Pharmacological efficacy of argemone mexicana plant extract, against cysteamine-induced duodenal ulceration in rats.

Objective: The plant Argemone mexicana is traditionally used as diuretic, anti-inflammatory, antibacterial, antifungal agent, and has wound-healing property. This study was carried out to evaluate the effect of A. mexicana aerial part of the plant (methanolic and aqueous extract p.o.) on duodenal ulceration. Materials and Methods: The study was carried out on the duodenal ulceration model by using cysteamine hydrochloride. Ranitidine (20 mg/kg) was used as standard drug. Results: Both the extracts of the plant A. mexicana produced a significant activity in cysteamine-induced duodenal ulceration. The aqueous extract at the dose-dependent manner showed the potent activity than methanolic extract. Conclusion: The plant A. mexicana Linn. Increased healing of gastric ulceration and prevented the development of experimentally induced duodenal ulceration in rats.

Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 microg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

The use of nonsteroidal anti-inflammatory drugs and the occurrence of gastric lesions among patients undergoing upper endoscopy in a university hospital in Brazil

BACKGROUND: Nonsteroidal anti-inflammatory drugs are widely used in Brazil in spite of the known risks associated with their use, but investigation of their side effects conducted in this country has been far from sufficient. This study investigates the use of NSAIDs among patients undergoing upper endoscopy in the Hospital das Clínicas of the Federal University of Minas Gerais and the association of this use with the endoscopic diagnosis of gastric erosions, gastric erosions with hematin pigmentation, and gastric ulcer. METHODS: The cross-sectional methodological approach was used; 533 patients aged 17 or older were interviewed, between June and December, 2000. Data were submitted to bivariate and multivariate analyses. RESULTS: More than two thirds of the interviewed population reported the use of nonsteroidal anti-inflammatory drugs in a period of 1 month before the upper endoscopy. The most used nonsteroidal anti-inflammatory drugs were acetylsalicylic acid and diclofenac. An association was clearly shown between the use of these drugs and the occurrence of the studied lesions, with the latter attaining significance. There was also a significant association between nonsteroidal anti-inflammatory drugs use for a period greater than 15 days and the occurrence of the gastric lesions, with a higher odds ratio than for the other comparisons. CONCLUSIONS: The results suggest that nonsteroidal anti-inflammatory drugs have a significant association with the occurrence of the gastric lesions and point to the need of further study of this issue in Brazil.

INTRODUÇÃO: No Brasil são bastante evidentes os riscos associados ao uso de medicamentos. No entanto, tal questão não é devidamente privilegiada no campo da investigação científica. O presente estudo se refere ao uso de antiinflamatórios não-esteróides, fármacos amplamente utilizados no país. O objetivo foi investigar o uso de antiinflamatórios não-esteróides entre pacientes submetidos à endoscopia digestiva alta no Hospital das Clínicas da Universidade Federal de Minas Gerais e sua associação com a ocorrência de erosões gástricas, erosões gástricas com pigmento de hematina e úlcera gástrica. MÉTODOS: Estudo transversal em que 533 pacientes com idade igual ou superior a 17 anos foram entrevistados no período de junho a dezembro de 2000. Os dados foram submetidos às análises bivariada e multivariada. RESULTADOS: Mais de dois terços da população entrevistada relatou o uso de antiinflamatórios não-esteróides no período de um mês anterior à endoscopia digestiva alta. Os antiinflamatórios mais utilizados foram o ácido acetilsalicílico e o diclofenaco. Evidenciou-se uma associação positiva e significativa entre o uso desses fármacos e a ocorrência das lesões em questão. Ao se avaliar a associação entre o uso de antiinflamatórios não-esteróides por um período superior a 15 dias e a ocorrência das lesões gástricas, esta foi positiva e significativa, apresentado odds ratio superiores àqueles apresentados para as associações anteriores. CONCLUSÕES: Os resultados sugerem que os antiinflamatórios não-esteróides têm uma associação significativa com a ocorrência de lesões gástricas e apontam para a necessidade de aprofundamento no estudo desta questão no Brasil.

