A sample of colorectal carcinoma is obtained by laser microdissection from a histological preparation of gut epithelium.
Our research is focused on biology, physiology and pathophysiology of the intestine and cellular and molecular mechanisms of corticosteroid regulations. To achieve the aims, our group utilizes wide range of experimental approaches including biochemical analysis (i.e. determination of enzyme activities), genomic and proteomic techniques, microanatomy (laser microdissection) and electrophysiologic techniques (voltage clamp). To elucidate the mechanisms operating under normal and pathological conditions we use specific rat strains with weak and strong HPA axis activity (Fisher 344 and Lewis rats), germ-free animals and animal models of colitis, arthritis and colitis-associated colorectal cancer. Ongoing research topics in our group focus on the elucidation of:
- Effect of psychosocial stress on HPA axis regulation
- Effect of inflammation on local metabolism of glucocorticoids in neuroendocrine regulatory pathways and secondary lymphoid organs
- Role of internal time-keeping system in pathogenesis of colorectal cancer associated with inflammatory bowel disease
- Effect of gut microbiota on neuroendocrine regulatory pathways during stress
- Regulation of intestinal transport
Projects
Stress, a widespread condition of modern society, activates the hypothalamus-pituitary-adrenal (HPA) axis, which results in upregulation of plasma level of glucocorticoid hormones (cortisol in human, corticosterone in rats and mice). The activity of HPA axis is regulated by a variety of negative feedback mechanisms including self-regulation by its end products cortisol and corticosterone, whose local concentration is modulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1). This enzyme elevates local (intracellular) concentration of biologically active form of glucocorticoid hormone due to reduction of biologically inactive corticosteroid derivatives presented in blood plasma. Our aim in this project is to explore the potential role of 11HSD1 in regulation of HPA axis in stressed rat.
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The functions of the gastrointestinal tract are controlled by a variety of regulatory networks including hormone, neural and immune signaling. These regulatory networks are essential for complex coordination of events that integrate barrier functions, digestion and transport with alterations in motility and the flow of blood and lymph in response to the daily fasting-feeding cycle and to the other physiological and pathophysiological conditions. The aim of this project is to analyze the changes of intestinal transport functions under normal and pathological conditions.
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There is growing evidence that gut microbiota have a modulatory effect on behavioral, neurochemical and immunological responses, especially on postnatal development of stress response and stress-related psychiatric disorders, often comorbid with a variety of other illnesses including diseases of the gastrointestinal tract. The purpose of this project is to clarify mechanisms of action involved in the effects of gut microbiota on brain neurochemistry, behavior and activation of the hypothalamus-pituitary-adrenal axis.
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Epidemiologic studies demonstrate that disturbed circadian rhythms, often observed in time-shift workers, are significantly associated with a higher cancer risk. The aim of this project is to identify the relationship between disruption of the internal time keeping system and cancer. These studies are of importance not only for understanding the ethiology of the disease but they are also of great significance for precaution of cancer and probably also for the effectiveness of cancer therapy (chronotherapy).
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Glucocorticoids exert anti-inflammatory and immunomodulatory effects that may be regulated in part by the activities of the glucocorticoid-activating and -inactivating enzymes, 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and type 2 (11HSD2), respectively. Exposure to proinflammatory stimuli such as TNF-α and IL-1β increases 11HSD1 in some cells, while inducing a decrease of 11HSD2 in others. These findings indicate that changes in 11HSD activity induced by proinflammatory cytokines might contribute to the feedback regulation of inflammation. The aim of the project is therefore to improve our understanding of the role of 11HSDs in inflammation.
