In unserem Institut wurde in vorangegangenen Studien der Nachweis für die Präsenz des Natrium-Glukose-Kotransporters (SGLT-1) im Pansenepithel von Schafen sowohl auf molekularbiologischer als auch auf funktioneller Ebene erbracht. Im Dünndarm von Monogastriern und Wiederkäuern hängt die Aktivität des SGLT-1 im Wesentlichen vom phylogenetischen Ernährungstyp (Wiederkäuer: Konzentrat-selektierer oder Rauhfutterkonsumenten), vom aktuellen Substratangebot und der Beeinflussung durch stoffwechselaktive Hormone ab. Es ist bekannt, dass bei vermehrter Aufnahme leicht verdaulicher Kohlenhydrate die Präsenz des intestinalen SGLT-1 erhöht ist. Eine Stimulation des SGLT-1 durch den intrazellulären Messenger cAMP ist beschrieben. Im Rattendünndarm wurde eine cAMP-vermittelte Erhöhung der Glukoseaufnahme durch pankreatisches Glukagon 29, enterisches Glukagon 37 und Adrenalin nachgewiesen. Die vorliegenden In-vitro- Studien am Pansenepithel waren der Frage gewidmet, inwiefern sich die bisher am Dünndarm untersuchten Regulationswege auf den ruminalen SGLT-1 übertragen lassen. Dies betraf im Einzelnen: - Phylogenetische Unterschiede bei der ruminalen SGLT-1-Aktivität zwischen verschiedenen Ernährungstypen (Schaf, Damwild) - Regulation des SGLT-1 durch kurzfristige Änderungen des Substratangebots - Steigerung der Glukoseaufnahme durch Hormone (Katecholamine u. Glukagon), Die Studien wurden mittels einer modifizierten Ussing-Kammer-Technik durchgeführt. Von Schafen und Damwild wurde die Tunica mucosa der Pansenepithelien präpariert und in Ussing-Kammern inkubiert. Nach einer einminütigen mukosalen Inkubation mit D-Glukose (einschließlich 14C-markierter Glukose) erfolgte die Bestimmung der Glukosekonzentration im Epithelzelllysat mittels Szintillationszählung der radioaktiv markierten Glukose. Der Einfluss verschiedener Substanzen auf die Glukoseaufnahme wurde durch entsprechende Vorinkubation untersucht. Es konnten folgende Befunde erhoben werden: - Die ruminale Glukoseaufnahme bei einer mukosalen Glukosekonzentration von 200 µM erfolgt bei Schafen zu ca. 60 % über den SGLT-1, bei Damwild betrug dieser Anteil nur etwa 25 %. - Eine mehrstündige Erhöhung des mukosalen Glukoseangebotes auf 10 mM resultierte in einer ca. 50%igen Steigerung der SGLT-1-vermittelten Glukoseaufnahme beim Schaf. - Die Hormone Glukagon 37 und Adrenalin bewirkten am Schafspansen eine deutliche Steigerung der SGLT-1-vermittelten Glukoseaufnahme. Glukagon 29 hatte einen geringen Effekt, während Noradrenalin die Glukoseaufnahme nicht nachweisbar beeinflusste. - Im Rahmen einer detaillierteren Charakterisierung des Adrenalineffektes konnte eine Stimulation des SGLT-1 auch durch den -Rezeptoragonist Isoproterenol und den 2-spezifischen Agonisten Terbutalin ausgelöst werden. Andere rezeptorspezifische Agonisten (alpha-1, alpha-2, beta-1 und beta-3) hatten keinen Einfluss. Schlussfolgernd lässt sich postulieren, dass der SGLT-1 bei Schafen der bedeutendste Transportmechanismus für die ruminale Glukoseaufnahme ist und bei Damwild im Gegensatz zu den vom Dünndarm bekannten Verhältnissen eine untergeordnete Rolle spielt. Eine Steuerung ist ähnlich wie im Dünndarm sowohl durch erhöhtes Glukoseangebot als auch durch Erhöhung der intrazellulären cAMP-Konzentration möglich. Die Hormone Adrenalin und Glukagon 37 stimulieren die Glukoseaufnahme in den getesteten Konzentrationen signifikant. Der Signalweg der Adrenalin-vermittelten Stimulation verläuft über Aktivierung der Adenylatzyklase und Proteinkinase A. Dafür scheint ein beta-2-Rezeptor im Pansenepithel verantwortlich zu sein. Die praktische Relevanz der untersuchten Stimulierbarkeit des SGLT-1 könnte in vivo in der schnellen Entfernung überschüssiger Glukosemengen aus dem Vormagen liegen, um eventuell einer bakteriellen Dysfermentation im Pansen