Histological changes in parts of forgut of rat after indomethacin administration

Indomethacin, a non-steriodalanti-inflammatory drug, is used mainly for the treatment of painful joints such as rehumatoid arthritis, osteo'arhtritis, gout, ankylosing spondylitis etc. It relieves pain, reduces swelling and tenderness of the joints. It also induces ulceration of stomach and small intestine both in experimental animals and humans. In this study indomethacin was given intrapertioneally in maximum therapeutic dose [4 mg/Kg body weight] to three experimental groups B, C and D for one, two and three weeks respectively. Group A was the control group. Effects were observed in stomach pylorus and proximal duodenum. In the stomach pylorus, well defined superficial ulcers were identified during initial two weeks of drug administration. The ulcer penetrated as for as muscularis mucosae and ulcer bed had coagulative necrosis and inflammatory cells. During third week, stomach pylorus showed minor damage in the form of focal necrosis. Duodenum was affected less than stomach and showed villi with lost tips, tilted and distorted villi. Morphometric analysis showed changes in stomach pylorus and in duodenum. The number of mitotic figure was significantly increased in stomach pylorus. Duodenum showed insignificant to significant decrease in the height of villi. Increase in the number of goblet cells, columnar cells, and mitotic figure was also noted; which was undoubtedly part of the tissue response to an injury. These observations suggested that indomethacin given in a ma ximum therapeutic dose, initially induces lesions in stomach pylorus and proximal duodenum but almost no effects were noted when duration of the drug administration was prolonged

Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and healing in experimental NIDDM rats.

Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AIE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats.

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats.

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.

Effect of pirenzepine [gastrozepin] on the induced duodenal ulcer by aspirin in albino rat

Adult albino rats kept on standard diet and water were divided into 2 main groups: The first group served as control group, animals were sacrificed after 6 weeks. The second group received a daily oral dose of acetyl salicylic acid [aspirin] 100 mg/kg body weight/day for 6 weeks. The duodenum from all animals were processed to paraffin sections. They were stained with H and F, periodic acid-Schiff's reaction, Alcian blue, Bodian technique and Masson's trichrome stain. Parts of the duodenum were cryostate cut, stained with Gomori's technique for acid phosphate. On aspirin administration, there was discontinuity and loss of the lining epithelium at the top of the villi. Some epithelial cells were undergoing degeneration with decrease in heights. The brush border was interrupted. PAS demonstrated apparent increase in goblet cells, while Alcian blue stained sections appeared paler blue. Acid phosphatase reaction was increased. The lamina propria appeared disorganized with no evidence of fibrosis. Mitotic figures were increased in the base of the crypts. On pirenzepine administration, the duodenum appeared normal resembling control. The villous tips appeared intact. The brush border regained its continuity, goblet cells were apparently decreased reaching control level, while Alcian blue showed increased intensity. The acid phosphatase reaction was reduced

Effect of ayurvedic medicines on beta-glucuronidase activity of Brunner's glands during recovery from cysteamine induced duodenal ulcers in rats.

Biochemical and histochemical studies revealed decreased beta-glucuronidase activity in the Brunner's glands of duodenal ulcerated rats. The enzyme activity showed gradual increase during recovery. Rats treated with a mixture of Ayurvedic medicines (Glycyrrhiza glabra, Terminalia chebula, Piper longum and Shanka Bhasma) recovered faster with concomitant increase in beta-glucuronidase activity in the Brunner's glands. It can be concluded that Ayurvedic medicines used do not act as antacid but improve the secretory status of Brunner's glands involved in the protection against duodenal ulcer.

The effect of verapamil on cysteamine-induced duodenal ulcer in the rat

To determine the effect of verapamil on experimental duodenal ulcer, pathologic assessment and secretory study were performed in the rats with ulcerogenic dose of cysteamine. The cysteamine increased gastric acid secretion and produced double duodenal ulcers at the proximal protion of the duodenum. Intramuscular injection of verapamil, 3 hours later, produced a significant decreased in gastric acid secretion which lasted at least 4 hours (cysteamine vs. cysteamine+ verapamil; 63.5 +/- 18.4 muEq vs. 25.5 +/- 9.0 muEq during the 1st hour after verapamil administration, 83.1 +/- 24.2 muEq vs. 27.8 +/- 12.3 muEq during the 2nd hour, 110.9 +/- 14.4 muEq vs. 38.5 +/- 25.9 muEq during the 3rd hour, 116.4 +/- 12.1 muEq vs. 40.7 +/- 29.6 muEq during the 4th hour, p less than 0.001). However, cysteamine-induced duodenal ulcers were not alleviated by two doses of intramuscular verapamil administration (4 mg/kg x 2). It is presumed that suppression of gastric acid secretion may not be sufficient to reduce cysteamine-induced duodenal ulcer formation or that verapamil itself may have aggresive effects against duodenum. To illucidate the exact role of verapamil in cysteamine-induced duodenal ulcer, further studies would be needed.