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Publications
Polidarová, Lenka - Houdek, Pavel - Sládek, Martin - Novosadová, Zuzana - Pácha, Jiří - Sumová, Alena
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Mechanisms of hormonal regulation of the peripheral circadian clock in the colon
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Chronobiology International. 2017, roč. 34, 1, p. 1-16
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IF = 2.562
[ASEP]
[
doi
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Ergang, Peter - Vodička, Martin - Vagnerová, Karla - Moravec, Martin - Kvapilová, Pavlína - Kment, M. - Pácha, Jiří
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Inflammation regulates 11 beta-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system
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Steroids. 2017, roč. 126, Oct 2017, p. 66-73
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IF = 2.282
[ASEP]
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doi
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Soták, Matúš - Bryndová, Jana - Ergang, Peter - Vagnerová, Karla - Kvapilová, Pavlína - Vodička, Martin - Pácha, Jiří - Sumová, Alena
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Peripheral circadian clocks are diversely affected by adrenalectomy
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Chronobiology International. 2016, roč. 33, 5, p. 520-529
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IF = 2.562
[ASEP]
[
doi
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Szczurowska, Ewa - Ergang, Peter - Kubová, Hana - Druga, Rastislav - Salaj, M. - Mareš, Pavel
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Influence of early life status epilepticus on the developmental expression profile of the GluA2 subunit of AMPA receptors
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Experimental Neurology. 2016, roč. 283, Part A, p. 97-109
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IF = 4.706
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doi
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Svoboda, Jan - Telenský, Petr - Blahna, Karel - Vodička, Martin - Stuchlík, Aleš
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The role of rat posterior parietal cortex in coordinating spatial representations during place avoidance in dissociated reference frames on a continuously rotating arena (Carousel)
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Behavioural Brain Research. 2015, Vol. 292, -, p. 1-9
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IF = 3.002
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[
doi
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Behuliak, Michal - Vavřínová, Anna - Bencze, Michal - Polgárová, Kamila - Ergang, Peter - Kuneš, Jaroslav - Vaněčková, Ivana - Zicha, Josef
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Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar–Kyoto and spontaneously hypertensive rats
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Journal of Hypertension. 2015, Vol. 33, 12, p. 2443-2454
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IF = 5.062
[ASEP]
[
doi
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Ergang, Peter - Vodička, Martin - Soták, Matúš - Klusoňová, Petra - Behuliak, Michal - Řeháková, Lenka - Zach, P. - Pácha, Jiří
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Differential impact of stress on hypothalamic–pituitary–adrenal axis: Gene expression changes in Lewis and Fisher rats
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Psychoneuroendocrinology. 2015, Vol. 53, Mar 2015, p. 49-59
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IF = 4.704
[ASEP]
[
doi
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Vodička, Martin - Ergang, Peter - Mikulecká, Anna - Řeháková, Lenka - Klusoňová, Petra - Makal, J. - Soták, Matúš - Musílková, Jana - Zach, P. - Pácha, Jiří
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Regulation of 11 beta-Hydroxysteroid Dehydrogenase Type 1 and 7 alpha-Hydroxylase CYP7B1 during Social Stress
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PLoS ONE 2014, roč. 9, 2, e89421. ISSN 1932-6203.
IF = 3.234
[ASEP]
[
doi
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Soták, Matúš - Sumová, Alena - Pácha, Jiří
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Cross-talk between the circadian clock and the cell cycle in cancer
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Annals of Medicine 2014, roč. 46, 4, p. 221-232. ISSN 0785-3890.
IF = 3.886
[ASEP]
[
doi
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Polidarová, Lenka - Olejníková, Lucie - Paušlyová, Lucia - Sládek, Martin - Soták, Matúš - Pácha, Jiří - Sumová, Alena
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Development and entrainment of the colonic circadian clock during ontogenesis
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American Journal of Physiology-Gastrointestinal and Liver Physiology 2014, roč. 306, 4, g346-g356. ISSN 0193-1857.
IF = 3.798
[ASEP]
[
doi
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Moravec, Martin - Švec, Jiří - Ergang, Peter - Mandys, V. - Řeháková, Lenka - Zádorová, Z. - Hajer, J. - Kment, M. - Pácha, Jiří
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Expression of 11 beta-hydroxysteroid dehydrogenase type 2 is deregulated in colon carcinoma
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Histology and Histopathology 2014, roč. 29, 4, p. 489-496. ISSN 0213-3911.
IF = 2.096
[ASEP]
Mikšík, Ivan - Ergang, Peter - Pácha, Jiří
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Proteomic analysis of chicken eggshell cuticle membrane layer
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Analytical and Bioanalytical Chemistry 2014, roč. 406, 29, p. 7633-7640. ISSN 1618-2642.
IF = 3.436
[ASEP]
[
doi
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Hudcová, T. - Bryndová, Jana - Fialová, K. - Fiala, J. - Karabín, M. - Jelínek, L. - Dostalek, P.
Antiproliferative effects of prenylflavonoids from hops on human colon cancer cell lines
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Journal of the Institute of Brewing. 2014, roč. 120, 3, p. 225-230. ISSN 0046-9750.
IF = 1.24
[ASEP]
[
doi
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Ergang, Peter - Kuželová, A. - Soták, Matúš - Klusoňová, Petra - Makal, J. - Pácha, Jiří
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Distinct Effect of Stress on 11 beta-Hydroxysteroid Dehydrogenase Type 1 and Corticosteroid Receptors in Dorsal and Ventral Hippocampus
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Physiological Research 2014, roč. 63, 2, p. 255-261. ISSN 0862-8408.
