oito náuseas. Entre o 55º e o 65º dia, três referiram epigastralgia leve, seis vômitos, um dor abdominal, dois náuseas e seis pirose. O exame endoscópico neste período revelou esofagite em 10 pacientes (8,5 por cento), hérnia hiatal em 2 (1,7 por cento) e corpo estranho nas linhas de sutura em 12 (10,2 por cento). Em nove pacientes (7,6 por cento) encontrou-se úlcera de boca anastomótica ou adjacente a ela, em dois incluindo granuloma de fio de sutura ou de grampo metálico. Dez pacientes utilizaram alguma vez antiinflamatórios não-esteróides nos 2 meses de estudo, nenhum deles apresentando úlcera. CONCLUSÕES: A ocorrência de úlcera de boca anastomótica 2 meses após derivação gástrica em Y-de-Roux, é considerável, mesmo em uso de esomeprazol. Não houve relação com ingestão de antiinflamatórios não-esteróides, o que realça as possibilidades...

Gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves against acute gastric lesion models in rodents

Parkia platycephala Benth. (Leguminosae - Mimosoideae), popularly known as "visgueira", fava bean tree or "fava-de-bolota", is widely found in the Northern and Northeastern regions of Brazil. Its pods are used as cattle food supplement in the drought period. Compounds with a gastroprotective activity were obtained from the genus Parkia. Therefore, this study aimed at investigating the gastroprotective effect of the ethanolic extract of Parkia platycephala Benth. leaves (Pp-EtOH), as well as evaluating its possible mechanisms of action in experimental ulcer induction models. Lesions were induced by absolute ethanol, ethanol-HCl, ischemia-reperfusion and indomethacin in rodents. Pp-EtOH showed a protective effect in the lesion models (66, 48 and 52 percent, respectively), but it was not able to protect gastric mucosa against indomethacin-induced lesions. Results show a possible participation of the NO-synthase pathway in the gastroprotection and an antioxidant activity, by the increase of the catalase activity. The participation of prostaglandins and potassium channels sensitive to ATP in the gastroprotective effect of Pp-EtOH seems less likely to occur. More comprehensive studies, therefore, should be carried out to elucidate the antiulcerative effects of this promising natural product against this gastrointestinal disorder.

Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents

This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53 percent), ethanol/HCl (75 percent), ibuprofen (52 percent) and ischemia/reperfusion (43 percent). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.

Gastroprotective effects of aqueous extract of Chamomilla recutita against ethanol-induced gastric ulcers

To investigate the gastroprotective effects of an orally administered aqueous extract of Chamomilla recutitia [ACE] against ethanol-induced gastric ulcers in male Wistar rats. This study was performed during January and February 2009, in the Research Labs in the Department of Physiology at the Medical School, King Khalid University, Abha, Kingdom of Saudi Arabia. Sixty white albino rats were divided into 5 groups. Group 1 [control group] was treated with deionized water for 28 days; animals in group 2 to group 5 received zero, 0.5, 1, or 2 gm/kg ACE fro 27 days. Stomach ulcerations were induced by orally administering a single dose of 70% ethanol on day 28. Lesions in the gastric mucosa were examined macroscopically to calculate the ulcer index [UI] and estimated glutathione [GSH] for each animal. Compared to non-ACE treated rats, the UI decreased significantly in a dose-dependent manner in treated animals. Furthermore, GSH levels fell significantly after ethanol treatment; this decrease was prevented by ACE treatment. However, daily treatment of rats with the maximum ACE dose actually led to an increase in GSH levels. Histological examination revealed that ACE treatment alleviated, or completely resolved ethanol-induced degenerative alterations, including disorganization of cell nuclei and gland morphology with erosion in the gastric mucosa and interrupted muscularis mucosa. This study provides evidence for the regulation of ACE-mediated gastroprotection against ethanol-induced ulceration by GSH

[ effect of omeprazol and ranitidine on gastric acidity in ICU patients]

