Gastroprotective potential and mechanisms of action of Hedera nepalensis

Abstract Hedera nepalensis (H. nepalensis) , belonging to the family Araliaceae, is a medicinal plant traditionally used to treat stomach problems. The current study investigated the gastroprotective potential and the mechanism of action of H. nepalensis in diclofenac-and ethanol-induced ulcer models. Anti-oxidant and lipid peroxidation inhibitory prospects of H. nepalensis were checked out by free radical scavenging assay and UV spectrophotometer respectively. Effect of H. nepalensis on the pH, gastric total acidity of gastric juice and protective effects of H. nepalensis against ulcer models have been examined. Histopathological studies have been carried out. The aqueous methanol extract of H. nepalensis (100 µg/mL) showed anti-oxidant (83.55%) and lipid peroxidation inhibitory (70.88%) potential at 1000 µg/mL; the extract had no buffer potential. The extract (400 mg/kg) significantly (81.12% and 63.46%) showed gastroprotective effect in diclofenac and ethanol-induced rat ulcer models respectively. Histopathological studies confirmed the biochemical findings. FTIR analysis showed the presence of carboxylic acid, alkanes, conjugated alkanes, aldehydes and alkyl-aryl ethers. Gallic acid, M-coumaric acid and quercetin were found by HPLC analysis. H. nepalensis exhibited significant protection against diclofenac and ethanol induced gastric damage by anti-oxidant and lipid peroxidation suppression effects suggesting potential broad utility in treatment of diseases characterized with gastric damage.

Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation

Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer

Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali

Diseases of the digestive system of agoutis (Dasyprocta leporina) raised in captivity in the Brazilian semiarid region / Doenças do sistema digestivo de cutias (Dasyprocta leporina) criadas em cativeiro na região semiárida brasileira

The objective of this study was to describe the clinical and pathological aspects of diseases of the digestive system in agoutis (Dasyprocta leporina Linnaeus, 1758) diagnosed by the "Laboratório de Patologia Veterinária" (Veterinary Pathology Laboratory) of the "Universidade Federal Rural do Semi-Árido" (UFERSA), from January 2018 to February 2020. During the study period, necropsy and a survey of the clinical history of 27 agoutis were performed, 25.93% (7/27) of which were diagnosed with digestive system diseases. The percentages of digestive tract diseases among the diagnosed were: acute carbohydrate overload (11.12%), gastric ulcer (7.41%), gastric volvulus (3.70%), and intestinal volvulus (3.70%). Studies on the occurrence rate of these diseases, as well as the description of their clinical and anatomopathological aspects, may serve as a basis for guiding the appropriate management in the breeding of these animals.(AU)

O objetivo deste estudo foi descrever os aspectos clínicos e patológicos das doenças do aparelho digestivo em cutias (Dasyprocta leporina Linnaeus, 1758) diagnosticadas pelo Laboratório de Patologia Veterinária da Universidade Federal Rural do Semiárido (UFERSA), de janeiro 2018 a fevereiro de 2020. Durante o período do estudo, foram realizadas necropsias e levantamento da história clínica de 27 cutias, sendo 25,93% (7/27) diagnosticadas com doenças do aparelho digestivo. Os percentuais de doenças do aparelho digestivo foram: sobrecarga aguda de carboidratos (11,12%), úlcera gástrica (7,41%), vólvulo gástrico (3,70%) e vólvulo intestinal (3,70%). Estudos sobre a taxa de ocorrência dessas doenças, bem como a descrição de seus aspectos clínicos e anatomopatológicos, podem servir de base para orientar o manejo adequado na criação dessa espécie.(AU)

Diseases of the digestive system of agoutis (Dasyprocta leporina) raised in captivity in the Brazilian semiarid region / Doenças do sistema digestivo de cutias (Dasyprocta leporina) criadas em cativeiro na região semiárida brasileira

