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Professor Jerzy Kaulbersz, pioneer of Polish gastroenterology

100%

Konturek S. J.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 2

Jerzy Kaulbersz was undoubtedly the father of experimental gastroenterological physiology in Poland. He pioneered the neural and endocrine aspects of the mechanisms controlling gastric and pancreatic secretion by assessing the influence on this secretion of vagal nerves and endocrine factors such as gastrin, enterogastrone, urogastrone, pituitary, adrenal, thyroid and sex hormones as well as bile, hypoxia and X-ray irradiation. He introduced various models of peptic ulcerations such as induced by pylorus-ligation (Shay ulcers) or Mann-Williamson ulcers to test the influence of neuro-endocrine factors on the formation and healing of these ulcerations. This review is designed to commemorate the outstanding contribution to experimental gastroenterology of Professor Kaulbersz, who first studied biology in German universities to obtain the title of Doctor of Natural Philosophy (Ph.D.) in Freiburg in 1913 and then completed medical studies at the Medical Faculty of the Jagiellonian University in Cracow receiving the title of Doctor of Universal Medicine (MD) in 1920. He then joined Department of Physiology of Jagiellonian University in Krakow as its assistant and gradually was appointed docent and finally promoted to professor in this Department, working here as chairman from 1934 to 1964 with only 7 years interruption when he spent the time of world war II in USA, working at various departments of experimental gastroenterology and publishing his outstanding papers in most prestigious physiology journals such as American Journal of Physiology. He possessed comprehensive knowledge of physiology and was gifted to create and organize Cracow Department of Physiology. Moreover he became co-founder of the of Polish Physiological Society, the honorary member of American Physiological Association, honorary member of Polish Society of Gastroenterology and Physiology and received the diploma of Doctor Honoris Causa of Medical Academy in Cracow. This ad memoriam note commemorates his achievements at one hundred twenty anniversary of Prof. Kaulbersz birth with intention to bring his fundamental discoveries to younger physiologists and pharmacologists.

2

Gastric secretion - from Pavlov's NERVISM to Popielski's histamine as direct secretagogue of oxyntic glands

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

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nr 3

43-68

Gastric acid and pepsin secretions result from the interplay of neurohormonal factors with stimulatory and inhibitory actions on oxyntic glands. At the turn of XIX century, the notion of nervism or entire neural control of digestive functions, developed by Pavlov prevailed. However, in the second part of XX century, hormonal control has been thought to play a major role in the mechanism of gastric secretion, especially gastrin, which was isolated and synthesized in 1964 by Gregory. Polish traces in gastroenterological history started with the discovery of histamine, a non-nervous and non-gastrin compound in oxyntic mucosa by L. Popielski in 1916, who found that this amine is the most potent and direct stimulant of gastric acid secretion. This histamine concept was supported by leading American gastroenterologists such as A.C. Ivy, championed later by C.F. Code, and clinically applied for testing gastric secretion by K. Kowalewski. Recently, it received a strong support from pharmacological research when J. Black designed H2-receptors antagonists, which were first discovered by M.I. Grossman and S.J. Konturek to inhibit not only histamine-, but also meal- and vagally-induced gastric acid secretion, thus reinforcing the notion of the crucial significance of histamine in the control of gastric secretion as the final common chemostimulator. In conclusion, Polish traces appear to be substantial in gastric history due: 1) to discovery by Popielski that histamine is a major, direct stimulus of gastric secretion; 2) to clinical application of this agent by Kowalewski in testing maximal gastric secretory activity; and 3) to clinical use of histamine H2-antagonists in control of gastric acid secretion and treatment of peptic ulcers.

