J Majka

Jagiellonian University, Cracovia, Lesser Poland Voivodeship, Poland

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Publications (63)278.75 Total impact


  • No preview · Article · Apr 2015 · Gastroenterology
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    ABSTRACT: Hormonal peptides like ghrelin, orexin A (OXA) or nesfatin-1 not only regulate appetite, which is their basic biological function, but also contribute to mechanisms responsible for maintaining integrity of the gastric mucosa. Previous studies including those from our laboratory have revealed that their gastroprotective effect results from cooperation with other factors responsible for protection of the gastric mucosa, including prostaglandin (PG) synthesis pathway, nitric oxide (NO) and the sensory afferent fibres releasing the vasoactive neurotransmitters. The aim of the present study was to determine whether ghrelin, orexin-A (OX-A) or nesfatin-1 with their protective effect on the gastric mucosa, also can modify the healing of chronic gastric ulcers. Furthermore, an attempt was made to explain participation of these peptides in healing processes of chronic gastric ulcers with comorbid conditions for the human beings resulted from diabetes mellitus. In our study, a model of gastric ulcers caused by concentrated acetic acid to induce the chronic gastric ulcers was used, while the clinical condition corresponding to diabetes was induced by single injection of streptozotocin (STZ). We found that ghrelin, OX-A and nesfatin-1 accelerate dynamics of the acetic acid ulcers healing, confirmed by a reduction in the ulcer area and this effect was accompanied by an increase in gastric blood flow at the ulcer margin. Destruction of sensory afferent fibres with capsaicin or blocking of vanilloid receptors with capsazepine resulted in a significant reduction of ghrelin, OX-A and nesfatin-1-induced acceleration of ulcer healing. Similar results were obtained when an NO-synthase blocker, L-NNA was used in a combination with these peptides. Moreover, it was found that OX-A and nesfatin-1 failed to accelerate the healing process under diabetic condition because both these hormones induced reduction in the ulcer area and the increase in blood flow in normal, non-diabetic rats were completely lost in the group of animals with diabetes. Treatment with OX-A and nesfatin-1 increased superoxide dismutase (SOD) mRNA expression even in acetic acid ulcers concurrent with diabetes. However, the treatment with OX-A and nesfatin-1 failed to alter the increase in gastric mucosal mRNA expression for ghrelin and hypoxia-inducible factor 1-alpha (HIF-1α), this latter effect that had been strongly pronounced in diabetic animals. We conclude that the hormonal peptides involved in the regulation of satiety and hunger such as ghrelin, OX-A and nesfatin-1 contribute to the process of chronic gastric ulcers healing cooperating with NO and sensory afferent nerve endings releasing vasoactive neuropeptide CGRP. Furthermore, OX-A and nesfatin-1, the two relatively unrecognized peptides, play an essential role in healing process of chronic gastric ulcers activating the gastric blood flow at ulcer margin and the mucosal regeneration and both ulcer healing and accompanying hyperemia at ulcer margin are greatly impaired during diabetes. Possibly, loss of the healing effect of these peptides during diabetes results from an interaction with radical generation processes as reflected by an increase of mRNA expression for SOD as well as the failure of their attenuating activity on proinflammatory factors such as HIF-1α.
    No preview · Article · Oct 2013 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
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    ABSTRACT: Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake, however very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.5h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5-40μg/kg i.p.) significantly decreased gastric acid secretion and attenuated gastric lesions induced by WRS, and this was accompanied by a significant rise in plasma NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO concentration, generation of PGE2 in the gastric mucosa, an overexpression of mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory cytokine IL-1β and TNF-α mRNAs. Nesfatin-1-induced protection was attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin, and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This study shows for the first time that nesfatin-1 exerts a potent protective action in the stomach of rats exposed to WRS and these effects depend upon decrease in gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the activation of vagal and sensory nerves and vanilloid receptors.
    No preview · Article · Aug 2013 · Peptides

  • No preview · Article · May 2013 · Gastroenterology

  • No preview · Article · May 2012 · Gastroenterology
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    ABSTRACT: Export Date: 20 November 2013, Source: Scopus, doi: 10.5114/pg.2012.33041, Language of Original Document: Polish, Correspondence Address: Brzozowski, T.; Katedra Fizjologii, Uniwersytetu Jagiellońskiego Collegium Medicum, ul. Grzegorzecka 16, 31-531 Kraków, Poland; email: mpbrzozo@cyf-kr.edu.pl, Chemicals/CAS: ghrelin, 304853-26-7; nitric oxide, 10102-43-9; prostaglandin synthase, 39391-18-9, 59763-19-8, 9055-65-6, References: Kanai, Y., Tanuma, S., Purification of a novel B cell growth and differentiation factor associated with lupus syndrome (1992) Immunol Lett, 32, pp. 43-48;
    No preview · Article · Jan 2012 · Przegląd Gastroenterologiczny
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    Full-text · Chapter · Nov 2011