The objective of this study was to describe the clinical and pathological aspects of diseases of the digestive system in agoutis (Dasyprocta leporina Linnaeus, 1758) diagnosed by the "Laboratório de Patologia Veterinária" (Veterinary Pathology Laboratory) of the "Universidade Federal Rural do Semi-Árido" (UFERSA), from January 2018 to February 2020. During the study period, necropsy and a survey of the clinical history of 27 agoutis were performed, 25.93% (7/27) of which were diagnosed with digestive system diseases. The percentages of digestive tract diseases among the diagnosed were: acute carbohydrate overload (11.12%), gastric ulcer (7.41%), gastric volvulus (3.70%), and intestinal volvulus (3.70%). Studies on the occurrence rate of these diseases, as well as the description of their clinical and anatomopathological aspects, may serve as a basis for guiding the appropriate management in the breeding of these animals.

O objetivo deste estudo foi descrever os aspectos clínicos e patológicos das doenças do aparelho digestivo em cutias (Dasyprocta leporina Linnaeus, 1758) diagnosticadas pelo Laboratório de Patologia Veterinária da Universidade Federal Rural do Semiárido (UFERSA), de janeiro 2018 a fevereiro de 2020. Durante o período do estudo, foram realizadas necropsias e levantamento da história clínica de 27 cutias, sendo 25,93% (7/27) diagnosticadas com doenças do aparelho digestivo. Os percentuais de doenças do aparelho digestivo foram: sobrecarga aguda de carboidratos (11,12%), úlcera gástrica (7,41%), vólvulo gástrico (3,70%) e vólvulo intestinal (3,70%). Estudos sobre a taxa de ocorrência dessas doenças, bem como a descrição de seus aspectos clínicos e anatomopatológicos, podem servir de base para orientar o manejo adequado na criação dessa espécie.

Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol extract and its isolated component isoorientin on indomethacin induced gastric ulcers in rats

Abstract Purpose: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. Methods: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. Results: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). Conclusions: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.

Farmacologia e fitoquímica de extratos e formulações de Jacaranda decurrens Cham., Jacaranda caroba (Vell.) DC. e Piper umbellatum L / Pharmacology and phytochemistry of extracts and formulations from Jacaranda decurrens Cham., Jacaranda caroba (Vell.) DC. and Piper umbellatum L

Jacaranda decurrens Cham., Jacaranda caroba (Vell.) DC. e Piper umbellatum L. são plantas nativas do Brasil, presentes no estado de São Paulo, com relatos de uso popular para atividade antiúlcera. Este trabalho teve como objetivo avaliar a atividade antiúlcera de J. caroba, J. decurrens e formulações de nanocápsulas contendo P. umbellatum. Também pretendeu-se caracterizar a fitoquímica de tais formulações e extratos. Adicionalmente, foi avaliada a toxicidade aguda e subaguda de J. caroba. Os extratos de Jacaranda apresentaram compostos fenólicos em seus perfis cromatográficos obtidos por CCD e CLAE, característicos para cada espécie. Os diferentes extratos de J. caroba variaram sua composição química conforme a procedência e idade da planta. As espécies J. decurrens e J. caroba de três diferentes regiões não apresentaram ação antiúlcera aguda em ratos em modelo de indução por etanol acidificado, embora o extrato e as frações de J. caroba apresentaram potencial atividade anti Helicobacter pylori, com CIM variando entre 125 e 1.000 µg/mL. O extrato de J. caroba não promoveu sintomas de toxicidade aguda e subaguda em ratos. A DL50 observada foi maior que 5.000 mg/kg. Não foram relatadas alterações significativas na aparência macroscópica e peso dos órgãos, porém houve indicação de atividade mutagênica em teste de Ames na linhagem TA98 de S. typhimurium, o qual apresentou uma tendência dose-resposta para concentrações entre 7,5 e 15,0 mg/placa após ativação metabólica (S9). A formulação de nanocápsulas de poli-ε- caprolactona com extrato de P. umbellatum apresentou partículas com diâmetro médio de 181,6 ± 0,9 nm e potencial zeta de -31 ± 4 mV. Através de análise por CLAE observou-se maior eficiência de encapsulamento para a porção mais apolar da fração, enquanto que os compostos mais polares ficaram dispersos no meio. As nanocápsulas poliméricas apresentaram atividade gastroprotetora mesmo sem a adição de ativos e tiveram sua atividade aumentada pela fração clorofórmica de P. umbellatum