IF = 1.293
[ASEP]
Soták, Matúš - Polidarová, Lenka - Ergang, Peter - Sumová, Alena - Pácha, Jiří
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An association between clock genes and clock-controlled cell cycle genes in murine colorectal tumors
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International Journal of Cancer, 2013, Vol. 132, 5, p. 1032-1041
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IF = 6.198
[ASEP]
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doi
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Pácha, Jiří - Sumová, Alena
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Circadian regulation of epithelial functions in the intestine
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Acta Physiologica, 2013, Vol. 208, 1, p. 11-24
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IF = 4.382
[ASEP]
[
doi
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Vagnerová, Karla - Loukotová, Jana - Ergang, Peter - Musílková, Jana - Mikšík, Ivan - Pácha, Jiří
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Peroxisome proliferator-activated receptor-gamma stimulates 11beta-hydroxysteroid dehydrogenase type 1 in rat vascular smooth muscle cells
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Steroids, 2011, Vol. 76, 6, p. 577-581
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IF = 2.829
[ASEP]
[
doi
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Soták, Matúš - Polidarová, Lenka - Musílková, Jana - Hock, Miroslav - Sumová, Alena - Pácha, Jiří
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Circadian regulation of electrolyte absorption in the rat colon
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American Journal of Physiology-Gastrointestinal and Liver Physiology, 2011, Vol. 301, 6, G1066-G1074
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IF = 3.431
[ASEP]
[
doi
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Polidarová, Lenka - Sládek, Martin - Soták, Matúš - Pácha, Jiří - Sumová, Alena
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Hepatic, Duodenal, and Colonic Circadian Clocks Differ in their Persistence under Conditions of Constant Light and in their Entrainment by Restricted Feeding
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Chronobiology International, 2011, Vol. 28, 3, p. 204-215
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IF = 4.028
[ASEP]
[
doi
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Klusoňová, Petra - Pátková, Lenka - Ergang, Peter - Mikšík, Ivan - Zicha, Josef - Kuneš, Jaroslav - Pácha, Jiří
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Local metabolism of glucocorticoids in Prague hereditary hypertriglyceridemic rats – Effect of hypertriglyceridemia and gender
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Steroids, 2011, Vol. 76, 12, p. 1252-1259
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IF = 2.829
[ASEP]
[
doi
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Hock, M. - Soták, Matúš - Kment, M. - Pácha, J.
The early effect of dextran sodium sulfate administration on carbachol-induced short-circuit current in distal and proximal colon during colitis development
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Physiological Research, 2011, Vol. 60, 6, p. 921-931
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IF = 1.555
[ASEP]
Ergang, Peter - Vytáčková, Kateřina - Švec, Jiří - Bryndová, Jana - Mikšík, Ivan - Pácha, Jiří
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Upregulation of 11beta-hydroxysteroid dehydrogenase 1 in lymphoid organs during inflammation in the rat
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Journal of Steroid Biochemistry and Molecular Biology, 2011, Vol. 126, 1-2, p. 19-25
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IF = 3.053
[ASEP]
[
doi
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Švec, J. - Ergang, Peter - Mandys, V. - Kment, M. - Pácha, Jiří
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Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models
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International Journal of Experimental Pathology, 2010, Vol. 91, 1, p. 44-53
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IF = 2.127
[ASEP]
[
doi
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Švec, J. - Musílková, Jana - Bryndová, Jana - Jirásek, T. - Mandys, V. - Kment, M. - Pácha, Jiří
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Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia
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Inflammatory Bowel Diseases, 2010, Vol. 16, 7, p. 1127-1137
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IF = 4.613
[ASEP]
[
doi
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Ergang, Peter - Leden, P. - Vagnerová, Karla - Klusoňová, Petra - Mikšík, Ivan - Jurčovičová, J. - Kment, M. - Pácha, Jiří
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Local metabolism of glucocorticoids and its role in rat adjuvant arthritis
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Molecular and Cellular Endocrinology, 2010, Vol. 323, 2, p. 155-160
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IF = 4.119
[ASEP]
[
doi
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Vacková, Z. - Vagnerová, Karla - Libra, A. - Mikšík, Ivan - Pácha, Jiří - Staud, F.