  • No preview · Article · Jan 2011 · Gastroenterology
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    ABSTRACT: Introduction: Development of gastroesophageal reflux disease (GERD) takes place when the balance between irritant and protecting mucous membrane mechanisms is impaired. The chronic inflammation of the oesophagus results in serious complications including Barrett's metaplasia progression into esophageal adenocarcinoma. In the last few years the incidence of chronic gastroesophageal reflux disease has been increasing, especially in highly developed countries, and this chronic disease may result in the development of oesophageal adenocarcinoma, which is also observed with increased frequency. Aim: Creation and comparison of chronic gastroesophageal reflux disease models, as well as estimation of their suitability for the investigation of the process of natural carcinogenesis in the oesophagus. Material and methods: Ninety Wistar rats were used for the study on development of chronic oesophageal inflammation. Three major groups, A - side to side anastomosis, B - side to end anastomosis and C - side to end anastomosis with total gastrectomy, were selected. In each group a different operation technique was performed to induce chronic oesophageal reflux. Groups A and B were characterized by mixed gastroduodenal reflux while group C included animals with only alkaline reflux. Results: In all three experimental models of GERD the morphological changes of the oesophageal mucosa were observed by gross inspection starting 1 month after the surgery. Under microscopic investigation chronic inflammation of the oesophageal mucosa progressing to Barrett's metaplasia and in some cases to cancer was also confirmed. Conclusions: All experimental animal models developed due to GERD are highly reproducible and exhibit low mortality. Macroscopic and microscopic assessment of oesophageal inflammation that developed in response to experimental reflux confirmed that these models are suitable and useful for determination of the pathogenesis of Barrett's related oesophageal cancer.
    No preview · Article · Jan 2011 · Przegląd Gastroenterologiczny
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    ABSTRACT: Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage and inflammation progressing chronic esophagitis and premalignant Barrett's esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in the progression of BE toward adenocarcinoma of the esophagus has not been extensively studied in experimental models of BE in animals and in human subjects. We evaluated the expression of COX-2 in rat model of BE and examined the usefulness of COX-2 expression in determining the risk of malignant transformation in patients with BE treated with argon plasma coagulation (APC) that allows for effective ablation of metaplastic mucosa (group A) without or with proton pump inhibitors (PPI). In addition, the group B of patients was subjected to laparoscopic Nissen's fundoplication and group K that served as control, received PPI treatment only. Expression of COX-2 was evaluated in fresh-frozen biopsy specimens obtained from the distal esophagus in all 60 patients before and 12 months after treatment. In experimental studies, eighty rats were surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was evaluated by macroscopic and histological index score, the plasma IL-1beta and TNF-alpha levels was determined by ELISA and the mucosal expression of COX-2 mRNA and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic esophagitis was developed in all EGDA animals followed by the rise in the plasma TNF-alpha and IL-1beta levels. Histology revealed extensive esophageal ulcerations with development of columnar epithelium, formation of mucus glands in squamous epithelium, intestinal metaplasia distant to anastomosis consisting of goblet cells, infiltration of inflammatory cells including plasma cells and lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control animals but strongly upregulated in metaplastic Barrett's epithelium. In BE patients, the overexpression of COX-2 was documented in patients with dysplasia. After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2 mRNA was markedly reduced and these effects were positively correlated with histopathological findings. Controls failed to show significant alterations in COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of the chronic esophagitis by the gastrointestinal refluxate resembling many features of those observed in human Barrett's esophagus, as confirmed by severe morphology changes, excessive release of proinflammatory cytokines TNF-alpha and IL-1beta and overexpression of COX-2, and 2) the significant correlation of the degree of COX-2 overexpression with histopathological findings indicates the usefulness of this inducible biomarker as a valuable indicator of the risk of malignant transformation in patients with BE.
    Full-text · Article · Aug 2010 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society

