Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer

Aim of the study: Mouriri pusa, popularly known as manapuca or jaboticaba do mato, is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects.Materials and methods: The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid.Results: In the acute model, treatment with either, TF (25 mg/kg) or FF (50 mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers' regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed.Conclusions: Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety. (C) 2010 Elsevier B.V. All rights reserved.

Abarema cochliacarpos: Gastroprotective and ulcer-healing activities

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Úlcera gastroduodenal em potros

Dentre as inúmeras patologias que acometem os eqüinos jovens, as úlceras gástricas situam-se como uma das mais importantes. MURRAY et al. (1987) trabalhando com potros clinicamente normais, constatou uma prevalência de úlceras da ordem de 51%. O mesmo autor realizando gastroscopia em 45 equinos com idade entre 1 e 24 anos, observou a presença de úlceras em 93% dos animais (MURRAY, 1988). de etiologia não completamente definida, acredita-se que inúmeros fatores estejam envolvidos na gênese das úlceras gastroduodenais, sendo o estresse um dos mais importantes. Um desequilíbrio entre os fatores de agressão e proteção da mucosa gástrica é sugerido, onde uma vez ocorrendo o predomínio dos fatores de agressão, a formação das úlceras estaria determinada. de acordo com o tipo, presença ou ausência de sinais clínicos, localização das lesões na mucosa gástrica e possíveis complicações de sua ocorrência, quatro síndromes clínicas são reconhecidas em potros: 1) úlceras assintomáticas ou silenciosas; 2) úlceras sintomáticas ou ativas; 3) úlceras perfuradas e, 4) obstrução gástrica ou duodenal. O diagnóstico deve ser baseado na história clínica, sinais clínicos, resposta à terapia e principalmente nos achados do exame gastroscópico. O tratamento pode ser feito utilizando-se drogas inibidoras da secreção ácida, protetores de mucosas, anti-ácidos, análogos da prostaglandina e estimulantes de motilidade intestinal. Quando indicado emprega-se o tratamento cirúrgico.

Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs

Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known in Brazil as chanana. This species is distributed from Guyana to southern Brazil where it is considered a weed. The plant occurs in tropical rain forest, fields, and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric dysfunction including gastric and duodenal ulcers. In this study, the ability of a lyophilized infusion, as an aqueous fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa was examined in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration by 39% and 46%, respectively, at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the incidence of gastric lesions induced by a combination of indomethacin and bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric ligature experiment showed that the highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH from 2.5 (control) to 5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF had no significant effect on duodenal ulcers induced by cysteamine. Preliminary phytochemical screening confirmed that flavonoids were the major constituents of the AqF of T. ulmifolia. These results indicate that this extract has a significant antiulcerogenic effect, as popularly believed.

Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice

Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCI/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCI/EtOH-induced gastriculcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p < 0.000 1). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p < 0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p < 0.0001), increased pH values and promoted reduced acid output (p < 0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p > 0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action. (c) 2004 Elsevier GmbH. All rights reserved.

Response to Treatment in a Prospective Cohort of Patients with Large Ulcerated Lesions Suspected to Be Buruli Ulcer (Mycobacterium ulcerans Disease)

Background: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called Buruli ulcer'' (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of >= 10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC).Methods: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment.Findings: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%).Interpretation: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed.

Transplante pancreato-duodenal em ratos com microcirurgia. A téchnica e os resultados após 12 anos de experimentação

In this study we present the technical details, adaptations and modifications of the original procedure of pancreaticoduodenal transplantation in rats described by Lee et al. in 1972. We also present the results and technical failures observed in a follow-up of 12 years. From March, 1982 to December, 1994, we performed in the Laboratory of Surgical Technique and Experimental Surgery of Faculty of Medicine, Botucatu - UNESP, Brazil, 665 duodenopancreatectomies in donor rats and 592 surgeries for revascularization of the pancreatic graft in recipient animals. The observed percentage of technical failures in donor rats was 11% due to bleeding and/or vascular complications, irregular flushing of the graft with saline and respiratory insufficiency. In recipients of grafts, we observed a percentage of technical failures of 22,5% due to porto-caval thrombosis, vascular bleeding, pancreatitis and graft ischemia. In both surgeries, the successful results are directly related to the technical performance of the surgeon and the cares in the postoperative period.