Jacaranda decurrens Cham., Jacaranda caroba (Vell.) DC. and Piper umbellatum L. are native plants in Brazil, present in the state of São Paulo, with popular usage reports for anti-ulcer activity. This study aimed to evaluate the anti-ulcer activity of J. caroba, J. decurrens and nanocapsules formulations containing P. umbellatum. Also, we intended to characterize the phytochemistry of such formulations and extracts. Additionally, we evaluated the acute and subacute toxicity of J. caroba. Extracts from Jacaranda presented phenolic compounds in their chromatographic profiles obtained by TLC and HPLC, with variations between species. Samples of J. caroba extracts showed different chemical composition according to the origin and age of the plant. The species J. decurrens and J. caroba from three different regions showed no acute anti-ulcer action when tested in rats by acidified ethanol induction model. However, extract and fractions from J. caroba showed potential anti Helicobacter pylori activity, with MIC ranging from 125 and 1,000 ug/mL. J. caroba extract did not cause symptoms of acute and subacute toxicity in rats. The DL50 was determined above 5,000 mg/kg. Also, there were no significant changes to the macroscopic appearance of organs or changes in their weights. Meanwhile, an indication of mutagenic activity was observed in the Ames test. The TA98 strain of S. typhimurium, showed a tendency of dose-response for concentrations between 7.5 and 15.0 mg/plate after metabolic activation (S9). The nanocapsules formulation of poly-ε-caprolactone containing P. umbellatum extract had an average particle diameter of 181.6 ± 0.9 nm and zeta potential of -31 ± 4 mV. HPLC analysis showed better entrapping efficiency for the more apolar portion of the fraction, while the more polar compounds were dispersed in the medium. The polymeric nanocapsules showed gastroprotective activity even without the addition of active molecules and had their activity increased by chloroform fraction of P. umbellatum

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

Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (cabbage) on Wistar rat gastric ulceration / Avaliação da atividade antiúlcera do extrato aquoso de Brassica oleracea var. capitata (repolho) em úlceras gástricas de ratos Wistar

CONTEXT: The cabbage (Brassica oleraceae var. capitata) is an herbaceous and leafy plant which belongs to the Brassicaceae family, native to coastal southern and Western Europe. Used in cooking for its nutritional value also has known anti-inflammatory activity. OBJECTIVE We studied the antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (AEB) in order to validate ethnobotanical claims regarding the plant use in the gastric disorders. METHOD: Acute gastric ulcers were induced in rats by the oral administration of acetylsalicylic acid. The gastroprotective potential of the AEB (0.250, 0.500 and 1.000 mg.kg-1/body weight) was compared with omeprazole (20 mg.kg-1/body weight). RESULTS: The stomach analysis indicated that treatment with AEB inhibited the gastric damage. The gastroprotective activity as evidenced by its significant inhibition in the formation of ulcers induced by chemical agent with a maximum of 99.44 percent curation (250 mg.kg-1 body weight) in acetylsalicylic acid-induced ulcers. CONCLUSIONS: The AEB demonstrated good antiulcerogenic activities which justify the inclusion of this plant in the management of gastric disorders. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

