Biomedical subjects

Z Warzecha

Publications and source records attributed to Z Warzecha.

44 records · Page 3Linked to original sources

PubMed1989

Cholecystokinin receptor antagonism by peptidergic and non-peptidergic agents in rat pancreas.

1. Graded doses of bombesin infused I.V. into conscious rats with chronic pancreatic fistulae induced a dose-dependent stimulation of protein secretion, similar to that obtained with caerulein. This stimulation does not appear to be mediated by cholecystokinin (CCK) receptors because peptidergic (CR-1409) and non-peptidergic (L-364718) CCK antagonists failed to affect protein secretion at a dose range which caused almost complete suppression of caerulein-induced pancreatic secretion. 2. Studies in vitro on isolated rat pancreatic acini revealed that caerulein, pentagastrin and bombesin all showed the same efficacy in their ability to stimulate amylase release. In contrast, CCK antagonists competitively inhibited amylase release induced by caerulein and pentagastrin but not by bombesin or urecholine, indicating that the latter two agents act directly on acinar cells via receptors which are separate from those involved in stimulation induced by caerulein and pentagastrin. 3. DNA synthesis, measured by the incorporation of [3H]thymidine into DNA, was significantly stimulated by caerulein, soybean trypsin inhibitor (FOY 305), pentagastrin and by bombesin in a dose-dependent manner. CCK receptor antagonists prevented stimulation of DNA synthesis induced by caerulein, FOY 305 and pentagastrin but not by bombesin. 4. This study indicates that bombesin strongly stimulates pancreatic enzyme secretion, with an efficacy similar to that of caerulein, and also exerts a potent growth-promoting action on the pancreas, both effects appearing to be mediated by mechanisms independent of the CCK receptors.

Animals↗

PubMed1989

[Influence of pregnancy on the healing of chronic gastric and duodenal ulcers. Role of endogenous epidermal growth factor].

The authors examined the influence of pregnancy on the healing of chronic gastric and duodenal ulcers in connection with pregnancy-induced changes of growth parameters of gastric-duodenal mucosa and changes in the level of endogenic EGF. Besides, the level of EGF was lowered by the resection of submandibular glands (sialadenectomy). Pregnancy caused an increase in the speed of the healing of gastric and duodenal ulcers, this effect being the result of the appearance of hyperplastic changes in the gastric-duodenal mucosa. This hyperplasia was the result of the increase in the level of endogenic EGF. Sialadenectomy decreased the level of EGF in the blood serum preventing total pregnancy hyperplasia of the mucosa in the stomach and partly in the duodenum, which resulted in the total abolition of favourable influence of pregnancy on the healing of gastric ulcers and reduction of the influence of pregnancy on the healing of duodenal ulcers. The results obtained show that the gastric and duodenal mucosa during pregnancy has an increased ability to regenerate, this ability resulting from the hyperplasia of the mucosa taking place in pregnancy, which is the effect of an increase in the level of endogenic EGF.

Chronic Disease↗

PubMed1988

Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats.

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action.

Administration, Oral↗

PubMed1988

Epidermal growth factor (EGF) in the gastroprotective and ulcer healing actions of colloidal bismuth subcitrate (De-Nol) in rats.

Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: role of gastrin and epidermal growth factor.

Growth hormone-releasing factor (GRF) was reported to possess the growth-promoting action on the gastroduodenal mucosa that can be augmented by removal of endogenous somatostatin. Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats. GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA. GRF also significantly increased serum gastrin levels and the tissue contents of epidermal growth factor (EGF) in salivary glands, duodenum and pancreas, suggesting that both gastrin and EGF could contribute to mucosal trophic and ulcer healing effects of GRF. Somatostatin (100 micrograms/kg/day for 7 days) abolished almost completely the ulcer healing and mucosal growth-promoting effects of GRF and this was accompanied by the reduction in serum gastrin level and the tissue contents of EGF suggesting that the suppression of gastrin and EGF release could contribute to the observed effects of somatostatin. We conclude that GRF has both the ulcer healing and the mucosal trophic actions which can be antagonized by somatostatin and that gastrin and EGF may be implicated in these actions.