entgegenzusteuern. / Recent studies evidenced the presence of the sodium / glucose cotransporter, SGLT-1, in ruminal epithelia of sheep and showed its ability to absorb glucose. Concerning the possibility of regulation of SGLT-1, the influence of substrate concentration has been reported in other tissues. There are phylogenetic adaptions according to the feeding habits of different ruminants (grass and roughage consumer, intermediate mixed feeder and concentrate selectors) and the possibility to short-term adaption in response to the availability of easely fermentable carbohydrates. Furthermore, some hormones are known to stimulate glucose uptake. The important role of cyclic AMP (cAMP) as an intracellular mediator and stimulator of glucose uptake is well described. There is evidence for the influence of hormones stimulating the SGLT-1 by rising the cAMP level. Stimulation of intestinal glucose uptake occured after preincubation with pancreatic glucagon (glucagon 29), enteric glucagon (glucagon 37) and epinephrine in the rat small intestine. To proove whether the regulatory priciples of the intestinal SGLT-1 apply also to the SGLT-1 in the ruminant forestomach, the heredescribed studies addressed the following topics: -Quantification of SGLT-1-mediated glucose uptake in the rumen of ruminants with different feeding habits (sheep vs. fallow deer) -Short-term regulation of glucose uptake by substrate availability -Modulation of glucose uptake by hormones with stimulatory effects on cAMP level Glucose uptake studies were performed in vitro using a modified Ussing chamber technique. Ruminal epithelia were incubated on the mucosal side with glucose (including 50 kBq 14C-glucose) for 1 min. Glucose content of the lysed epithelia was measured by scintillation counting. The influence of certain substances on glucose uptake was investigated by preincubation with these substances either on the serosal, mucosal or both sides of the epithelia. RESULTS - Ruminal glucose absorption in sheep is mediated to approximately 60 % by SGLT-1, whereas the SGLT-1 of fallow deer transports only 25 % of the glucose (at a mucosal glucose concentration of 200 µM). - After mucosal preincubation with 10 mM glucose for several hours, the SGLT-1-mediated glucose uptake of sheep rumen raised up to 150 %. - The hormones glucagon 37 and epinephrine increased SGLT-1-mediated glucose transport in the sheep rumen. A minor stimulation was also observed after addition of glucagon 29, whereas norepinephrine had no effect on glucose uptake. - The effect of epinephrine was characterized in detail. It could be simulated by using the beta-receptoragonist isoproterenol as well as the beta-2-receptor agonist terbutaline. No effect was observed with alpha-1-, alpha-2-, beta-1- and beta-3-receptor agonists. These results lead to the following conclusions: SGLT-1 is the most important transport mechanism for ruminal glucose uptake in sheep. In contrast to the high SGLT-1-activity in the intestine of fallow deer, there is only a minor relevance in the rumen of this species. A fast significant stimulation of the ruminal SGLT-1 of sheep in vitro is possible by rising glucose supply and serosal addition of epinephrine and glucagon 37 in the tested concentrations. Glucagon 29 and norepinephrine had no effect on SGLT-1 under the used experimental conditions. The intracellular signalling of the epinephrine action involves the pathway via adenylate cyclase and protein kinase A. The investigated effect of epinephrine is mediated by beta-2-adrenoceptors. The priciples of regulation of the ruminal SGLT-1 are similar to the intestine. Perhaps, in vivo, up-regulation of glucose absorption by substrates and hormones is important for a fast removal of excess glucose from rumen to prevent dysfermentation.

Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...

Spatial navigation, cognitive coordination and behavioral flexibility belong amongst cognitive functions, which play a role in many neuropsychiatric disorders. Behavioral tasks have proved to be useful paradigms to test these functions in pharmacological or genetic animal models. First aim was to determine a potential interaction between β-adrenergic and α1-adrenergic or D2-dopaminergic systems. Spatial navigation and coordination were impaired in both studies during co-aplication of subthreshold doses of drugs. Used substances belong to group of widely prescribed drugs, thus our results could be implicated in clinical practice. Another study examined an acute effect of MK-801 (animal model of schizophrenia) on behavioral flexibility in Carousel maze and the Morris water maze (MWM). Carousel maze showed higher sensitivity with impairments from 0.08 mg.kg-1 compared to 0.10 mg.kg- 1 in MWM. The final experiment aimed at testing the effect of reduced expression of Nogo-A protein on spatial navigation and behavioral flexibility of rats. A battery of tests in the Carousel maze revealed impairment in cognitive functions, MWM showed unaffected working memory of rats. Our results support the hypothesis linking Nogo-A knock-down rats with neuropsychiatric symptoms and cognitive disorders. Key words:...

Das EKG ist ein etabliertes und einfach durchzuführendes diagnostisches Routineverfahren. Belastungsuntersuchungen in denen das EKG beispielsweise Aufschluss über myokardiale Ischämien und Rhythmusstörungen geben kann, belegen den hohen diagnostischen Stellenwert des EKGs. Die Veränderungen der Parameter des EKGs sind charakteristisch und unterliegen dabei den unterschiedlichen physiologischen Bedingungen. Die vorliegende prospektive klinische Untersuchung beschäftigt sich mit der Fragestellung, welche physiologischen Bedingungen für diese Veränderungen ursächlich verantwortlich sind. Dazu wurden 10 männliche Probanden in 2 doppelten Stufen- und 2 Dauertests mit und ohne ß-Blockade untersucht. Es konnte festgestellt werden, dass in Ruhe und bei intensiver Belastung die ß-Blockade eine Wirkung hatte, was auf einen relevanten Einfluss des Sympathikus schließen lässt. Bei leichter und mittlerer Belastung und in der unmittelbaren Nachbelastungsphase waren hingegen keine Unterschiede in den Tests ohne und mit ß-Blockade festzustellen. Deshalb ist die Annahme plausibel, dass die Regulation der Herzfunktionen durch den Parasympathikus stattfindet, während der Sympathikus hier lediglich eine ergänzende Modulationsfunktion hat. Grundsätzlich unterstützt dies insgesamt die Theorie der zentralen Mitinnervation, die nach den vorliegenden Ergebnissen allerdings vorrangig in der Bedeutung des Parasympathikus und nachrangig in der des Sympathikus liegt.