Dexamethasone and betamethasone administration during pregnancy affects expression and function of 11beta-hydroxysteroid dehydrogenase type 2 in the rat placenta
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Reproductive Toxicology, 2009, Vol. 28, 1, p. 46-51
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IF = 3.367
[ASEP]
[
doi
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Polidarová, Lenka - Soták, Matúš - Sládek, Martin - Pácha, Jiří - Sumová, Alena
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Temporal Gradient in the Clock Gene and Cell-Cycle Checkpoint Kinase Wee1 Expression along the Gut
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Chronobiology International, 2009, Vol. 26, 4, p. 607-620
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IF = 3.987
[ASEP]
[
doi
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Klusoňová, Petra - Řeháková, Lenka - Borchert, Gudrun H. - Vagnerová, Karla - Neckář, Jan - Ergang, Peter - Mikšík, Ivan - Kolář, František - Pácha, Jiří
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Chronic Intermittent Hypoxia Induces 11Beta-Hydroxysteroid Dehydrogenase in Rat Heart
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Endocrinology, 2009, Vol. 150, 9, p. 4270-4277
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IF = 4.752
[ASEP]
[
doi
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Benešová, Jana - Hock, Miroslav - Butenko, Olena - Prajerová, Iva - Anděrová, Miroslava - Chvátal, Alexandr
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Quantification of astrocyte volume changes during ischemia in situ reveals two populations of astrocytes in the cortex of GFAP/EGFP mice
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Journal of Neuroscience Research, 2009, Vol. 87, 1, p. 96-111
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IF = 2.986
[ASEP]
[
doi
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Vagnerová, Karla - Vacková, Z. - Klusoňová, Petra - Štaud, F. - Kopecký, M. - Ergang, Peter - Mikšík, Ivan - Pácha, Jiří
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Reciprocal Changes in Maternal and Fetal Metabolism of Corticosterone in Rat During Gestation
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Reproductive Sciences, 2008, Vol. 15, 9, p. 921-931
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IF = 1.951
[ASEP]
Mrnka, Libor - Hock, Miroslav - Rybová, Markéta - Pácha, Jiří
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Melatonin inhibits prostaglandin E2- and sodium nitroprusside-induced ion secretion in rat distal colon
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European Journal of Pharmacology, 2008, Vol. 581, 1-2, p. 164-170
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IF = 2.787
[ASEP]
Klusoňová, Petra - Kučka, Marek - Ergang, Peter - Mikšík, Ivan - Bryndová, Jana - Pácha, Jiří
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Cloning of chicken 11beta-hydroxysteroid dehydrogenase type 1 and its tissue distribution
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Journal of Steroid Biochemistry and Molecular Biology, 2008, Vol. 111, 3-5, p. 217-224
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IF = 2.827
[ASEP]
[
doi
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Klusoňová, Petra - Kučka, Marek - Mikšík, Ivan - Bryndová, Jana - Pácha, Jiří
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Chicken 11beta-hydroxysteroid dehydrogenase type 2: Partial cloning and tissue distribution
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Steroids, 2008, Vol. 73, 3, p. 348-355
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IF = 2.588
[ASEP]
Ergang, Peter - Leden, Pavel - Bryndová, Jana - Žbánková, Šárka - Mikšík, Ivan - Kment, M. - Pácha, Jiří
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Glucocorticoid Availability in Colonic Inflammation of Rat
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Digestive Diseases and Sciences, 2008, Vol. 53, 8, p. 2160-2167
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IF = 1.583
[ASEP]
[
doi
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Žbánková, Šárka - Bryndová, Jana - Leden, Pavel - Kment, M. - Švec, A. - Pácha, Jiří
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11beta-hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis
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Journal of Gastroenterology and Hepatology, 2007, Vol. 22, 7, p. 1019-1023
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IF = 1.673
[ASEP]
Stuchlík, Aleš - Řeháková, Lenka - Telenský, Petr - Valeš, Karel
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Morris water maze learning in Long-Evans rats is differentially affected by blockade of D1-like and D2-like dopamine receptors
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Neuroscience Letters, 2007, Vol. 422, 3, p. 169-174
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IF = 2.085
[ASEP]
Stuchlík, Aleš - Řeháková, Lenka - Rambousek, Lukáš - Svoboda, Jan - Valeš, Karel
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Manipulation of D2 receptors with quinpirole and sulpiride affects locomotor activity before spatial behavior of rats in an active place avoidance task
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Neuroscience Research, 2007, Vol. 58, 2, p. 133-139
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IF = 2.121
[ASEP]
Sládek, Martin - Rybová, Markéta - Jindráková, Zuzana - Zemanová, Zdeňka - Polidarová, Lenka - Mrnka, Libor - O´Neill, J. - Pácha, Jiří - Sumová, Alena
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Insight Into the Circadian Clock Within Rat Colonic Epithelial Cells
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Gastroenterology, 2007, Vol. 133, 4, p. 1240-1249
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IF = 11.673
[ASEP]
Matějčková, J. - Tůma, P. - Samcová, E. - Zemanová, Zdeňka
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Determination of uric acid in plasma and allantoic fluid of chicken embryos by capillary electrophoresis
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Journal of Separation Science, 2007, Vol. 30, 12, p. 1947-1952
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IF = 2.632
[ASEP]
Klusoňová, Petra - Zemanová, Zdeňka
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Characteristics of the compensatory renal growth of the remnant embryonic chick kidneys
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Physiological Research, 2007, Vol. 56, 5, p. 651-654
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IF = 1.505
[ASEP]
Isolated colonic crypt of rat.
Intracellular pH response in isolated colonic crypts of rat. The crypts were exposed to intracellular alkalinization by addition of NH4Cl followed by acidification after washing out the ammonium pulse.