CONTEXTO: O repolho (Brassica oleracea var. capitata) é uma planta de folhas herbáceas pertencente à família Brassicaceae, nativa na costa sul e oeste da Europa. Usado na culinária por seu valor nutritivo, possui conhecida atividade anti-inflamatória. OBJETIVO: Avaliar a atividade antiulcerogênica do extrato aquoso de Brassica oleracea var. capitata (AEB), a fim de validar os conhecimentos etnobotânico do uso da espécie em distúrbios gástricos. MÉTODO: Úlceras gástricas foram induzidas em ratos pela administração oral de ácido acetilsalicílico. O potencial gastroprotetor de AEB (0,250, 0,500 e 1,000 mg.kg-1/peso) foram comparados com omeprazol (20 mg.kg-1/peso). RESULTADOS: As análises dos estômagos indicaram que o tratamento com AEB inibiu a progressão da lesão gástrica. A atividade gastroprotetora foi evidenciada por sua significativa inibição da progressão da úlcera induzida por agentes químicos, com o máximo de 99,44 por cento eficácia (250 mg.kg-1/peso) frente a úlceras gástricas induzidas por ácido acetilsalicílico. CONCLUSÕES: O AEB demonstrou atividade cicatrizante de úlceras gástricas, o que justifica a inclusão da espécie em tratamentos de distúrbios gástricos. Estudos futuros estão em andamento para determinar quais os mecanismos antiulcerogêncios estão envolvidos com a gastroproteção.

Expression of TERT in precancerous gastric lesions compared to gastric cancer

The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46 percent of IM, 50 percent of GU, and 79 percent of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38 percent of IM, 39 percent of GU, and 55 percent of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.

Possible protective effect of gum arabic on experimentally induced gastric ulcer in adult male albino rats: a histological and immunohistochemical study

Peptic ulcer is a serious disease with a high incidence of occurrence in our community. Gum arabic [GA] is an edible, dried, gummy exudate from the stems and branches of Acacia senegal. It has been claimed to act as an antioxidant. The aim of this study was to evaluate the protective effect of GA on stress-induced peptic ulcer in rats. In this study, 30 adult male rats were divided equally into three groups: the control group [group I], the stress ulcer group [group II], and the GA group [group III]; the GA group received GA 7.5 g/kg/day through an orogastric tube for 10 days. After 10 days, the rats were fasted for 24 h. Cold immobilization stress was induced in groups II and III. The animals of all groups were then anesthetized with diethyl ether, and their stomachs were isolated immediately, opened from the greater curvature, and washed with saline. Ulcer severity, ulcer score, and ulcer index were determined. Stomach specimens were fixed in 10% neutral-buffered formalin for histological, hematoxylin and eosin, histochemical, Periodic Acid Schiff's [PAS], and Masson's trichrome stainings and for immunohistochemical detection of proliferating cell nuclear antigen [PCNA]. Pretreatment with GA significantly decreased the gastric lesions. Both ulcer severity and score were significantly decreased [32.8% and 39.58%, respectively] compared with the stress-untreated group. Ulcer index was significantly decreased [49%] compared with the stress group [P< 0.05]. The stress group showed atrophic gastric mucosa with loss of glandular tissue [hematoxylin and eosin], positive PAS reaction in the mucus neck cells, many collagen fibers between the atrophic glands, and moderate PCNA reaction in the glandular cells. In the GA group, there was nearly normal gastric mucosa with a small area of atrophied surface epithelium, PAS-positive reaction in surface and neck mucus cells, some collagen fibers between the near normal gastric glands, and mild PCNA reaction in the gland cells. It can be concluded that GA exerts a protective effect against stress-induced gastric mucosal lesions in rats