  • No preview · Article · May 2010 · Gastroenterology

  • No preview · Article · May 2010 · Gastroenterology
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    G Burnat · J Majka · P C Konturek
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    ABSTRACT: Bile salts play an important pathogenic role in the development of Barrett adenocarcinoma (BA). However, the precise role of different bile salts in this process is still unknown. The aim of the present study was to compare the effects of two different bile salts, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on the expression of COX-2, CDX-2 and DNA repair enzymes (MUTYH, OGG-1) in the Barrett epithelial cancer cells (OE-19). OE-19 cells were incubated with DCAor UDCA(100 microM or 300 microM at pH=7.0) over 24 h. To investigate the involvement of NF kappaB, in separate experiments the cells were incubated with DCA in the presence of proteosome inhibitor (MG-132). Cells cycle and apoptosis were analyzed by FACS analysis. After incubation of OE-19 cells with bile salts, the expression of mRNA of COX-2, DNA repair enzymes (MUTYH, OGG-1) and caudal-related homebox transcription factor CDX-2 were measured by quantitative RT-PCR. OE-19 cell were also transfected with siRNA-RelA (p65) to asses effect of NF kappaB inactivation on COX-2 and CDX2 expression. DCA caused a stronger reduction in cell survival of OE-19 cells than UDCA. In addition, DCA stimulated directly the translocation of NF kappaB p65 (active form) in the nuclei of OE-19 cells. DCA caused stronger than UDCA stimulation of the COX-2 mRNA expression in these cells and this effect was significantly attenuated by the addition of inhibitor of NF kappaB activity (proteosome inhibitor MG-132). siRNA-RelA reduced expression not only of NF kappaB but also expression of COX-2 as well as CDX-2 mRNA. DCA caused stronger downregulation of mRNA for DNA repair enzymes MUTYH and OGG-1 than UDCA. In contrast, UDCA induced stronger CDX-2 mRNA expression than DCA in OE-19 cells. We conclude that bile salts are involved in the carcinogenesis of Barrett adenocarcinoma via inhibition of DNA repair enzymes and induction of COX-2 and this last effect is, at least partly, mediated by NF kappaB. DCA shows carcinogenic potential due to high upregulation of COX-2, CDX-2 and downregulation of DNA repair enzymes.
    Full-text · Article · Apr 2010 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
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    ABSTRACT: Orexigenic peptides are group of endocrine hormones exerting a pleiotropic influence on many physiological functions including regulation of the feeding behaviour and energy expenditure, release of growth hormone (GH) and inotropic effects on the heart. Some of these peptides such as ghrelin, originally identified in the gastric mucosa, has been involved not only in control of food intake and growth hormone release but also exerts the immunomodulatory and anti-inflammatory properties. This review summarizes the recent attempts to prove the concept that orexigenic peptides such as ghrelin, orexin-A and obestatin besides playing an important role in the mechanism of food intake, exhibit a potent gastroprotective action against the formation of acute gastric mucosal injury induced by various ulcerogens. This protective effect depends upon vagal activity and hyperemia mediated by NOS/NO and COX/PG systems and CGRP released from sensory afferent nerves. In addition, the appetite peptides such as ghrelin and orexin-A are implicated in the mechanism of the healing of preexisting gastric ulcers due to an activation of specific GHS-R1a and OX-R1 receptors and PG/COX system.
    No preview · Article · Feb 2010 · Current pharmaceutical design

