Marek Cieszkowski

EFFECT OF GROWTH HORMONE RELEASE-INHIBITING HORMONE ON GASTRIC SECRETION, MUCOSAL BLOOD FLOW, AND SERUM GASTRIN

In dogs with gastric fistulae and Heidenhain pouches (HP) growth hormone release-inhibiting hormone (GH-RIH) infused intravenously in a dose of 2.5 mug per kg per hr inhibited almost completely acid and pepsin responses to pentagastrin, Urecholine, and a peptone. Histamine-induced acid secretion was more resistant to the inhibition by GH-RIH, and only acid secretion evoked by the lower doses of histamine was suppressed by this peptide. The inhibition of pentagastrin-induced gastric secretion was associated with a marked reduction in mucosal blood flow. The ratio of aminopyrine concentration in the gastric juice and blood plasma was not significantly changed by GH-RIH, indicating that the reduction in mucosal blood flow was secondary to an inhibition of gastric secretion. Gastric acid and serum gastrin responses to a peptone meal adjusted to pH 5.0 and kept in the main stomach at this same pH by intragastric titration were significantly decreased by GH-RIH, indicating that the observed acid inhibition could be attributed at least in part to the suppression of gastrin release. GH-RIH inhibited acid secretion from HP stimulated by liver extract in HP. The finding that GH-RIH inhibits gastric secretion induced by exogenous stimulants as well as by the direct chemical stimulation of the HP mucosa without changing serum gastrin level suggests that the major action of GH-RIH is a direct suppression of the oxyntic glands.

Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow

BACKGROUND Endogenous nitric oxide has been implicated in the control of mesenteric circulation, but its role in the control of pancreatic blood flow and exocrine pancreatic secretion has not been studied. METHODS Secretory studies were performed on conscious dogs with chronic pancreatic fistulas, and changes in pancreatic blood flow were measured by laser Doppler flowmetry in anesthetized animals. RESULTS Infusion of NG-nitro-L-arginine did not affect basal pancreatic protein secretion but suppressed an increase of this secretion induced by L-arginine but not that induced by glyceryl trinitrate. Sham-feeding, meal feeding, and infusion of secretin plus cholecystokinin induced pancreatic protein outputs reaching, respectively, 30%, 74%, and 50% of cerulein maximum in these dogs. Infusion of NG-nitro-L-arginine caused a profound inhibition of these secretions, whereas the addition of L-arginine reversed this inhibition in part. NG-nitro-L-arginine or L-arginine added to the incubation medium of isolated canine pancreatic acini did not affect basal or cholecystokinin-induced amylase release. In anesthetized dogs, infusion of NG-nitro-L-arginine caused a significant reduction in the pancreatic blood flow both while resting and following stimulation with secretin plus cholecystokinin but did not affect this flow in animals treated with glyceryl trinitrate. Addition of L-arginine attenuated the decrease in pancreatic blood flow and the increase in systemic blood pressure caused by NG-L-nitro-arginine. CONCLUSIONS Endogenous NO affects pancreatic secretion probably through the changes in the vascular bed.

The Northern Carpathians plate tectonic evolutionary stages and origin of olistoliths and olistostromes

The olistostromes formed in Northern Carpathians during the different stages of the development of flysch basins, from rift trough post-rift, orogenic to postorogenic stage. They are known from the Cretaceous, Paleocene, Eocene, Oligocene and Early Miocene flysch deposits of main tectonic units. Those units are the Skole, Subsilesian, Silesian, Dukla and Magura nappes as well as the Pieniny Klippen Belt suture zone. The oldest olistoliths in the Northern Carpathians represent the Late Jurassic-Early Cretaceous rifting and post-rifting stage of the Northern Carpathians and origin of the proto-Silesian basin. They are known from the Upper Jurassic as well as Upper Jurassic-Lower Cretaceous formations. In the southern part of the Polish Northern Carpathians as well as in the adjacent part of Slovakia, the olistoliths are known in the Cretaceous- Paleocene flysch deposits of the Pieniny Klippen Belt Zlatne Unit and in Magura Nappe marking the second stage of the plate tectonic evolution - an early stage of the development of the accretionary prism. The most spectacular olistostromes have been found in the vicinity of Haligovce village in the Pieniny Klippen Belt and in Jaworki village in the border zone between the Magura Nappe and the Pieniny Klippen Belt. Olistoliths that originated during the second stage of the plate tectonic evolution occur also in the northern part of the Polish Carpathians, in the various Upper Cretaceous-Early Miocene flysch deposits within the Magura, Fore-Magura, Dukla, Silesian and Subsilesian nappes. The Fore-Magura and Silesian ridges were destroyed totally and are only interpreted from olistoliths and exotic pebbles in the Outer Carpathian flysch. Their destruction is related to the advance of the accretionary prism. This prism has obliquely overridden the ridges leading to the origin of the Menilite-Krosno basin. In the final, postcollisional stage of the Northern Carpathian plate tectonic development, some olistoliths were deposited within the late Early Miocene molasse. These are known mainly from the subsurface sequences reached by numerous bore-holes in the western part of the Polish Carpathians as well as from outcrops in Poland and the Czech Republic. The largest olistoliths (kilometers in size bodies of shallow-water rocks of Late Jurassic-Early Cretaceous age) are known from the Moravia region. The largest olistoliths in Poland were found in the vicinity of Andrychów and are known as Andrychów Klippen. The olistostromes bear witness to the processes of the destruction of the Northern Carpathian ridges. The ridge basement rocks, their Mesozoic platform cover, Paleogene deposits of the slope as well as older Cretaceous flysch deposits partly folded and thrust within the prism slid northward toward the basin, forming the olistostromes.

