Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Effects of prokinetic drugs on the abdominal wall wound healing of rats submitted to segmental colectomy and colonic anastomosis / Efeitos de drogas procinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo

PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.

OBJETIVO: Avaliar os efeitos do uso de drogas prócinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo. MÉTODOS: Foram utilizados 60 ratos, alocados aleatoriamente em três grupos para receberem as seguintes medicações no período pós-operatório: M (metoclopramida); B (bromoprida) e C (solução salina a 0,9%). Os procedimentos cirúrgicos foram idênticos em todos os animais. Foi realizada laparotomia mediana, seguida de colectomia segmentar de 1-cm e anastomose colônica. O fechamento da parede abdominal foi feito em dois planos de sutura contínua. No 3° ou no 7° dia pós-operatório foram coletadas amostras da parede abdominal para medida da força de ruptura e avaliação histopatológica. RESULTADOS: Não houve diferença significativa entre os grupos no que diz respeito à força de ruptura da parede abdominal, nem entre os subgrupos no 3º e 7º dia após a cirurgia. À análise histopatológica não houve alterações na deposição de colágeno ou na quantidade de fibroblastos no sítio da cicatriz. CONCLUSÃO: O uso de drogas prócinéticas, metoclopramida ou de bromoprida, não interferiu na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo.

Motilidad intestinal y microflora / Intestinal motility and microflora

La microflora es el conjunto de colonias microbacterianas que cubren la superficie del tubo digestivo. Cada sujeto humano alberga unos 100 billones de colonias de unas 400 especies distintas, biodiversidad que facilita la vida y el desarrollo del conjunto. La concentración de bacterias va aumentando a lo largo del tubo digestivo, alcanzando concentraciones de 1012 UFC/ml. en el colon. La motilidad del intestino delgado es propulsiva con una fase de barrido que no permite el crecimiento de bacterias. Por el contrario, la motilidad del colon es muy lenta y no propulsiva durante el ayuno y el sueño. Sólo en vigilia y en período postprandial existen ondas de contracción de alta amplitud y rápidamente progresivas en dirección oral-anal. La interacción entre las bacterias presentes en el lumen y las ondas de contracción motora es muy difícil de evaluar. Este efecto se ha estudiado en base a los fármacos que alteran la motilidad y que al aumentar ésta, barren con la flora bacteriana presente. En ese sentido se sabe que el uso de cisaprida acelera el tránsito, reduciendo la densidad de bacterias metanogénicas con un aumento de la excreción de hidrógeno. En cambio, loperamida disminuye el tránsito, aumentando la flora metanogénica (hecho que representa lo que sucede a pacientes constipadas, que tienen flora mayoritariamente productora de metano). Conclusión: La interacción entre motilidad y flora bacteriana es compleja y está poco estudiada fundamentalmente debido a dificultades técnicas.

Microflora is the set of microbacterium colonies covering the digestive tract surface. Each human subject hosts ca. 100 billions of colonies of 400 different species, b23wiodiversity that facilitates life and development of the whole. Bacteria concentration increases throughout the digestive tract, reaching concentrations of 1012 CFU/ml in the colon. Motility of the small intestine is propulsive with a sweeping phase, allowing for the growth of bacteria. On the contrary, motility of the colon is very slow and non-propulsive during fasting and sleeping. Only during wakefulness and postprandial period there are wide-ranging and quickly progressive contraction waves in oral-anal direction. Interaction between bacteria present in lumen and the contraction waves is very hard to assess. This effect has been studied based on drugs that alter motility, and when it increases, they sweep the existing gut flora. In this sense, it is known that the use of cisapride accelerates the transit, reducing the density of methanogenic bacteria with an increase in the hydrogen excretion. On the other hand, loperamide slows down transit, causing an increase of the methanogenic flora (which represents what happens to constipated patients with flora that produces mainly methane). Conclusion: Interaction between motility and gut flora is complex and has not been enough studied mainly due to technical difficulties.

Endoscopic Evaluation of Gastric Emptying and Effect of Mosapride Citrate on Gastric Emptying

PURPOSE: Gastric emptying has been evaluated by scintigraphy in spite of its limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a simple technique, however, its validation for gastric emptying and quantification of food has not yet been investigated. The aim of our study was to assess endoscopic gastric emptying compared with scintigraphy and radiopaque markers (ROMs) studies. We also investigated the effect of a single dose of mosapride on gastric emptying. MATERIALS AND METHODS: Fifteen healthy volunteers underwent scintigraphy. Next day, subjects received a standard solid meal with ROMs and underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the same procedure was repeated after ingestion of mosapride (5 mg for group 1, n = 8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric residue by endoscopy was scored from 0 to 3, and the scores were added up. RESULTS: All subjects completed the study without any complication. The gastric emptying rate [T1/2 (min)] was in normal range (65.6 +/- 12.6 min). Endoscopic gastric emptying was correlated significantly with gastric clearance of ROMs (r = 0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs after administration of mosapride showed significant differences in the 10 mg group (p < 0.05). CONCLUSION: Endoscopy can evaluate gastric emptying safely and simply on an outpatient basis. A 10 mg dose of mosapride enhanced gastric emptying, assessed by both endoscopy and ROMs.

Effects of mosapride on motility of the small intestine and caecum in normal horses after jejunocaecostomy

The purpose of the present study was to evaluate the prokinetic effects of mosapride with non-invasive assessment of myoelectrical activity in the small intestine and caecum of healthy horses after jejunocaecostomy. Six horses underwent celiotomy and jejunocaecostomy, and were treated with mosapride (treated group) at 1.5 mg/kg per osos once daily for 5 days after surgery. The other six horses did not receive treatment and were used as controls (non-treated group). The electrointestinography (EIG) maximum amplitude was used to measure intestinal motility. Motility significantly decreased following surgery. In the treated group, the EIG maximum amplitude of the small intestine was significantly higher than in the controls from day 6~31 after treatment. These findings clearly indicate that mosapride could overcome the decline of intestinal motility after jejunocaecostomy in normal horses.