3

Physiology of pancreatic secretion

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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1998

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tom 49

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nr 2

4

Progress in H.pylori related basic and clinical research in Poland

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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1997

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tom 48

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nr 1

5

New aspects of clinical pharmacology of antacids

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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1993

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tom 44

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nr 1

6

Brain-gut axis; historical background and present development

100%

Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2001

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tom 52

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nr 2

7

Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik

Role of leukotrienes and platelet activating factor in gastric mucosal damage and repair

64%

Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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1991

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tom 42

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nr 2

Gastric mucosal integrity depends upon the balance between „aggressive” factors and „defensive” mechanisms. The formation of mucosal lesions results from the disruption of defense lines, including the breaking of unstirred mucus layer, the reduction of surface hydrophobicity, extensive exfoliation of surface epithelium, penetration of offending agents deeply into the mucosa and damage to the microvessels. The release of proinflam- matory and vasoactive mediators such as leukotrienes (LT), thromboxanes, platelet activating factor (PAP), endothelins and others has been thought to be involved in the pathomechanism of mucosal injury, especially damage to the micro vascular endothelium, increased vascular permeability, reduction in mucosal blood flow, vascular stasis, tissue ischemia and glandular cell necrosis. This paper reviews the mechanisms and possible pathogenetic implication of two related compounds, LT and PAP in acute mucosal injury by topical irritants such as ethanol, aspirin, bile salts and by stress. LT and PAP arise from similar membrane phospholipids and may regulate the biosynthesis of one another in the damaged mucosa. Although pharmacological studies have clearly demonstrated the noxious effects of cysteinyl LT and PAP on the mucosa, especially when exposed to topical irritants, recent publications have challenged the primary role of these mediators in the pathogenesis of mucosal lesions and ulcerations because the treatment with agents that selectively antagonize their biosynthesis or the receptor sites at the target cells did not always interrupt the chain of events leading to mucosal injury. The role of these mediators in the mucosal repair processes has been little studied but both cysteinyl LT and PAP seem to delay the restitution and healing of the mucosa. Further studies are necessary to clarify to what extent the biosynthesis of LT and PAP and the pharmacological inhibition of their action on the target tissues is related to noxious, protective and reparative events in the mucosa exposed to mild irritants and ulcerogens.

8

The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system

64%

Konturek P. C., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

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nr 3

83-98

At the turn of XIX and XX century, the principal concept explaining the mechanism of secretory activity of the digestive glands was nervism proposed by I. P. Pavlov at Russian physiological school in St Petersburg, and this dogma was widely recognized for several years in other countries. The discovery of secretin in 1902 by W.B. Bayliss and E.H. Starling, and then of gastrin in 1906 by J.S. Edkins, emphasized the hormonal regulation of pancreatic and gastric secretion, respectively. In 1943, A.C. Ivy and E. Olberg discovered a hormone, which contracts the gallbladder - cholecystokinin (CCK), while A. Harper and H.S. Raper described another hormone, pancreozymin, which stimulated pancreatic enzymes. It required over twenty years, however, for these and many other hormones to be identified, purified and synthesized due to the extensive work of several teams including R. Gregory, G. Dockray and Kenner of the UK; J. Rehfeld of Denmark and E. Wunsch of Germany for their work on gastrin; E. Jorpes and V. Mutt of Sweden and N. Yahaihara of Japan for their work on secretin and other GI hormones including, CCK, vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP), motilin, gastrin-releasing peptide (GRP) and others peptides. CCK and pancreaozymin were found by E. Jorpes and V. Mutt to represent structurally a common messenger for pancreatico-biliary secretion. This rapid development of GI endocrinology in the 1960s and 1970s could be attributed to the application of peptide biochemistry in characterizing various peptide hormones. The technique of radioimmunoassay by S.A. Berson and R.S. Yalow in 1959 measured minute amounts of hormones in the circulation and tissue, and the technique of immunocytochemistry detected the cellular origin of these hormones. Further progress in molecular biology led to sequencing GI hormones and their prohormones, and opened a new area of investigation for the physiological role of these hormones in the mechanism of digestive gland secretion, motility of gastrointestinal tract, visceral blood flow, tissue growth and integrity in health, as well as in various digestive diseases. Overall, apparent divergent concepts, the nervous control (Pavlov) and hormonal control (Bayliss and Starling), greatly facilitated the elucidation of the interacting neuro-hormones during the cephalic, gastric, and intestinal phases of gastric and pancreatic secretion in health and digestive diseases. Although Polish contributions in the early phase of GI endocrinology concerned mostly gastric inhibitory hormones such as enterogastrone and urogastrone, major Polish traces can be detected in the elucidation of origin and physiological role and pathological involvement of gastrin, CCK, secretin, motilin, gastric inhibitory peptide and the most recent additions of enterohormones such as epidermal growth factor, somatostatin, leptin or ghrelin. Major achievements have been obtained in gastric and colorectal cancerogenesis involving gastrin and its precursor, progastrin.