Comparison of Telenzepine, Pirenzepine and Atropine on Gastric Acid and Pepsin Secretion in Response to Histamine, Pentagastrin, Bethanechol, Sham-Feeding and Feeding

This study was designed to compare gastric antisecretory effects of telenzepine, a new antimuscarinic agent, with those of pirenzepine and atropine in dogs. None of these antimuscarinics affected gastric acid secretion induced by histamine but all of them caused a dose-dependent inhibition of acid secretion from the gastric fistula (GF) and Heidenhain pouches (HP) stimulated by pentagastrin and bethanechol, telenzepine being 5-9 times more potent than pirenzepine and equipotent with atropine. All antimuscarinics were also effective inhibitors of acid responses to sham feeding and ordinary feeding. The inhibitory effect of telenzepine and pirenzepine were not accompanied by any major alterations in plasma gastrin or somatostatin but those of atropine were related to significant increase in plasma gastrin and to significant decrease in plasma somatostatin levels, suggesting the involvement of M2 receptors in the cholinergic control of these hormones. All three antimuscarinics were effective inhibitors of pepsin secretion induced both from the GF and HP by all secretagogues used. Neither telenzepine nor pirenzepine administered in various doses affected the heart rate while atropine caused a significant increase in heart rate confirming that the former agents are selective M1 receptor antagonists. This study provides evidence that telenzepine is more potent than pirenzepine in the inhibition of gastric secretion induced by pentagastrin, bethanechol, sham-feeding and ordinary feeding and that, unlike atropine, it does not increase plasma gastrin responses to meat feeding. In fact, telenzepine and pirenzepine alike reduced plasma gastrin concentrations under these conditions. No influence of these antimuscarinics on plasma somatostatin levels was observed.

Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs

Nitric oxide (NO) was shown to mediate gastric hyperemia following secretory stimulation but its role in the control of gastric secretion has not been clarified. Secretory studies were carried out on conscious dogs with chronic gastric fistula, Heidenhain pouch and esophageal fistula, while changes in gastric blood flow were measured in the mucosa of Heidenhain pouuch by laser Doppler flowmetry. Plasma gastrin was determined by radioimmunoassay. Infusion of NG-nitro-L-arginine (L-NNA) (bolus i.v. injection of 2.5 mg/kg followed by infusion of 0.5 mg/kg/h), a potent inhibitor of nitric oxide synthase, failed to affect basal gastric secretion or plasma gastrin level but suppressed an increase of this secretion induced by sham-feeding, ordinary meat feeding or i.v. infusion of bombesin (0.5 microgram/kg/h), pentagastrin (4 micrograms/kg/h) or histamine (40 micrograms/kg/h). In tests with feeding and bombesin infusion, L-NNA caused a significant and dose-dependent reduction in plasma gastrin levels. The inhibition by L-NNA of gastric acid secretory response to pentagastrin, histamine or feeding was accompanied by a decline in blood flow. Addition of L-arginine (bolus i.v. dose of 50 mg/kg followed by infusion of 5 mg/kg/h) significantly attenuated the L-NNA induced inhibition of gastric secretion and the reduction in plasma gastrin response as well as in the fall of gastric blood flow. We conclude that endogenous nitric oxide affects the gastric secretion and that this effect is mediated, at least in part, by the changes in the gastrin release and gastric blood flow.

COMPARISON OF AMINO ACIDS BATHING THE OXYNTIC GLAND AREA IN THE STIMULATION OF GASTRIC SECRETION

This study was undertaken to compare the ability of L- and D-isomers of amino acids bathing the oxyntic gland area to stimulate acid secretion in conscious dogs with Heidenhain pouch (HP), gastric fistula (GF) and pancreatic fistula (PF). Acid outputs from HP were determined by an intragastric titration method when amino acid solutions were perfused into HP at various concentrations, pH values, and distention pressures. Only L-isomers of all natural amino acids were found to stimulate acid secretion, whereas D-isomers of amino acids tested were completely inert in this respect. The comparison of the secretagogue activity of amino acids shows that L-histidine among essential amino acids and glycine among nonessential amino acids exhibited the strongest stimulation of acid outputs, reaching, respectively, 52 and 40% of the maximal response to histamine. Decreasing the pH of L-histidine solution perfused into HP in sequential order from 5.0 to 1.0 resulted in a stepwise reduction of acid output, falling at pH 1.0 to about 40% of the peak response achieved at pH 5.0. Local irrigation of HP by 2% xylocaine and intravenous infusion of atropine (100 mug per kg per hr) or metiamide (2.9 mg per kg per hr) reduced but did not abolish HP response to chemical stimulation and the pH dependency of this response. We conclude that only L- and not D-isomers of amino acids bathing the oxyntic gland area stimulate acid secretion by a local, gastrin-independent mechanism sensitive to distention pressure and pH.

