Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores / Expression of RAGE in Helicobacter pylori infested gastric biopsies

Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

Comparative proteomics analysis of chronic atrophic gastritis: changes of protein expression in chronic atrophic gastritis without Helicobacter pylori infection

Chronic atrophic gastritis (CAG) is a very common gastritis and one of the major precursor lesions of gastric cancer, one of the most common cancers worldwide. The molecular mechanism underlying CAG is unclear, but its elucidation is essential for the prevention and early detection of gastric cancer and appropriate intervention. A combination of two-dimensional gel electrophoresis and mass spectrometry was used in the present study to analyze the differentially expressed proteins. Samples from 21 patients (9 females and 12 males; mean age: 61.8 years) were used. We identified 18 differentially expressed proteins in CAG compared with matched normal mucosa. Eight proteins were up-regulated and 10 down-regulated in CAG when compared with the same amounts of proteins in individually matched normal gastric mucosa. Two novel proteins, proteasome activator subunit 1 (PSME1), which was down-regulated in CAG, and ribosomal protein S12 (RPS12), which was up-regulated in CAG, were further investigated. Their expression was validated by Western blot and RT-PCR in 15 CAG samples matched with normal mucosa. The expression level of RPS12 was significantly higher in CAG than in matched normal gastric mucosa (P < 0.05). In contrast, the expression level of PSME1 in CAG was significantly lower than in matched normal gastric mucosa (P < 0.05). This study clearly demonstrated that there are some changes in protein expression between CAG and normal mucosa. In these changes, down-regulation of PSME1 and up-regulation of RPS12 could be involved in the development of CAG. Thus, the differentially expressed proteins might play important roles in CAG as functional molecules.

Localization of sugar residues in the stomach of three species of monkeys (Tupaiidae glis, Nycticebus cocang and Callithrix jacchus) by lectin histochemistry / Localización de los residuos de azúcar en el estómago de tres especies de monos (Tupaiidae glis, Nycticebus cocang y Callithrix jacchus) por histoquímica de lectina

The stomach of three species of non-human primates was investigated by lectin histochemistry to clarify the staining affinity and distribution patterns of their sugar residues. All gastric regions, with little differences between the deep and superficial parts of the same region, were rich in. in N-acetylglucosamine and/or neuraminic acid. Although, the superficial regions of the gastric mucosa were scanty in N-acetylgalactosamine, a- D-glucose and a -D-mannose, the deep parts of the gastric mucosa were rich in these sugars. In conclusion, there is a difference among the mucosubstances of surface and foveolar mucous cells, mucous neck cells, and gastric gland cells. This indicates heterogeneous composition of gastric mucus, or mucus molecules with variations in the degree of glycosylation of their oligosaccharide chains in the different cells which suggest that lectin binding affinity in the gastric mucosa correlated mostly to the degree of cellular differentiation.

El estómago de tres especies de primates no humanos fue investigado por histoquímica de lectinas para determinar la afinidad de tinción y los patrones de distribución de sus residuos de azúcar. Todas las regiones gástricas, con pequeñas diferencias entre las partes profundas y superficiales de la misma región, eran ricas en N-acetilglucosamina y/o ácido neuramínico. Si bien, las regiones superficiales de la mucosa gástrica eran escasas en N-acetilgalactosamina, a-D-glucosa y a-D-manosa, las partes profundas de la mucosa gástrica eran ricas en estos azúcares. En conclusión, existe una diferencia entre las mucosustancias de la superficie y células mucosas foveolares, células mucosas del cuello y células de las glándulas gástricas. Esto indica una composición heterogénea de la mucosa gástrica, o moléculas de moco con variaciones en el grado de glicosilación de sus cadenas de oligosacáridos en las diferentes células, sugieriendo que la afinidad de union de lectinas en la mucosa gástrica se relacionada principalmente con el grado de diferenciación celular.

Tissue quantification of neutral and acid mucins in the mucosa of the colon with and without fecal stream in rats / Quantificação tecidual de mucinas neutras e ácidas na mucosa do cólon com e sem trânsito intestinal em ratos

