Peptic Ulcer Disease and its Screening

Evaluation
The intensity of duodenal ulcers is evaluated using  scores from 0-3.
0=no ulcers
1=superficial mucosal erosion
2=deep ulcer usually with transmural necrosis.
3=perforated or penetrated ulcer.

Critical assessment of the method
In view of the development of modern gastric K+/H+-ATPase Inhibitors the predictive value of methods using experimental ulcers in the rat for clinical healing rats in man has been challenged.

GASTRIC PERFUSION IN THE RAT
PRINCIPLE:-The Inhibitors of gastric acid secretion i,e antagonists act by increasing the pH from lower to higher range.

• The acid is produced due to stimulation by the histaminics, Cholinergic drugs etc.
• Thus is antagonized by drugs such as vasopressin, atropine etc. This method is for secondary screening of active agents or for comparing known agents.

Procedure:-
1. Rats are anesthetized with 25% aqueous urethane solution. Body temperatue is stabilized at 30oc
2. The trachea is cannulated
3. Polythene tube (11cms long and 2mm external diameter) is passed in to the lower esophagus .
4. The jugular veins are exposed and cannulated ; one is connected to the Manometer .
5. The abdomen is opened and the pylore duedonal  junction is exposed .
6. A small glass cannula is introduced, through a cut in the duedonum, in to the stomach.
7. stomach is incised about 3cms long beginning as near as the fundus as possible.
8. Clean the stomach and wash with saline.
9. Suture the stomach and abdomen is then closed by two or three interrupted sutures.
10. The suture is then perfused continuously with a dilute solution of warm 0.00025 N NaOH  which enters through the Polyethylene cannula and flows through the Glasss cannula.
11. The fluid emerging from the Pylorus passes over a glass electrode which records the pH continuosly.
12. There is found to be a linear relation between pH and acidity.
13. The rate of perfusion is about 1ml per min.after passing through the unstimulated stomach,the effluent has a pH 6.0-6.5.
14. Drugs are given through one jugular vein,in 0.1 to 0.4ml,followed by 0.1ml saline.for comparison,histamine dihydrogen phosphate is given,which cause the pH to fall from 6.0-4.0.after about 14min.carbachol is also very active.

For assay of inhibitors of gastric acid secretion,antagonists are administered intravenously immediately before,or accompanying the agonist.(e.g.histamine).

• --vasopressin is a standard inhibitor at 120-480 milli units.
• --atropine is also used as inhibitor
• Other methods used for screening.

ISOLATE RAT STOMACH
It was recommended for evaluation of H2 receptor antagonists

ISOLATED GASTRIC MUCOSAL PREPARATION
For studying the pharmacology of gastric secretion and synthesis or release of endogenous substance

PRIMARY CULTURE OF RAT GASTRIC EPITHELIAL CELLS
An in vitro model for evaluation of antisecretory agents using primary cultures of rat gastric epithelial cells.

EVALUATION OF ANTACIDS
The main activity of antacids to reduce the acidity of the gastric content thrrough neutralization and increasing The intragastric pH

Ethanol
Induced mucosal damage in rats(cytoprotective activity) ethanol produces gastric lesions in experimental animals it is inhibited by drugs, such as prostaglandins (Pg’s) have very limited relevance to prediction of ulcer healing potential in humans.

Reference
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