9

Gastric analysis with fractional test meals [ethanol, caffeine, and peptone meal], augmented histamine or pentagastrin tests, and gastric pH recording

64%

Kwiecien S., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2003

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tom 54

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nr 3

69-82

For centuries it was recognized that the stomach produces a juice, which has acidic properties, however, it was not until 1824 when Prout demonstrated the presence of hydrochloric acid in gastric juice. At the same time experiments on a patient with gastric fistula began by W. Beaumont showing alterations of acid secretion after meals and under various psychological conditions. After the discovery by L. Popielski in 1920 that histamine is a direct stimulant of oxyntic glands, histamine started to be used in the 1930s in gastric secretory tests. Then in 1949 the dose of histamine was established by K. Kowalewski to induce in humans maximal gastric secretion and in 1953 Kay from UK, using a similar dose of histamine (0.04 mg/kg), introduced augmented histamine test to determine maximal acid output. The digestive period of gastric secretion can be divided into 3 phases: cephalic phase, gastric phase, and intestinal phase. When an acidified meal reaches the antrum or proximal part of the small intestine, the inhibitory autoregulatory mechanisms are triggered. Using a peptone meal as a physiological stimulant of gastric secretion, Fordtran and Walsh designed in 1973 the intragastric titration method. Histamine stimulates H1 and H2 receptors, producing some side effects so Betazole (Histalog), an analogue of histamine was introduced, because of smaller side effects than with histamine. In 1967, pentagastrin, which contains a C-terminal amino-acid sequence of gastrin and does not exert serious side effects, was applied first in Poland as a stimulant of gastric acid secretion instead of histamine. At the present time, a 12 or 24 h pH-metry with a magnetic recording of gastric acidity using the Digitrapper was found to have a greater diagnostic value in assessment of gastric acid secretion under natural conditions including meal than classic gastric secretory tests. This technique has been widely used in detecting the duodeno-gastric or gastro-esophageal reflux (GERD) and testing various drugs affecting gastric acid secretion and healing acid-pepsin disorders.

10

Melatonin and aging: prospects for human treatment

64%

Bubenik G. A., Konturek S. J.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 1

Human life span, with or without modern medicine is around 85-95 years. All living creatures have their inner clock that measures their daily (circadian) and their seasonal (circannual) time. These time changes are mediated by the alteration of levels of melatonin, an evolutionary ancient hormone, which is produced in many body tissues, including the pineal gland, retina and the gastrointestinal tract (GIT). Light is blocking the production of melatonin in the pineal gland, darkness is stimulating it. So, the diurnal changes of light intensity of melatonin, provide a "daily clock" and the seasonal changes provide a "seasonal clock". Finally, the reduction of melatonin observed with aging, may indicate the presence of an "age clock". Melatonin is a strong antioxidant (often it is called scavenger of free radicals), which protects the body from the effects of noxious compounds. Therefore it was hypothesized that the reduction of melatonin levels with age contributes to the aging process. So far, the only remedy to extend the life span was a 40% reduction in caloric intake, which prolonged the life in mice, rats, dogs and monkeys by 30-50%. A large group of people imitate these experiments performed on animals, but the results of these experiments will not be known for several decades. How is being hungry prolonging the life span? There is a connection between caloric reduction and melatonin levels in GIT. Several experiments indicate that fasting in animals substantially increased their production of GIT melatonin. Therefore, instead of being permanently hungry, a prolongation of human life could be achieved by a replacement melatonin therapy. A daily intake of melatonin before bed time might achieve the same effect as fasting e.g. an increase of body melatonin levels, which will protect the individual from the ravages of old age. That includes Parkinson's disease and Alzheimer's disease. There is a large group of people taking melatonin daily who believe that melatonin is the "fountain of youth". Those are the subjects which will one day provide an experimental evidence of the efficacy of melatonin.