PURPOSE: To quantify the intensity of the expression of neutral and acids mucins in mucosa of the colon with and without fecal stream and to correlate this with the duration of fecal transit diversion. METHODS: Thirty male Wistar rats were subjected to fecal transit deviation in the left colon by a proximal colostomy and a distal mucous fistula. The animals were divided into three experimental groups, according to whether sacrificing would be performed six, 12 or 18 weeks after surgery. The expression of neutral and acid mucins was evaluated using the histochemical techniques of Periodic Acid Schiff and Alcian Blue, respectively. The tissue mucins expression was quantified by computer-assisted image analysis software (NIS-Elements) in the segments with and without fecal stream. Student's paired t test was used to compare the quantities of mucins in colon with or without fecal stream and variance between the experimental groups by ANOVA and Newman-Keuls post-test, establishing level of signification of 5 percent (p<0.05). RESULTS: There were significant decreased quantities of acid and neutral mucins in the colon without transit, compared with the colon with fecal stream, independent of the duration of exclusion. There was increased expression of neutral mucins in the colon with fecal stream after 12 and 18 weeks of exclusion. There was no increase in the expression of acid mucins in the colon with transit as the duration of fecal transit exclusion progressed. There was increased production of acid mucins in the animals submitted to diversion of the fecal stream for 18 weeks, compared with those subjected to diversion for 6 and 12 weeks. In the colon without fecal stream, there was increased expression of neutral mucins after 12 and 18 weeks of exclusion. CONCLUSIONS: Deviation of the fecal stream decreased the expression of acid and neutral mucins in the segments without fecal transit, compared with segments with transit. Regardless of ...

OBJETIVO: Quantificar a intensidade de expressão de mucinas neutras e ácidas na mucosa cólica provida e desprovida de trânsito intestinal relacionando-a ao tempo de exclusão fecal. MÉTODOS: Trinta ratos Wistar machos foram submetidos à derivação do trânsito no cólon esquerdo por colostomia proximal e fístula mucosa distal. Os animais foram divididos em três grupos experimentais segundo o sacrifício ter sido realizado seis, 12 e 18 semanas após a cirurgia. A avaliação da expressão de mucinas neutras e ácidas na mucosa cólica foi realizada com as técnicas histoquímicas do Periódico Ácido de Schiff e Azul de Alcian, respectivamente. A quantificação da expressão tecidual das mucinas foi com auxílio de programa de análise de imagem assistida por computador (NIS-Elements) nos segmentos providos e desprovidos de trânsito fecal. Utilizou-se o teste t de Student pareado na comparação da expressão de mucinas nos segmentos com e sem trânsito e a variação na expressão entre os grupos experimentais pelo teste ANOVA e pós-teste de Newmann-Keuls, estabelecendo-se nível de significância de 5 por cento (p<0,05). RESULTADOS: Houve redução na quantidade de mucinas neutras e ácidas no cólon desprovido de trânsito quando comparado ao cólon provido de trânsito, independente do tempo de exclusão. Ocorreu aumento na expressão de mucinas neutras no cólon provido de trânsito intestinal após 12 e 18 semanas de exclusão. Não houve aumento na expressão de mucinas ácidas no cólon provido de trânsito com o progredir do tempo exclusão de trânsito fecal. Ocorreu aumento na produção de mucinas ácidas nos segmentos com exclusão de trânsito por 18 semanas quando comparados aos animais submetidos à exclusão por seis e 12 semanas. No cólon desprovido de trânsito ocorreu aumento na expressão de mucinas neutras após 12 e 18 semanas de exclusão. CONCLUSÕES: A derivação do trânsito fecal diminui a expressão de mucinas ácidas e neutras nos segmentos desprovidos de trânsito fecal ...

Effect of pneumoperitoneum on cardiac output and gasrtic inramucosal PHi in obese and nonobese patients

This study was designed to investigate the effect of pneumoperitoneum [PP] on cardiac output [CO] and gastric intramucosal PHi [PHi is the predictor of splanchnic blood flow] in obese and non obese patients under general anesthesia. Thirty patients scheduled for laparoscopy cholecystectomy divided according to their body mass index >/= 30kg/m[2] obese and < 30kg/m[2] non- obese into 2 groups. After anesthesia and intubation, gastric tonometer catheter was inserted into the stomach and gastric intramucosal PHi was measured at 20 min after induction [baseline], 20 min after pneumoperitoneum [PP] and 15 mm after desuflation. Patients haemodynamic parameters were measured non invasively. Stroke volume [SV], heart rate [HR], cardiac output [CO] and mean arterial blood pressure [MABP] were recorded at 20min after induction [base line value], 2 and 20min after PP and 15min after desuflation. In this study we observed significant increase in MABP and HR in obese and non obese patients after PP. In both groups SV was significantly reduced after PP. Cardiac output [CO] was significantly increased at 2 and 20min after PP in obese patients while non obese patients experienced biphasic pattern in CO i.e. initial decrease at 2 min after PP., followed by gradual restoration of CO at 20mm after PP. At 15 min after desuflation CO started to return near to its base line value in both groups. The gastric intramucosal PHi mean values were insignificantly reduced at 20 min after PP and they were within the normal limit and start to return to its base line mean value at 15 min after desuflation in both obese and non obese patients. In conclusion pneumoperitoneum at 12minHg did not affect gasric intramucosal PHi i.e. splanchnic blood flow in obese and non obese patients. Moreover, the gastric intramucosal PHi was not affected by the changes in the cardiac output. Furthermore, obese patients well tolerated pneumoperitoneum without experiencing fall in cardiac output as that noticed in non obese patients who have a biphasic pattern of cardiac output during pneumoperitoneum [initial decrease followed by partial restoration and increase in CO]