  • No preview · Article · May 2009 · Gastroenterology
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    ABSTRACT: Barrett's esophagus (BE) is a precancerous condition leading to the development of adenocarcinoma, associated with intestinal metaplasia. Nowadays, the rapid increase in the incidence of esophageal adenocarcinoma (EAC) has been observed worldwide. Despite the surgical treatment and the introduction of new chemotherapy forms, the 5-year period survival is still bad. In this paper, we provide an update on the pathogenesis of BE and EAC based on the interrelationship between prostaglandins (PG), growth factors (GF), GF receptors and peroxisome proliferator-activated receptors (PPARs) in chronic esophagitis, BE, and EAC. We also attempted to overview the involvement of cyclooxygenase (COX) products and pharmacological inhibitors of COX in the process of proliferation, angiogenesis and apoptosis resulting from their interactions with PPARs. Furthermore, the paper presents some experimental animal models of inducing an acute and chronic esophagitis and Barrett's esophagus, which are useful in understanding the pathogenesis of these diseases under clinical settings. Among the potential pathomechanisms, the cellular processes resulting from transactivation GF receptors by other factors such as PG and their biological activity in chronic inflammation and carcinogenesis are emphasized. Finally, we stressed the impact of the naturally occurring anti-oncogenic mechanisms and the recent advances in the innovative therapy against gastrointestinal cancers.
    No preview · Article · Jan 2009 · Gastroenterologia Polska
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    ABSTRACT: Barrett's esophagus (BE) is a precancerous condition that may lead to the development of esophageal adenocarcinoma (EAC). In the last decade, rapid growth in the incidence of BE and EAC has been observed, and gastroesophageal reflux disease (GERD) and obesity are the most frequent coexisting gastrointestinal pathologies reported in persons living in developed countries. The etiologies of BE and EAC are not fully explained, although GERD and obesity seem to be important risk factors leading to chronic esophageal inflammation and, consequently, to dysfunction of the esophagus. Epidemiological studies indicate high correlation between BE and obesity, especially central and visceral. This is a review of the latest literature concerning the involvement of leptin, the major long-term hormonal signal from adipocytes for the hypothalamic regulation of food intake and energy expenditure via the gut-brain axis. The influence of leptin on cell proliferation and apoptosis, inflammation, angiogenesis, and carcinogenesis is discussed. The contributions of growth factors and prostaglandins to the mechanism of leptin's effects on normal and Barrett's esophageal mucosa and in the development of metaplasia and dysplasia are described. Finally, this paper attempts to provide a short overview on obesity as one of the risk factors responsible for GERD, BE, and EAC.
    No preview · Article · Jan 2009 · Gastroenterologia Polska
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    ABSTRACT: Infection by Helicobacter pylori (Hp) has been linked to extradigestive pathologies including ischemic cerebral disease. The aim of our study was to assess the relationship between chronic Hp infection and ischemic stroke risk factors. 80 patients (pts) aged 60-75 years with ischemic stroke confirmed by CT scans (group I) and 80 age- and gender-matched healthy controls (group II) were included into trial. Atherosclerotic plaques from 20 Hp positive pts were obtained at carotid endarterectomy for Hp DNA assessment by PCR. In all groups following parameters were determined; 1) the prevalence of Hp infection using (13)C-Urea Breath Test (UBT), 2) plasma anti-Hp and anti-CagA IgG and interleukin-8 (IL-8), and 3) plasma lipids and fibrinogen. Hp positive pts and controls received one-week anti-Hp therapy and after six months total cholesterol, low-density lipoprotein (LDL)-cholesterol, fibrinogen and IL-8 levels were re-examined. Hp infection was detected by UBT in 83.75% of stroke pts but only in 65% of controls. CagA seropositivity was also significantly higher in stroke pts (57.5%) than in controls (33.75%). Plasma levels of cholesterol, LDL-cholesterol and fibrinogen as well as IL-8 were significantly higher in Hp positive subjects, especially in pts with ischemic stroke. Six months following successful anti-Hp therapy, the plasma levels of total cholesterol, LDL-cholesterol, fibrinogen and IL-8 were significantly lower than those in Hp positive stroke pts and controls. Hp infection represents risk factor of ischemic stoke via an interaction of Hp cytotoxins or cytokines with atherosclerotic plaques in carotic arteries.
    No preview · Article · Nov 2002 · Medical science monitor: international medical journal of experimental and clinical research