ICU patients especially those under mechanical ventilation or with a history of coagulation disorders are at the risk of stress ulcer development and related GI bleeding. Typically H2 blockers administration showed prophylactic role to control gastric acidity. Preliminary studies have shown that administration of intravenous omeperazol is effective. The object of this study was to compare the effect of oral rout administration of omerprazol with intravenous ranitidine on gastric pH. In this experimental study 40 ICU patients under mechanical ventilation allocated into same conditions and matched ranitidine and omeprazol groups [20 subjects in each group]. First group received 50 mg intravenous ranitidine twice per day and the second group received 40 mg oral omeperazol once a day. The gastric acidity was monitored using Chroning method. Gastric pH was determined before administration and three times per day after drugs administration then followed for three consequent days. Data was analyzed using T-test and SPSS software. The mean gastric pH in the Ranitidine group was 2.07 +/- 0.79 before and 2.80 +/- 0.85 after drug administration. In the Omperazol group gastric pH was 2.01 +/- 1.52 before and 3.90 +/- 1.52 after drug administration. The oral Omeperazol administration was significantly effective than intravenous Ranitidine administration [p<0.005]. Our data suggest that in critically ill patients oral rout administration of Omeparazol is more effective than intravenous H2 blocker [Ranitidine] to decrease gastric acidity and may prevent from stress ulcer

Caracterìsticas de fìstulas enterocutàneas en pacientes postoperados del tubo digestivo concurrentes al servicio de cirugìa general del HC-IPS. Periodo de marzo-mayo del 2009 / Characteristics of postoperative enterocutaneous fistulas in patients with concurrent gastrointestinal tract of general surgery at the HC-IPS marzo-may period of 2009

Se denomina fìstula a un trayecto cuyas paredes estàn formadas,generalmente,por tejido de granulaciòn y que comunica dos superficies revestidas de epitelio.

Antiulcer and anticonvulsant activity of Croton zambesicus

The ethanolic root extract of Croton zambesicus was investigated for its potential to protect gastric mucosa against ulcers induced by indomethacin, ethanol and reserpine. The anticonvulsant activity of the root extract against pentylene tetrazol[PTZ]- and picrotoxin-induced convulsion in mice was also studied. The extract [27-81mg/kg] produced a significant [P<0.005-0.001] dose-dependent effects against the ulcerogenic effect of differents agents used; indomethacin, ethanol and reserpine. The effect of the extract was lower than that of the standard drug, cimetidine [100mg/kg] in the indomethacin and reserpine-induced ulcer models and higher than that of propranolol [40mg/kg] in ethanol- induced ulcer model. The extract [27-81mg/kg] could not protect mice from convulsion in both PTZ - and picrotoxin- induced convulsion. The root extract significantly [P<0.01-0.001] delayed the onset and latency of convulsion caused by PTZ and picrotoxin. The root extract possesses antiulcer and anticonvulsant properties

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats / Efecto protectivo del extracto de la hoja de Carica papaya L contra el daño gástrico agudo inducido por alcohol y el estrés oxidativo en ratas

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Los efectos de; extracto acuoso de la hoja de Carica papaya (CPL) en el daño gástrico agudo inducido por alcohol y el nivel de estrés oxidativo inmediato en la sangre, fueron estudiados en ratas. Los resultados mostraron que el índice de úlcera gástrica se reducía significativamente en ratas pre-tratadas con extracto de CPL, en comparación con los controles tratados con alcohol. Los estudios in vitro mediante el ensayo con 2,2-difenil-1-picrihidrazilo) mostraron la fuerte naturaleza antioxidante de extracto de CPL. El análisis bioquímico indicó que el daño agudo inducido por alcohol se refleja en las alteraciones de los índices oxidativos de la sangre y el extracto de CPL ofreció cierta protección con la reducción del nivel de peroxidación lipídica del plasma y el aumento de la actividad de la glutatión peroxidasa de los eritrocitos. La hoja de la Carica papaya puede servir potencialmente como un buen agente terapéutico para la protección contra la úlcera gástrica y el estrés oxidativo.

Effects of the oil and mucilage from flaxseed [linum usitatissimum] on gastric lesions induced by ethanol in rats

The anti-ulcer activity of the oil and mucilage obtained from flaxseed [Linum usitatissimum] was evaluated in a rat model of ethanoHnduced gastric ulcer. Our results show that pretreatment of rats with flaxseed oil and flaxseed mucilage significantly reduced the number and length of gastric ulcers induced by ethanol. Flaxseed oil was more effective than flaxseed mucilage in reducing the number of ulcers. The reduction in ulcer severity [cumulative length in mm] provided by an oral dose of flaxseed oil [5 ml/kg] was more prominent than that obtained by ranitidine [50 mg/kg]. This study indicates that both flaxseed oil and flaxseed mucilage can provide a cytoprotective effect against ethanol-induced gastric ulcers in rats