Abstract The purpose of this study was to find out and compare the physiological effects of different types of non-hypothermic cold exposure tests in man. In whole-body cold exposures lightly clothed subjects were exposed to 10°C for 2 hours (single exposure), as well as repeatidly for 2 h and 1 h on ten successive days in separate studies. For local cold exposures, cold pressor tests (immersion into ice-cold water) of both hands and both feet were used. In whole-body cold exposures, several hormonal and metabolic parameters as well as cold sensations were measured. In local cold exposures the measured parameters were blood pressure, heart rate and skin temperatures. The single 2-h whole-body cold air exposure decreased rectal and skin temperatures and body heat content, but increased the metabolic rate. At the same time the serum noradrenaline concentration increased indicating a general activation of the sympathetic nervous system. Serum free fatty acid concentration increased whereas cortisol, GH and prolactin concentrations fell. No significant changes were found in serum concentrations of adrenalin, TSH, T3, T4, testosterone or LH. Serum total proteins were enhanced apparently due to cold-induced hemoconcentration. After repeating the 2-h whole-body cold exposure for five days the increase in serum noradrenaline level was markedly lower in the cold. At the same time hemoconcentration, judged from serum protein concentrations, was attenuated and the subjects became habituated to the cold sensations. However, the results showed that the repeated 1-h cold exposure in 10°C was not sufficiently intensive to reduce the noradrenaline response. Comparison of the hand and foot cold pressor tests to whole-body cold exposure tests showed that all tests caused significant increases in systolic and diastolic blood pressures, but that heart rate increased significantly only in the cold pressor test of feet. During the 2-h cold air exposure the heart rate fell. This caused a reduction in rate pressure product (RPP, the product of heart rate and systolic blood pressure). In both cold pressor tests the rate pressure product increased, indicating the enhancement of the O2-need in the heart muscle. The results showed no significant correlation in systolic or diastolic blood pressures between whole-body and local cooling of hands or feet. The lack of the association between local and whole-body cold exposure tests may be due to differences in severity and site of the tests: whole-body cold exposure tests cause general cold discomfort while cold pressor tests cause local cold pain. / Tiivistelmä Tämän tutkimuksen tarkoituksena oli selvittää ja verrata eri tyyppisten lievien kylmäaltistustestien fysiologisia vaikutuksia ihmiseen. Yksittäisessä koko kehon kylmäaltistuksessa koehenkilöt olivat kevyesti vaatetettuina kahden tunnin ajan 10°C:n lämpötilassa. Toistetussa koko kehon kylmäaltistuksessa koehenkilöt oleskelivat myös 10°C:n lämpötilassa kahden tai yhden tunnin ajan kymmenenä perättäisenä päivänä. Paikallisessa kylmäaltistuksessa käytettiin kylmävesitestiä (ns. cold pressor koe). Testi tehtiin sekä käsille että jaloille. Koko kehon kylmäaltistuksessa mitattiin useita hormonaalisia, aineenvaihdunnan ja lämpötasapainon vasteita, sekä verenpainetta ja sydämen syketiheyttä. Paikallisissa kylmäaltistuksissa mitattiin verenpainetta, sydämen syketiheyttä ja iholämpötiloja. Yksittäinen koko kehon kahden tunnin kylmäaltistus laski syvälämpötilaa, iholämpötiloja ja kehon lämpösisältöä. Samanaikaisesti kehon lämmöntuotanto kasvoi. Seerumin noradrenaliinipitoisuus lisääntyi ilmentäen sympaattisen hermoston tehostunutta aktivoitumista. Seerumin vapaiden rasvahappojen pitoisuus kasvoi, samoin kokonaisproteiinipitoisuus, mutta kasvuhormonin, kortisolin ja prolaktiinin osalta todettiin pitoisuuksien vähenemistä. Merkitseviä muutoksia ei tapahtunut seerumin adrenaliinissa, TSH:ssa, T3:ssa, T4:ssä, testosteronissa tai LH:ssa. Toistetussa kahden tunnin pituisessa kylmäaltistuksessa seerumin noradrenaliinipitoisuudessa tapahtunut kasvu oli merkitsevästi vähäisempää viiden päivän jälkeen. Samanaikaisesti seerumin proteiinipitoisuus kylmässä väheni ja kylmätuntemukset muuttuivat lievemmiksi. Sen sijaan yhden tunnin toistettu altistus 10°C:ssa ei ollut riittävän voimakas vähentämään kylmän aiheuttamaa veren noradrenaliinipitoisuuden kasvua. Verenpaineen ja sydämen syketiheyden reaktioita verrattiin samoilla koehenkilöillä yksittäisessä kahden tunnin koko kehon kylmäaltistuksessa ja kylmävesitesteissä. Kaikki nämä testit kohottivat merkitsevästi systolista ja diastolista verenpainetta. Sydämen syketiheys laski koko kehon kylmäaltistuksessa. Jalkojen kylmävesitestissä sydämen syketiheys nousi merkitsevästi, mutta käsien testissä tämä nousu ei ollut merkitsevä. Verenpaineen nousu koko kehon kylmäaltistuksessa ei korreloinut merkitsevästi paikallisissa kylmäaltistuksissa mitattuihin verenpaineen nousuihin. Selittävänä tekijänä tähän lienee näiden kylmäaltistusmuotojen erilaisuus. Lievä koko kehon kylmäaltistus aiheuttaa yleistä epämiellyttävyyttä, kun taas äkilliseen, nopean iholämpötilan laskun aiheuttamaan paikalliseen kylmäaltistukseen liittyy usein kiputuntemuksia.