11

Effects of prostaglandin of E, F and I series, leukotriene C4 and platelet activating factor on amylase release from isolated rat pancreatic acini

64%

Jaworek J., Konturek S. J.

Journal of Physiology and Pharmacology

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1993

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tom 44

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nr 4

12

New approach to 13C-urea breath test: capsule - based modification with low-dose of 13C-urea in the diagnosis of Helicobacter pylori infection

64%

Bielanski W., Konturek S. J.

Journal of Physiology and Pharmacology

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1996

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tom 47

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nr 3

13

Role of nitric oxide in gastroduodenal alkaline secretion

64%

Bilski J., Konturek S. J.

Journal of Physiology and Pharmacology

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1994

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tom 45

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nr 4

14

Role of Helicobacter pylori infection in gastro-duodenal secretion and in pathogenesis of peptic ulcer and gastritis

64%

Konturek P.Ch., Konturek S. J.

Journal of Physiology and Pharmacology

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1994

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tom 45

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nr 3

15

Effect of 16, 16-Dimethyl prostaglandin E2 methyl ester on gastric secretion induced by pentagastrin and pepton meal in man

51%

Swierczek J., Kwiecien N., Oleksy J., Konturek S. J.

Acta Physiologica Polonica

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1976

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tom 27

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nr 2

16

Helicobacter pylori infection in gastric cancerogenesis

51%

Konturek P. C., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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2009

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tom 60

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nr 3

3-21

Gastric cancer (GS) remains one of the most common cancers worldwide. It is considered as the second most frequent cause of cancer death worldwide, although much geographical variation in incidence exists. Many studies before linked Helicobacter pylori (Hp) which is now considered as an important pathogen, to the risk of developing noncardia GS. This overview attempts to summarize the recent basic and clinical evidence on the link between H. pylori and gastric cancer, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of Hp and the investigation of their relevance to peptic ulcer disease. It become evident that Hp eradication by antibiotic treatment combined with proton pump inhibitor (PPI) serves as the primary chemoprevention strategy to reduce gastric cancer incidence. Moreover, the eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. Due to understanding the molecular nature of GC which has been nowadays under intense investigation, our review attempts to highlight recent progress in the field of research on Hp-induced GS. We discuss the geographical diversity in Hp infection and cancer incidence and the mechanistic role of gastrin, cyclooxygenase-2 (COX-2), growth factor, nitric oxide (NO)/NO synthase and E-cadherin/beta-cathenin systems, apoptosis and angiogenesis in Hp-induced gastric carcinogenesis. In addition host-related genetic susceptibility and the role of overexpression of a proinflammatory cytokines and their polymorphism is discussed in the relation to the cascade of events such as gastric atrophy, intestinal metaplasia and dysplasia that finally lead to adenocarcinoma.

