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Experimental production of peptic ulcer, gastric damage and cancer models and their use in pathophysiological studies and pharmacological treatment--Polish achievements.

The common acid related diseases of the upper GI tract could be considered as primarily due to the defect in barrier function either of the gastric mucosal or duodenal epithelium leading to the formation of gastric or duodenal ulcers. An attempt was made in this chapter to discuss the history of peptic ulcer disease in humans and methods for the production of acute gastric lesions and ulcers in experimental animals with the special attention focused to the contribution of Polish scientists and investigators into this field. Early surgical advances in the management of peptic ulcers were emphasized that were then subsequently replaced by pharmacological treatment (histamine H(2)-receptor antagonists, proton pump inhibitors) and considered as the major strategy against the acid disorders. This included the immense body of work performed by numerous group of investigators, including Polish researchers, to identify the effects of acid, bile salts, aspirin and other non-steroidal anti-inflammatory drugs (NSAID), stress, Helicobacter pylori (H. pylori) infection, prostaglandins (PG) and nitric oxide (NO) on the integrity of the gastrointestinal mucosa, which all were discussed in this chapter. The concept of major defensive mechanism in the stomach called "cytoprotection", originally proposed by Andre Robert is recalled in the relevance to the great contribution of Polish scientist working at the Jagiellonian University in Cracow. These experimental studies gave a new insight into the mechanism of action of arachidonate cascade products such as PGs, tromboxanes and leukotrienes and had opened the new therapeutic avenues for the gastroprotective treatment of the acute gastric mucosal damage. Detailed studies revealed, however, that PG-induced cytoprotection offers a short-term protection against gastric lesions induced by corrosive agents but unfortunately this phenomenon gives a little, if any, impact to the process of ulcer healing. The experimental studies on healing of gastric ulcers that become supportive for the clinical trial in humans, performed also by Polish pioneers and the effect of numerous growth factors (EGF, TGF alpha), NO inhibitors, cyclooxygenase- (COX)-1 and COX-2 inhibitors and new safer derivatives of NSAID releasing NO in protection and ulcer healing are discussed. Finally, the major discovery by Warren and Marshall of H. pylori that have been studied world-wide in experimental animals including also Polish investigators, allowed for the better insight to the pathological consequences of this germ infection in the gastric mucosa and helped to establish the anti-H. pylori eradication therapy.

Animals↗

Physical and chemical properties of extracellular staphylococcal lipase.

Highly purified staphylococcal lipase was subjected to physico-chemical analysis. Effect of ionic strength and of protein structure modifying agents supports views suggesting the subunit structure of this enzyme. Chelating and reducing agents, thiol group inhibitors, and bile acid salts do not influence the enzyme activity. Digestion of purified staphylococcal lipase with proteolytic enzymes indicates that lipase is sensitive to trypsin, alpha-chymotrypsin and pronase.

Guanidine↗

Studies on gastrointestinal mucus.

Mucus is secreted throughout the gastrointestinal tract. The primary secretion is the water insoluble gel adherent to the mucosal surface but substantial amounts of mucus also occur in the lumen. The following are discussed: the functions of mucus; the structure and properties of mucus; study of the adherent mucus gel on the mucosal surface; the effects on mucus properties of proteolysis; thiol agents; bile salts; acid and hyperosmolar solutions. Much of our work on mucus has been with that from the stomach but where possible studies on the intestines and colon are discussed. Studies show that mucous secretions from the different regions of the gastrointestinal tract have similar rheological properties although the component glycoproteins differ in their detailed structure.

Animals↗

[Cloning, determination of primary structure, and expression of the C-terminal segment of human cholesterol-esterase/lipase, containing the antigenic determinant of the protein, in Escherichia coli].

Clone pHICE0.9 was selected from human insulinoma cDNA library by immunoscreening with antibodies against total human insulinoma proteins. This clone contains a 0.9 kb cDNA insert and expresses a fusion protein with beta-galactosidase. Nucleotide sequences of 5'- and 3'-terminal regions of this cDNA insert show that clone pHICE0.9 expresses a protein which is identical to the C-terminal fragment (amino acids 483 to 745) of human pancreatic cholesterol esterase and Homo sapiens bile-acid-salt-stimulated lipase from milk. It is concluded that the protein fragment contains the antigenic determinant of human cholesterol esterase/lipase, and can be used for lipase determination in blood.

Amino Acid Sequence↗

Separation of polynuclear aromatic hydrocarbons by micellar electrokinetic capillary chromatography using sodium taurodeoxycholate modified with organic solvents.

The usefulness of a bile acid salt, sodium taurodeoxycholate (STDC), as a surfactant and organic solvents as organic modifiers for the separation of 16 polynuclear aromatic hydrocarbons (PAHs) on the U.S. EPA priority pollutant list by micellar electrokinetic capillary chromatography (MEKC) was investigated. The best resolution of analytes was obtained with a phosphate-borate buffer containing 50 mM STDC and 30% acetone. Short capillaries effected rapid (< 6 min) partial PAH separation, an approach that has potential use in screening studies. The capability of the developed separation system was demonstrated in the analysis of ambient air extracts.

Acetone↗