Title: Model of training preparation for young future flyboarders Objectives: The objective of the work is to create a model of training preparation for young future flyboarders based on the empiricism of the most successful professional flyboarders. Methods: Ten intentionally selected respondents filled out the survey on their current sports specializations. Three of them were selected based on the frequency of specific and non-specific sports. Individual non- standardized interviews were conducted with them, which were based on direct verbal communication with the respondents. Results: We created a model of training preparation for young future flyboarders. The training preparation model is divided for children from six to nine years old, in which we recommend general sports training (gymnastics, athletics, swimming, sports games). For children from ten to twelve years old, we recommend trampoline jumping, high jumping, swimming, balance exercises, body strengthening and stretching. For children over the age of thirteen, we recommend starting to fly on a flyboard. Keywords: extreme sport, fly on water , water sport, training preparation, change of sport, adrenaline

v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...

Ape Boards is my own newly formed label, which manufactures snowboards and kiteboards. For this thing I have proposed a substantial logotype, which has a function as a unifying element across the whole brand and designs boards. Website (www.apeboards.com). A first collection of snowboards and kiteboards from which I had made 7 pieces for a thesis. Designs do not 'mass' lust, because the objective is not a big production or promotion, but based on what I liked. From the minimalism through the color geometry to the gorillas, according to which the brand was named.

v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...

Background: Medication-related interferences with measurements of catecholamines and their metabolites represent important causes of false-positive results during diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences are less troublesome with measurements by liquid chromatography with tandem mass-spectrometry (LC-MS/MS) than by other methods, but can still present problems for some drugs. Levodopa, the precursor for dopamine used in the treatment of Parkinson’s disease, represents one potentially interfering medication. Methods: Plasma and urine samples, obtained from 20 Parkinsonian patients receiving levodopa, were analysed for concentrations of catecholamines and their O-methylated metabolites by LC-MS/MS. Results were compared with those from a group of 120 age-matched subjects and 18 patients with PPGLs. Results: Plasma and urinary free and deconjugated (freeþconjugated) methoxytyramine, as well as urinary dopamine, showed 22- to 148-fold higher (P<0.0001) concentrations in patients receiving levodopa than in the reference group. In contrast, plasma normetanephrine, urinary noradrenaline and urinary free and deconjugated normetanephrine concentrations were unaffected. Plasma free metanephrine, urinary adrenaline and urinary free and deconjugated metanephrine all showed higher (P<0.05) concentrations in Parkinsonian patients than the reference group, but this was only a problem for adrenaline. Similar to normetanephrine, plasma and urinary metanephrine remained below the 97.5 percentiles of the reference group in almost all Parkinsonian patients. Conclusions: These data establish that although levodopa treatment confounds identification of PPGLs that produce dopamine, the therapy is not a problem for use of LC-MS/MS measurements of plasma and urinary normetanephrine and metanephrine to diagnose more commonly encountered PPGLs that produce noradrenaline or adrenaline.