possible role for gastroprotectives on aspirin-induced gastric ulcer in rats

Gastric ulcer is a discontinuity in the gastric mucosa that occurs due to imbalance between gastric mucosal protective factors and aggressive factors. The Aim of the present work was to test and compare the protective effects of an antisecretory H2 receptor blocker; ranitidine and other recently suggested gastroprotective drugs: L-arginine; a precursor of NO, zinc sulfate; an anti-inflammatory antioxidant agent and pioglitazone; a PPAR-gamma agonist, on a rat model of aspirin induced gastric ulcer. Acute gastric lesion was induced in rats by a single oral dose of aspirin 300mg/ kg body weight. L-arginine 200mg / kg b. wt, zinc sulfate 80 mg/ kg b. wt, and pioglitazone 10 mg / kg b. wt. were given alone and in combination with ranitidine 50 mg / kg b. wt for 3 days before induction of gastric lesion. Aspirin induced a significant increase in gastric mucosal lesion score and free and total gastric hydrochloric acid with a significant decrease in gastric nitric oxide and mucin levels as compared to normal group. A significant increase in gastric malondialdhyde and decrease in reduced glutathione as compared to normal group. L-arginine, zinc sulfate, and pioglitazone produced improvement of most of the measured parameters as compared to non-treated group. Combination of L-arginine and ranitidine was superior in prophylaxis against aspirin-induced gastric ulcer when compared to the effects of each drug used individually, and the other studied combinations. The role of HCl and NO seems more important in the pathogenesis of aspirin induced gastric ulcer, as evidenced by the better protective effects of combination of ranitidine and L-arginine in comparison to the ranitidine with either zinc sulfate or pioglitazone

The cytoprotective effect of a nitric oxide donor drug on gastric mucous membrane of rats treated with ketoprofen, a non-steroidal anti-inflammatory drug / Efeito citoprotetor de uma droga doadora de óxido nítrico na membrana da mucosa gástrica de ratos tratados com o antiinflamatório não-esteróide - o cetoprofeno

BACKGROUND: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent. AIM: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment. METHODS: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration. RESULTS: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared...

RACIONAL: Drogas antiinflamatórias não-esteróides são consideradas, atualmente, importante grupo de medicamentos, com ampla variedade de uso terapêutico, em diferentes áreas da medicina moderna. Apesar de seus efeitos benéficos para o paciente, apresentam grande incidência de efeitos colaterais, principalmente no trato gastrointestinal. Os mecanismos fisiopatológicos de lesões induzidas por essas drogas e os mecanismos de defesa da mucosa gástrica tornaram-se uma importante linha de pesquisa médica, especialmente procurando avaliar o papel de óxido nítrico como agente citoprotetor. OBJETIVO: Estudar uma droga doadora de ácido nítrico - o dinitrato de isossorbida - e sua ação citoprotetora da mucosa gástrica de ratos submetidos ao tratamento com uma droga antiinflamatória - o cetoprofeno. MÉTODOS: Ratos machos adultos previamente submetidos a jejum de 24 horas, foram divididos em três grupos: a) grupo I (controle): animais, que receberam apenas solução salina isotônica via intragástrica, por gavagem e via endovenosa; b) grupo II (cetoprofeno-controle): animais que receberam solução salina via intragástrica por gavagem e cetoprofeno via endovenosa, e c) grupo III (nitrato/cetoprofeno): animais que receberam solução de 2 mM de dinitrato de isossorbida a via intragástrica por gavagem e cetoprofeno via endovenosa. Esses grupos foram, posteriormente, submetidos a exames macroscópico, microscópico e bioquímico, avaliando-se os seguintes parâmetros: a) determinação do índice de lesão gástrica; b) determinação da espessura da camada do muco secretor; c) determinação da concentração de ácido nítrico x tecidual, e d) determinação da concentração do malondialdeído tecidual. RESULTADOS: Encontrou-se menor índice de lesão gástrica nos animais do grupo III (nitrato), assim como maior espessura da camada do muco secretor nos animais deste grupo, do que nos animais do grupo II (cetoprofeno). A variação da concentração do ácido nítrico x tecidual foi semelhante nos três grupos. A taxa...