Isolation of a haemorrhagic protein toxin (SA-HT) from the Indian venomous butterfish (Scatophagus argus, Linn) sting extract.

A haemorrhagic protein toxin (SA-HT) was isolated and purified from the spine extract of the Indian venomous butterfish, S. argus Linn, by two step ion exchange chromatography. The toxin was homogeneous in native and SDS-PAGE gel. SDS-molecular weight of the toxin was found to be 18.1 +/- 0.09 kDa. SA-HT produced severe haemorrhage on stomach wall but devoid of cutaneous haemorrhage. UV, EDTA, trypsin, protease, cyproheptadine, indomethacin, acetylsalicylic acid and BW755C treatment significantly antagonized the haemorrhagic activity of SA-HT. The toxin produced dose and time dependent oedema on mice hind paw, which was significantly encountered by cyproheptadine, indomethacin and BW755C. SA-HT increased capillary permeability on guinea pig dorsal flank. On isolated guineapig ileum, rat fundus and uterus, SA-HT produced slow contraction which was completely antagonised by prostaglandin blocker SC19220. On isolated rat duodenum, SA-HT produced slow relaxation. SA-HT significantly increased plasma plasmin, serum MDA level and decreased serum SOD level indicating the possible involvement of cyclooxygenase and lipooxygenase pathway.

Investigation into the Effects of Mosapride on Motility of Guinea Pig Stomach, Ileum, and Colon

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.

Effect of erythromycin and cisapride on emptying of the vagally denervated intrathoracic stomach.

BACKGROUND: Subsequent to esophagectomy and reconstruction among patients with esophageal cancers, the intrathoracic denervated stomach acts as a passive conduit without peristalsis. OBJECTIVE: The study was designed to assess the impact of two prokinetic drugs viz. erythromycin and cisapride on the emptying of vagally denervated intrathoracic stomach. METHODS: Twenty consecutive patients of carcinoma esophagus, who had undergone one stage transhiatal oesophagectomy with cervical esophagogastrostomy and were disease free at three months postoperative follow-up, were included in the study. These patients were randomised into two groups of ten each. The patients in group A received erythromycin, while patients in group B received cisapride. The gastric emptying was studied by scintigraphy, using a standard test meal containing 99m Tc sulphur colloid labelled 'IDLIS' [rice based radio labelled food] before and after the drug treatment. RESULTS: The pre and post treatment mean gastric half emptying time of the patients in the erythromycin group was 52.6 min and 49.7 min (p > 0.1) and in cisapride group it was 53.76 and 26.4 min respectively (p < 0.05). Intergroup comparison of the difference was not statistically significant. CONCLUSION: Cisapride is an effective prokinetic agent in the treatment of gastric stasis of the vagally denervated intrathoracic stomach.

Effects of piperitenone oxide on the intestinal smooth muscle of the guinea pig

We investigated the effects of piperitenone oxide (PO), a major constituent of the essential oil of Mentha x villosa, on the guinea pig ileum. PO (30 to 740 mug/ml) relaxed basal tonus without significantly alterating the resting membrane potential. In addition, PO relaxed preparations precontracted with either 60 mM K+ or 5 mM tetraethyl-ammonium in a concentration-dependent manner. At concentrations from 0.1 to 10 mug/ml PO potentiated acetylcholine-induced contractions, while higher concentrations (>30 mug/ml) blocked this response. These higher PO concentrations also inhibited contractions induced by 60 mM K+. PO also blocked the components of acetylcholine contraction which are not sensitive to nifedipine or to solutions with nominal zero Ca2+ and EGTA. These results show that PO is a relaxant of intestinal smooth muscle and suggest that this activity may be mediated at least in part by an intracellular effect.

The influence of gastrokinetics and inhibitors of acid secretion on motor responses of the gastric fundus to acetylcholine

The influence of eight gastrokinetics and six inhibitors of acid secretion used routinely in gastrointestinal prescriptions were verified, through dose-response curves to acetylcholine, on longitudinal muscular gastric fundus secretions of 70 rats. Some drugs increased the fundic motor response, and few others decreased the affinity of the fundi for acetylcholine. The results of the present paper may contribute to the knowledge of the effect of these drugs on gastric motility

Inhibition of gastric secretion by a water extract from Baccharis triptera, Mart

Baccharus triptera Mart, is a widespread Compositae used in Brazilian folk medicine to treat gastrointestinal disturbances, rheumatic disease, mild fever, diabetes and as an anti-helminthic. Water extract of small branches of the plant (WE) administered to mice and rats (0.1 to 2 g/Kg, p.o) did not alter spontaneous motor activity, sleeping time induced by barbiturates or the tailflick response in mice. The extract decreased by 40 por cento the number of writhings induced by 0.8 por cento scetic acid, i.p., but did not influence paw edema induced by carrageenan or dextran in rats WE (2g/Kg, p.o.) decreased the intestinal transit of charcoal in mice by 20//. Gastric secretion in pylorus ligated rats was reduced after treatment with WE (1 and 2 g/Kg. i.p. or intraduodenal and the gastric pH was raised. The extract (1 g/Kg, p.o.) prevented gastric ulcers induced in rats by immobilization at 4ºC, but not those induced by indomethacin (10 mg/Kg, s.c.). The results indicate that WE may relieve gastrointestinal disorders by reducing acid secretion and gastrointestinal hiperactivity. Neither analgesic nor anti-inflammatory activities were detectable. .