Is regional tonometry a reliable index of tissue oxygenation? a comarative study with conventional global monitoring

This study was carried out on 30 critically ill patients admitted to the ICU of Farwania Hospital [Kuwait]. All patients had clinical evidence of organ dysfunction or impending multiple organ failure. The severity of their pathology on admission was assessed according to the APACHE II score. The study of each patient began after inserting the pulmonary artery catheter. The prospectively defined end-point of the study was the removal of the pulmonary artery catheter [72 hours] or death of the patient with the catheter in situ. The aim of the study was to determine the sensitivity and specificity of the intra-gastric mucosal pH [pHi] and other derived data in assessing the adequacy of tissue oxygenation, guiding therapy and prediction outcome. The results showed that pHi, pHa - pHi and PaCO2 - PO2 regional [reg] gradients were the most sensitive indices of tissue oxygenation and predictors of outcome. The mortality rate increased when pHi, PaCO2 - PCO2reg and pHa-pHi gradients were <7.3, > 10 mm Hg and <0.2 respectively. The derived variables obtained by invasive monitoring like base deficit [BD], lactate concentration in mixed venous blood [Lmv] and oxygn uptake index [02 UI] were valuable adjunct indices of tissue oxygenation. The risk of mortality increased when the BD was > - 5.5 +/- 1.2 meq.L -1, Lmv was> 4.5 +/- 1.2 mmol.L -1, and 02U1 was <100 +/- 6 ml.min -1 m -2. We recommend the use of gastric tonometry in routine ICU clinical practice

Diagnostic p53 expression in gastric endoscopic mucosal resection

Endoscopic mucosal resection (EMR) has been standardized for the treatment of intestinal type of intramucosal gastric carcinomas, and careful histological examination of the resected specimen is important for further treatment. To evaluate the diagnostic utility of p53 expression in gastric EMR samples, using immunohistochemical staining, we examined 24 gastric carcinomas (22 intestinal types and two diffuse types) and 20 adenomas removed by EMR. Intestinal type of adenocarcinomas revealed strong p53 expression in 13 cases (59%), weak in four cases (18%), and negative in five cases (23%). Resection margins of 11 carcinomas were involved in the carcinoma cells, which showed the same p53 expression pattern with main carcinoma cells. Squeezed carcinoma cells, remaining in resection margins, were definitely identified by strong p53 expression in seven cases of which the main tumor strongly expressed p53. Microscopic in situ carcinoma could be easily detected in p53 immunostaining. Multifocal involvement and submucosal invasion of carcinomas could be demarcated easily and definitely by strong p53 expression of carcinoma cells. All adenomas showed diffuse weak p53 expression. The difference of p53 expression (p< 0.001) could be used as a differential diagnosis between adenomas and carcinomas. According to these results, we propose that for careful histological examination in hospital diagnosis, both histological evaluation and p53 immunostaining are important diagnostic parameters in EMR samples of the intestinal type of gastric carcinomas.

Refluxo duodenogástrico em portadores de colecistolitíase, antes e após a colecistectomia, e prevalência do "Helicobacter pylori" no antro gástrico / Duodenal gastric reflux in cholecystoletiasis carrier state, before and after cholecystectomy, and prevalence of helicobacter pylori in gastric antrum

Foram estudados 34 portadores de litíase vesicular. Verificou-se a prevalência do refluxo duodenogástrico e da colonizaçäo pelo Helicobacter pylori no antro gástrico, antes e após a colecistectomia. No somatório dos casos do pré e pós-operatório foi determinado se a presença de bile refluída para o estômago portador do Helicobacter pylori modificava a prevalência deste no antro gástrico. Concluiu-se que, quando havia bile no estômago, houve diminuiçäo significante na prevalência do Helicobacter pylori no antro gástrico (p<0,05).

Bauhinia purpurea agglutinin (BPA) binding sites in human gastrointestinal tract.

The binding of biotinylated BPA to parraffin sections of 18 normal gastrointestinal tract mucosa, 5 nonneoplastic polyps (NNP), 12 adenomas, and 59 carcinomas was studied by using avidinbiotin peroxidase complex (ABC) technique. In normal mucosa BPA appeared to bind both mucus and nonmucus glycoproteins but goblet cell mucus showed a decrease in binding and increase in binding of nonmucus glycoproteins as the cells lose their differentiation. BPA showed characteristic binding patterns in adenoma and carcinoma that differed from the pattern in normal mucosa. In normal mucosa linear binding to the apical cytoplasm in the columnar cells of the surface epithelium was observed, whereas in adenomas and carcinomas, in addition to the linear binding to the apical cytoplasm, diffuse cytoplasmic and granular deposits in the supranuclear, paranuclear or infranuclear zones were seen. Our findings suggest that BPA binding patterns in normal and neoplastic mucosa are related to the degree of cellular differentiation. In the process of malignant transformation the carbohydrate distribution undergoes progressive changes through the adenoma carcinoma sequence. These changes are related to the degree of dysplasia in adenomas and to the degree of differentiation in carcinomas.