Acetates↗

PubMed1987

Effect of somatostatin on the growth of gastrointestinal mucosa and pancreas in rats. Role of endogenous gastrin.

This study was undertaken to determine the influence of somatostatin on the growth of gastric, duodenal, and pancreatic tissue in rats placed on liquid diet. In the first part of the study animals were fed an elemental liquid diet for 10 days and then killed, and the growth of the oxyntic gland area of the stomach, 2 cm segments of duodenum and pancreatic tissue was determined. Feeding an elemental diet caused a decrease in organ weight, nucleic acid contents and serum gastrin level. Subsequent addition of pentagastrin prevented this reduction in organ weight and RNA and DNA contents while somatostatin failed to affect the decrease in growth parameters or serum gastrin level in tests with or without addition of pentagastrin. In a second part of the study, sham operated and antrectomised rats were used. Antrectomy caused a significant decrease in serum gastrin concentration and resulted in a significant reduction in the weight and RNA and DNA contents of the tissue tested. As in liquid diet, subsequent administration of pentagastrin prevented the reduction in the growth parameters both in tests with and without somatostatin. These results suggest that somatostatin inhibits the growth of the gastroduodenal mucosa by a mechanism involving, at least in part, the suppression of gastrin release.

Animals↗

PubMed1986

Inhibition of acid formation by epidermal growth factor in the isolated rabbit gastric glands.

The effects of epidermal growth factor (EGF) on basal and stimulated (with histamine, dibutyryl cyclic AMP, and high concentrations of K+) acid formation have been studied in isolated glands from the rabbit gastric mucosa. The changes in the accumulation of [14C]aminopyrine [14C]AP have been used as an indirect measurement of acid production in the glands. Unstimulated gastric glands accumulated [14C]AP indicating the existence of basal acid production in these glands, and EGF caused a small but significant reduction in basal [14C]AP uptake. A similar reduction of basal [14C]AP uptake was observed after exposure to omeprazole but not after ranitidine or prostaglandin E2 (PGE2). Histamine, dibutyryl cyclic AMP and K+ caused a strong and dose-dependent stimulation of acid formation by the glands. EGF, like omeprazole, reduced dose-dependently the [14C]AP accumulation stimulated by both histamine and dibutyryl cyclic AMP, while ranitidine and PGE2 reduced histamine- but not dibutyryl-cyclic-AMP-stimulated accumulation of [14C]AP. In the absence of other external stimuli, an increased K+ concentration enhanced [14C]AP accumulation to levels similar to those produced by histamine and this effect was not changed by EGF, ranitidine or PGE2 but was inhibited by omeprazole. We conclude that EGF interferes with the final steps of acid production between cyclic nucleotides and proton pump of the parietal cells.

Aminopyrine↗

PubMedDate not supplied

Epidermal growth factor protects against pancreatic damage in cerulein-induced pancreatitis.

Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing action. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was induced by subcutaneous infusion of cerulein (10 microg/kg/h) for 5 h. Initially EGF was administrated twice at doses of 1, 5, 10 or 100 microg/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 microg/kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 30%, respectively, as well as a significant increase in pancreatic weight, plasma amylase concentration, plasma interleukin-1beta (IL-1beta) level and the development of the histological signs of pancreatic damage with marked edema, leukocyte infiltration and vacuolization of acinar cells. Treatment with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and significantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1beta were decreased in rats treated with EGF. We conclude that: (1) EGF exerts a protective effect against CIP, and (2) the beneficial activity of EGF in CIP seems to depend on the increase in pancreatic cell proliferation, the reduction in cytokine generation and the attenuation of the fall in PBF.

Acute Disease↗