17

Gastric cancer and Helicobacter pylori infection

51%

Konturek P. C., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

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2006

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tom 57

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nr 3

51-65

The Nobel prize in Physiology and Medicine in 2005 was presented to Barry Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but only the involvement of this germ in gastritis and peptic ulcer has been mentioned in the award sentence, while numerous epidemiological, clinical and experimental studies and reports emphasized the crucial role of Hp in pathogenesis of gastric cancer (GC). This review is based on the old concept proposed by P. Correa much before the discovery of spiral bacteria in the stomach, postulating the cascade of mucosal changes from acute/chronic gastritis into the atrophic gastritis with intestinal metaplasia and finally to dysplasia and GC. It is now widely accepted view that Hp infection is the major initiator of the inflammatory and atrophic changes in gastric mucosa accompanied by an over-expression of certain growth factors such as gastrin as well as of cyclooxygenase-2 (COX-2) and anti-apoptotic proteins including survivin and B-cl2, leading to proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of apoptosis and formation of gastric tumour. All the morphological and biochemical changes associated with the transformation of mucosal cells into the cancer cells can be traced in excellent experimental model of gastric cancerogenesis induced by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved in several prospective clinical trials to greatly reduce the incidence of GC and this was confirmed on the gerbil model of Hp-induced GC, it has been postulated; a) that Hp is the major causal factor in pathogenesis of GC and b) that the only rational approach in attempt to reduce the occurrence of GC is the global eradication of Hp.

18

Nowe metody wytwarzania przewlekłej przetoki trzustkowej u kotów

51%

Konturek S. J., Dubiel J., Gabrys B.

Acta Physiologica Polonica

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1970

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tom 21

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nr 4

19

Intravenous amino acids in the stimulation of gastric secretion

51%

Cieszkowski M., Tasler J., Konturek S. J.

Acta Physiologica Polonica

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1979

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tom 30

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nr 1

20

Prostaglandins and ulcer healing

51%

Konturek S. J., Konturek P. C., Brzozowski T.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 5

5-31

Exogenous prostaglandins (PG) applied in small gastroprotective doses fail to affect healing of gastro-duodenal ulcers but accelerate the healing when used in larger gastric inhibitory doses that appear to enhance COX-2 expression and PGE2 generation in the ulcer area. COX-1 and COX-inhibitors delay ulcer healing, particularly when both COX isoforms are suppressed such e.g. by indomethacin. Dexamethasone, that decreases the expression of COX-2 and mucosal generation of PGE2, delays ulcer healing that can be reversed by the addition of small dose of exogenous PGE2. Proton pump inhibitors (PPI) such as omeprazole and PGE analogs, accelerate ulcer healing mainly due to potent inhibition of gastric acid secretion, but they also augment the COX-2 expression and enzyme activity in the ulcerated mucosa. Endogenous PG generated at ulcer margin appear to be involved in ulcer healing promoted by growth factors and gut hormones such as gastrin or CCK and melatonin acting, at least in part, through increase of induction of COX-2 and local release of PGE2 in the ulcer area . The ulcer healing activity of growth factors (e.g. EGF, TGFalpha, HGF) and certain gut hormones (gastrin, CCK) as well as melatonin, can be attenuated by treatment with COX-1 or COX-2 inhibitors which suppress the release of PGE2 but enhance the expression of COX-2. It is concluded that endogenous PG originating mainly from upregulated COX-2 at the ulcer margin play crucial role in ulcer healing by exogenous PG, PPI, growth factors, gut hormones and melatonin, while COX-1 and COX-2 inhibitors delay ulcer healing by suppressing PG generation, and increasing COX-2 expression in the ulcer area.

Ograniczanie wyników

Professor Jerzy Kaulbersz, pioneer of Polish gastroenterology

Gastric secretion - from Pavlov's NERVISM to Popielski's histamine as direct secretagogue of oxyntic glands

Physiology of pancreatic secretion

Progress in H.pylori related basic and clinical research in Poland

New aspects of clinical pharmacology of antacids

Brain-gut axis; historical background and present development

Role of leukotrienes and platelet activating factor in gastric mucosal damage and repair

The history of gastrointestinal hormones and the Polish contribution to elucidation of their biology and relation to nervous system

Gastric analysis with fractional test meals [ethanol, caffeine, and peptone meal], augmented histamine or pentagastrin tests, and gastric pH recording

Melatonin and aging: prospects for human treatment

Effects of prostaglandin of E, F and I series, leukotriene C4 and platelet activating factor on amylase release from isolated rat pancreatic acini

New approach to 13C-urea breath test: capsule - based modification with low-dose of 13C-urea in the diagnosis of Helicobacter pylori infection