Effects of Cyclic Hexapeptide Analog of Somatostatin on Pancreatic Secretion in Dogs

Abstract The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 μg/kg or given iv at a dose of 0.5 μg/kg-hr, resulted in a similar inhibition of pancreatic secretion induced by feeding a meat meal, sham-feeding, duodenal acidification, or infusion of secretin or CCK. The inhibition of pancreatic secretion by cyclo-SS was due in part to direct inhibitory action on the exocrine pancreas as well as to the suppression of the release of secretin, insulin, and pancreatic polypeptide. It is concluded that cyclo-SS is a more potent inhibitor of pancreatic secretion than SS-14 and that it is active when administered both parenterally and intraduodenally.

Olistostromes of the Pieniny Klippen Belt, Northern Carpathians

The olistostromes form two belts within the Pieniny Klippen Belt (PKB) in the Northern Carpathians. They mark an early stage of the development of the accretionary prism. The first belt was formed during Late Cretaceous time as a result of subduction of the southern part of the Alpine Tethys. The fore-arc basin originated along this subduction zone, with synorogenic flysch deposits. Huge olistoliths deposited within the Cretaceous–Palaeogene flysch of the Zlatne Basin, presently located in the vicinity of the Haligovce village (eastern Slovakia), provide a good example of the fore-arc olistostrome setting. The second belt is related to the movement of the accretionary prism, which overrode the Czorsztyn Ridge during Late Cretaceous–Paleocene time. The destruction of this ridge led to the formation of submarine slumps and olistoliths along the southern margin of the Magura Basin. The Upper Cretaceous – Paleocene flysch sequences of the Magura Basin constitute the matrix of olistostromes. The large Homole block in the Jaworki village represents the best example of the Magura Basin olistolith. Numerous examples of olistoliths were documented in western Slovakia, Poland, eastern Slovakia and Ukraine. The olistostromes formed within the Zlatne and Magura basins orginated during the tectonic process, forming the olistostrome belts along the strike of the PKB structure.

Tectonics of the western part of the Polish Outer Carpathians

The western part of the Polish Outer Carpathians is built up from the thrust, imbricated Upper Jurassic-Neogene flysch deposits. The following Outer Carpathian nappes have been distinguished: Magura Nappe, Fore-Magura group of nappes, Silesian, Subsilesian and Skole nappes. Interpretation of seismic and magnetotelluric survey from the region South of Wadowice, allows observation of relationship between basement and flysch nappes in the Outer Carpathians. It also allows identification of dislocation cutting both flysch nappes and their basement. All the Outer Carpathian nappes are thrust over the southern part of the North European Platform. The platform basement is composed of older Precambrian metamorphic rocks belonging to the Bruno-Vistulicum terrane. Sedimentary cover consists of Paleozoic, Mesozoic and Neogene sequences. The characteristic features of this boundary are horsts and troughs of general direction NW-SE, turning W-E. Faults cutting only the consolidated basement and the Paleozoic cover were formed during the Hercynian Orogeny in the Carboniferous and the Early Permian. Most of the older normal faults were covered by allochtonous flysch nappes forming thus the blind faults. During the last stage of the geodynamic development the Carpathians thrust sheets moved towards their present position. Displacement of the Carpathians northwards is related to development of dextral strike-slip faults of N—S direction. The orientation of this strike-slip fault zones zone more or less coincides with the surface position of the major faults perpendicular to the strike of the Outer Carpathian thrustsheets. The huge fault cuts formations from the Paleozoic basement through the flysch allochton between the boreholes in Sucha Beskidzka area. The displacement of nappes of the Carpathian overthrust and diapiric extrusion of plastic formations of the lower flysch units occurred along this fault.

Mechanisms of the Inhibitory Action of Prostaglandins on Meal-Induced Gastric Secretion

In dogs with gastric fistula and Heidenhain pouch (HP), 15(S)-15-methyl prostaglandin E2 methyl ester (PG-S) infused intravenously in graded doses (0.5--2.0 microgram/kg/h) inhibited dose-dependently, meal-induced acid secretion both from the vagally innervated main stomach and from the HP. This inhibition was associated with a marked reduction in mucosal blood flow but without significant change in the ratio of aminopyrine concentration in the gastric juice and blood plasma, indicating that the reduction in gastric microcirculation was probably secondary to the inhibition of gastric secretion. In dogs with special cannulae that allowed complete separation of the stomach and the intestine, PG-S caused stronger inhibition of gastric acid and serum gastrin responses to gastric and intestinal meals after application directly to the gastric mucosa, than following duodenal administration. PG-S applied topically to the HP mucosa also suppressed direct chemical stimulation of the HP by L-histidine meal. We conclude that PG-S exerts its inhibitory action on gastric secretion both by local contact with the mucosa via suppression on gastrin release from the antral G-cells and by direct inhibition of the secretory activity of the oxyntic glands.