Helicobacter pylori and cagA gene detected by polymerase chain reaction in gastric biopsies: correlation with histological findings, proliferation and apoptosis

CONTEXTO E OBJETIVO: A virulência de Helicobacter pylori em doenças gastroduodenais está relacionada à presença de ilha de patogenicidade (cagPAI) que ocorre em algumas cepas. A infecção pelo cagPAI induz a secreção de IL-8, aumenta a proliferação epitelial, podendo ter um papel importante na carcinogênese. Nosso objetivo foi detectar HP e o gene cagA (marcador de cagPAI) pela técnica de PCR (polymerase chain reaction), correlacionando com os achados histológicos, de proliferação e apoptose. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo, no Laboratório de Patologia Cirúrgica e Molecular do Hospital Sírio Libanês. MÉTODOS: DNA isolado de 164 biópsias gástricas foi submetido a PCR para detecção de HP. Os casos positivos foram submetidos a nova reação para identificação do gene cagA. Pela técnica de imunohistoquímica foi analisada a proliferação celular e, pela TUNEL, a apoptose. RESULTADOS: HP foi detectado em 67,7% dos pacientes. Houve correlação entre a presença do HP e o diagnóstico de gastrite moderada ou grave, úlcera e linfoma do tipo MALT. Houve correlação entre cagPAI+ e a doença gástrica grave, incluindo o câncer. O risco de úlcera, adenocarcinoma ou linfoma MALT para os portadores de cagA+ foi de 8,8. Infecção pelo cagPAI correlacionou-se com aumento na taxa de proliferação. O índice proliferação/apoptose foi significantemente maior para os pacientes cagPAI+. CONCLUSÕES: Uma desregulação do crescimento celular nos pacientes cagPAI+ foi demonstrada pela diferença do índice de proliferação, que acreditamos pode explicar o papel carcinogênico da bactéria.

Double pylorus

Double pylorus (DP) or duplication of the pylorus is an uncommon condition that is either congenital or acquired. Acquired double pylorus (DP) results from a peptic ulcer eroding through and creating a fistula between the duodenal bulb and the distal stomach. We report a case of an acquired double pylorus in an adult gentleman that resulted from the erosion of a duodenal and prepyloric ulcer.

Doença de Crohn gastroduodenal-relato de quatro casos e revisao da literatura / Doença de Crohn gastroduodenal - relato de quatro casos e revisao da literatura

BACKGROUND: Crohn's disease can affect all the gastrointestinal tract, but gastroduodenal involvement is rarely seen (0.5 to 13 per cent). OBJECTIVES: Report clinical, radiological and endoscopic findings and treatment of four patients with gastroduodenal Crohn's disease and review the literature. PATIENTS AND METHODS: Four patients (one male of 24 years old three females of 37, 66 and 74 years old) with epigastric pain, weight loss and low grade fever were referred to the University Hospitals of Federal University of Rio de Janeiro and Fluminese Federal University. Two had also mild intermittent diarrhea and arthritis/arthralgia and the third developed pyloric obstruction and received surgical treatment. Anemia was observed in only one (the young female). Barium x-ray studies showed aphthous ulcers in stomach and duodenum with distal ileum lesions and deformity in both. Upper gastrointestinal endoscopy revealed aphthous ulcers in stomach and geographic duodenal ulcers. Polypoid lesions and serpiginous ulcers within gastric antrum were observed in the young female. Colonoscopy was performed in two patients and disclosed an ulcerated ileitis in one and ulcerated pancolitis in other. Histopathology findings of biopsy specimens were inconclusive (granulomas were not found) and other causes of granulomatous disease were ruled out. Corticosteroids and proton pump inhibitors were started and two patients had their disease controlled. The other patient developed pyloric obstruction and had to be operated. CONCLUSIONS: Gastroduodenal Crohn's disease has distinct clinical, therapeutic and prognostic features. Advances in endoscopic methods and recognition of new histopathologic criteria for diagnosis have revealed an incidence higher than previously reported.

Relevance of vacA Genotypes of Helicobacter pylori to cagA Status and Its Clinical Outcome

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 ; 76.9% versus 62.3% or 64.9%, res pectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.