Genetic alterations in benign lesions: Chronic gastritis and gastric ulcer

Aim: To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TP53 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. Methods: Gastric biopsies from normal mucosa (NM, n = 10), chronic gastritis (CG, n = 38), atrophic gastritis (CAG, n = 13) and gastric ulcer (GU, n = 21) were studied using fluorescence in situ hybridization (FISH) and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect H pylori. An association of the gastric pathologies and aneuploidies with H pylori infection was assessed. Results: Aneuploidies were increasingly found from CG (21%) to CAG (31%) and to GU (62%), involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG (P = 0.0143) and GU (P = 0.0498). No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% (5/11) and 12% (2/17) of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. Conclusion: The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with H pylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa. © 2006 The WJG Press. All rights reserved.

Diferentes procedimentos na determinação de indicadores internos para estimativa de produção fecal e fluxo duodenal de matéria seca em bovinos

Times of in situ incubation (144 and 288h) for determination of internal markers IADF and INDF and the effects of differents procedures (wash or not the nylon bag every 72h incubation) was evaluated in samples of diet, duodenal digesta and cattle feces. The duodenal flow dry matter and fecal production utilizing the internal markers to compare with the external marker chromium oxide there was estimated. The animals were fed with sorgum silage, concentrate or urea. In this experiment, a latin square design was used, in a factorial scheme (two times of incubation × two processing nylon bag). No was observed effect of the incubation time or processing in the internal markers INDF and IADF concentration and the in situ incubation after 144h is adequate to reproduce the indigestible markers fraction in samples. For fecal production estimation, the external marker chromium oxide presented similar result (1.26 kg day-1) as the total fecal collection (1.49 kg day-1). Both the internal markers overestimate the duodenal flow dry matter when compared with the external marker chromium oxide.

Effects of the ethyl acetate fraction of Alchornea triplinervia on healing gastric ulcer in rats

Alchornea triplinervia (Spreng.) Muell. Arg (Euphorbiaceae) is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. We previously described the gastroprotective action of methanolic extract (ME) of Alchornea triplinervia and the ethyl acetate fraction (EAF) in increasing of prostaglandin E 2 (PGE 2) gastric levels in the mucosa. In this work we evaluated the effect of EAF in promoting the healing process in rats with acetic acid-induced gastric ulcers. In addition, toxicity was investigated during treatment with EAF. After 14 days of treatment with EAF, the potent stimulator of gastric cell proliferation contributed to the acceleration of gastric ulcer healing. Upon immunohistochemical analysis, we observed a pronounced expression of COX-2, mainly in the submucosal layer. The 14-day EAF treatment also significantly increased the number of neutrophils in the gastric mucosa regeneration area. The EAF induced angiogenesis on gastric mucosa, observed as an increase of the number of blood vessels supplying the stomach in rats treated with EAF. Oral administration for 14 days of the ethyl acetate fraction from Alchornea triplinervia accelerated the healing of gastric ulcers in rats by promoting epithelial cell proliferation, increasing the number of neutrophils and stimulation of mucus production. This fraction, which contained mainly phenolic compounds, contributed to gastric mucosa healing. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Desempenho e morfometria duodenal de frangos de corte submetidos a diferentes níveis de energia e programas de alimentação de 42 a 57 dias de idade

This experiment was conducted to evaluate the use of different energy levels and amino acid recommendations on performance, carcass yield and intestinal morphometry of broilers from 42 to 57 days of age. We used 1,600 one-day old male broilers (Cobb 500) in a completely randomized design arranged in a 2x4 factorial scheme with 3,200 and 3,600 kcal ME/kg and four different feed programs. The metabolizable energy levels and the feed programs did not determine significant differences in carcass characteristics for choosing a level of energy or a feed program, thus the energy level and the recommendations of amino acids that determine the highest cost-benefit ratio should prevail. It was observed that 3,600 kcal ME/kg resulted in some improvement on performance and morphometry of the intestinal mucosa, also the fractioning of digestible amino acid requirements during two periods resulted in worse performance and intestinal villi height.

Essential oils from medicinal and aromatic plants: A review of the gastroprotective and ulcer-healing activities

Gastric ulcer is an excoriated area of the gastric mucosa. It is among the predominant gastrointestinal chronic diseases. The essential oils represent an important part of the traditional pharmacopoeia in many countries and have been successfully used for gastroprotection and ulcer healing. Thus, this review presents the experimental activity of essential oils traditionally used in the gastric ulcer prevention and treatment, considering their families, part of the plant studied, bioassays, and their mechanisms of gastroprotection and ulcer healing, with the aim of stimulating novel studies in the search for a new phytomedicine to treat gastric diseases. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.