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    ABSTRACT: Helicobacter pylori (Hp) is a common pathogen colonizing the a gastric mucosa, but some reports indicated that it may also be found in the oral cavity, which could serve as a reservoir of the bacteria and a source of gastric reinfection. Accordingly, we aimed to study whether the oral cavity, particularly gingival pockets, are colonized by Hp and whether it could be the source of gastric reinfection. We studied 329 patients with dyspeptic symptoms (257 with chronic gastritis, 15 with gastric ulcer, and 57 with duodenal ulcer). The [13C]urea breath test (UBT), gastroscopy, and Hp culture from gastric biopsies were carried out, and material was collected from the oral cavity (gingival pocket) for bacteriological culture and genomic DNA studies. The serum was obtained for anti-Hp IgG and anti-CagA assays and saliva for anti-Hp IgA determination using the ELISA technique. Bacteria in material from gingival pockets and biopsies from the corpus and antrum of stomach of 30 DU patients before and after Hp eradication were also examined by PCR technique, using primers specific for 16S rRNA. All Hp-positive patients (276) were subjected to one week of triple therapy (omeprazole 2 x 20 mg twice a day, clarithromycin 2 x 500 mg twice a day, and metronidazole 2 x 500 mg twice a day). The measurements described above were then repeated at four weeks and six months. Bacteriological culture showed the presence of Hp in the material from oral cavity in about 50% of patients, whereas UBT, used as a gold standard, revealed gastric Hp infection in about 84% of these patients. The eradication was successful in the majority of patients (87%), but about 13% of them were still Hp positive after four weeks and about 21% after six months. Four weeks after Hp therapy, Hp was found in culture from oral samples in 23% (P < 0.05 vs initial) and after six months in 35.1%. The IgA levels recorded in saliva were in a close agreement with UBT results. Hp DNA assessed by PCR in 30 DUs before eradication of Hp was detected in 95% of antral mucosa, 90% in corpus mucosa, and in 35% of gingival pocket material, and after eradication therapy Hp DNA values fell to 25%, 20%, and 10%, respectively. In conclusion, Hp is commonly detected in the oral cavity of patients with dyspeptic symptoms, but the gastric reinfection does not appear to occur in the patients despite oral Hp colonization.
    No preview · Article · May 2002 · Digestive Diseases and Sciences
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    ABSTRACT: Background/Aims: Ulcer healing involves expression of various growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) at the ulcer margin, but the influence of EGF, HGF and bFGF applied locally with or without neutralizing anti-EGF, HGF and bFGF antibodies or cyclooxygenase (COX)-1 and COX-2 inhibitors on ulcer healing and the expression of COX-1 and COX-2 during ulcer healing have only been studied a little. Methods: Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2) received a submucosal injection of either (1) vehicle (saline), (2) EGF, (3) HGF, and (4) bFGF with or without antibodies against EGF, HGF and bFGF or indomethacin (2 mg/kg/day i.p.), a nonspecific inhibitor of COX, or NS-398 (10 mg/kg/day i.g.) and Vioxx (5 mg/kg/day i.g.), both highly specific COX-2 inhibitors. A separate group of animals with chronic gastric fistulas was also used to assess gastric secretion during ulcer healing with and without growth factors. Each growth factor and specific antibody against EGF, HGF and bFGF (100 ng/100 μl each) were injected just around the ulcer immediately after ulcer induction and this local injection was repeated on day 2 following anesthesia and laparotomy. On days 13 and 21, the ulcer area was determined by planimetry, gastric blood flow (GBF) at the ulcer margin was examined by the H2-gas clearance technique, and mucosal generation of PGE2 and the gene expression of COX-1 and COX-2 in the non-ulcerated and ulcerated gastric mucosa were assessed. Gastric ulcers healed progressively within 21 days after induction and this effect was accompanied by a significant increase in GBF at the ulcer margin and in the expression of COX-2 in the ulcer area. Local treatment with EGF, HGF and bFGF produced a significant decrease in gastric acid secretion and significantly accelerated the rate of ulcer healing and raised GBF at the ulcer margin causing further significant upregulation of COX-2 but not COX-1 expression in the ulcerated mucosa. The acceleration of ulcer healing and hyperemia at the ulcer margin exhibited by locally applied EGF, HGF and bFGF were similar to those obtained with systemic administration of these growth factors. HGF applied submucosally, upregulated COX-2 expression and this was significantly attenuated by concurrent treatment with antibody against this peptide. Anti-EGF and anti-bFGF antibodies completely abolished the acceleration of the ulcer healing and hyperemia at the ulcer margin induced by these growth factors. Indomethacin and both COX-2 inhibitors significantly prolonged ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and GBF at the ulcer margin. The acceleration of ulcer healing by EGF, HGF and bFGF and the accompanying rise in GBF at the ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vioxx. Conclusions: (1) Growth factors accelerate ulcer healing due to enhancement in the microcirculation around the ulcer and these effects are specific because they can be abolished by neutralization with antibodies; (2) COX-2-derived prostaglandins and suppression of gastric secretion may play an important role in the acceleration of ulcer healing by various growth factors, and (3) the local effects of EGF, HGF and bFGF on ulcer healing can be reproduced by their systemic application indicating the high efficacy of growth factors to accelerate this healing.
    No preview · Article · Sep 2001 · Digestion

Publication Stats

1k Citations
278.75 Total Impact Points

Institutions

  • 1996-2013
    • Jagiellonian University
      • Department of Physiology
      Cracovia, Lesser Poland Voivodeship, Poland
  • 2012
    • Collegium Medicum of the Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1994-1995
    • Siena Heights University
      Newark, New Jersey, United States
  • 1992-1994
    • Krakow University Hospital
      Cracovia, Lesser Poland Voivodeship, Poland