Distribuiçäo das células endócrinas do estômago do gambá Didelphis albiventris: estudo histoquímico / Distribution of endocrine cells in the stomach of the white-belly opossum Didelphis albiventris: a histochemical study

As células endócrinas do estômago do gambá Didelphis albiventris foram demonstradas, empregando-se métodos histoquímicos seletivos. Quatro tipos celulares foram detectados de acordo com a reatividade aos métodos usados, destacando-se o método de Grimelius, que permitiu uma melhor caracterizaçäo morfológica, bem como revelou um maior número de células. As reaçöes positivas aos métodos da hematoxilina plúmbica e da metacromasia mascarada com hidrólise prévia pelo ácido clorídrico säo índices histoquímicos da presença de proteínas da classe das cromograninas

Investigaciones de los neurotransmisores 5-hidroxitriptamina, noradrenalina y dopamina, en mucosa gastroduodenal: correlación clínica e histológica / Determination of the neurotransmitters 5-hydroxytryptamine, noradrenaline, and dopamine in gastroduodenal mucosa: clinical and histologic correlation

Se estudiaron las concentraciones (pg/mg de tejido de los neurotransmisores (NT) 5-Hidroxitriptamina (5HT), Noradrenalina (NA) y Dopamina (DA) en mucosa del fundus gástrico (F), antro (A) y bulbo duodenal (D) de 21 paciente con mucosa normal y con diversos grados de inflamación crónica. Se correlacionaron las concentraciones de los NT entre sí, en conjuntos en cada región y con parámetros clínicos, de motilidad indirectos e histológicos. Los valores promedios hallados en cada región fueron para 5HT: F=940+/-457, en A=787+/-407 y en D=601+/-272; para NA en F=217+/-138, en A=228+/-126 y en D=245+/-118; y para DA en F=50+/-32, en A=46+/-31 y en D=53+/-45. Se observó que a mayores infiltrados inflamatorios en bulbo duodenal se encontraron mayores concentraciones de DA (r=0,94). Ningún otro parámetro tuvo relación significativa con las variaciones de los NT. Se pudo establecer que las variaciones de las concentraciones de los NT de la mucosa del antro gástrico están más asociadas a las del bulbo duodenal que a las del fundus gástrico

Níveis teciduais da prostaglandina 6-ceto-pgf 1a e integridade da mucosa gástrica em pacientes com doença de Chagas / Tissue levels of 6-ketoprostaglandin F1 alpha and integrity of gastric mucosa in patients with Chagas disease

Foram estudados 14 pacientes com a forma digestiva da doença de Chagas manifestada por megaesôfago e/ou megacolón com sorologia positiva para a doença de Chagas e 10 indivíduos näo chagásicos. Todos os pacientes foram submetidos à endoscopia digestiva alta para diagnósticos e colheita de biópsia de antro para estudo histopatológico e dosagem da prostaglandina 6-ceto PGF1 alfa. Houve maior freqüência de gastrite moderada e intensa no grupo chagásico do que no grupo controle. Os níveis de 6-ceto-PGF alfa no grupo chagásico variou de 36,5 a 245,6 ng/g (mediana: 80,75 ng/g) e näo foram estatisticametne diferentes (p>0,10) dos níveis encontrados no grupo controle, que variou de 13,1 a 269,6 ng/g (mediana: 116,2 ng/g). Estes resultados näo apoiam a idéia de que a desenervaçäo intramural do estômago na doença de Chagas esteja associada à reduçäo da síntese local de prostaglandinas

Immunohistochemical localization of insulin-like materials in antral gastric mucosa and intestinal epithelial cells of the turtles Chrysemys dorbigni and Phrynopshilarii

Immunoreactive insulinwas demonstrated immunohistochemically with antibodies to human and porcine insulin by the avidin-biotin-peroxidase complex method in open-type gastrointestinal cells from sections of the antral stomach and of the upper, midle and lower intestine of the turtles Chrysemys dorbigni and Phrynops hilarii.In both species the concentration of cells positive for insulin-like material was higher in the gastric antrummthan in the gut.The localization of insulin-like material in gastrointestinal mucosal cells of turtles is an unusual finding among vertebrates, because the insulin-containing cells migrate from the mucosal epithelium of the intestine early in vertebrate evolution to the acinar pancreas.The chemical nature of the gastrointestinal insulin-like material and its physiological role remainm to be determined