This thesis provides an appraisal of the structure of clustering of metabolic phenotypes and evaluates the pathophysiological mechanisms underlying the relationship between urinary uric acid and albumin excretion. Two population-based studies were involved. In the first part, we used data obtained in a large representative cross-sectional survey in the Czech Republic (Czech post-MONICA study). We showed that the urinary albumin/creatinine ratio (uACR) was an independent factor for an increase in serum uric acid (SUA) levels in adults without manifest metabolic syndrome (MetS), but with 1-2 MetS component(s). Furthermore, SUA levels increased by the synergistic interaction of uACR with visceral adiposity and blood pressure, which may suggest obesity-related hypertension with altered renal hemodynamics as the primary mechanism. In the second part, we analyzed data captured in a representative population sample of French Canadians (CARTaGENE study) with more detailed urine biochemical analyses available. This study yielded two novel observations. First, we showed that the rs13129697 major T allele, which has been associated with increased SUA levels in our analysis as well as in prior publications, was associated with a paradoxical decrease in uACR. The reason for this discrepant finding is the...

This diploma thesis deals with the determination of creatinine using a combination of flow injection analysis (FIA) or high-performance liquid chromatography (HPLC) with pulse amperometry, an electrochemical technique based on the application of potential pulses on a gold working electrode. The determination was performed in a basic environment of borate buffer with creatinine concentration of 1∙10-4 mol∙l-1 . The lenght of the cleaning and activation pulse was optimized as well as the pH of the running buffer. A cleaning pulse of +1.8 V was first applied to the electrode for 100 ms, then an activation potential of -0.5 V was applied for 150 ms and then a measuring potential of +0.2 V for 300 ms. The optimal pH was selected as pH=9,4. Methanol and acetonitrile were added to the borate buffer to test whether creatinine could be determined in presence of these organic solvents and whether flow injection analysis could be transformed into HPLC. Methanol in the system caused peak deformation, acetonitrile did not cause the peak deformation in the system, at higher contents the baseline was destabilized. Furthermore, the calibration dependence in the range of concentrations from 2.5∙10-4 mol∙l-1 to 5∙10-6 mol ∙ l-1 was measured using PAD in combination with FIA. At higher concentrations, peaks splitted....

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In der vorliegenden Arbeit sollten die in der veterinärmedizinischen Literatur bisher diskutierten Ursachen für LJD bei Makropoden hinsichtlich ihrer tatsächlichen Bedeutung abgeklärt und die Eignung einer formalininaktivierten, bestandsspezifischen Adsorbatvakzine zur Prophylaxe von LJD getestet werden. Da LJD eine parodontale Erkrankung darstellt, wurden auch die für Entstehung einer humanen Parodontitis prädisponierenden Faktoren mit in die Untersuchung einbezogen. Es wurden Tupferproben zur bakteriologischen Untersuchung von insgesamt 15 gesunden und 11 an LJD erkrankten Kängurus entnommen. Dabei konnten gramnegative Anaerobier bei allen Tieren isoliert werden. Fusobacterium nucleatum wurde in 82% der von an LJD erkrankten und nur in 33% der von gesunden Tieren entnommenen Tupferproben nachgewiesen, womit sich ein signifikanter Zusammenhang (P < 0,05) zwischen diesem Erreger und LJD ergab. Weitere überwiegend bei erkrankten Makropoden nachgewiesene Anaerobier stellten Prevotella oris/oralis (bei 73% der LJD-Fälle und bei 40% der gesunden Tiere) sowie Capnocytophaga spp. (45% vs. 13%) dar. Bacteroides spp. und Porphyromonas gingivalis wurden – wenn auch nur mit 3 bzw. 2 Nachweisen – ausschließlich bei kranken Tieren isoliert. Fusobacterium necrophorum wurde jeweils in 27% der Kängurus gefunden und spielte damit in dieser Studie keine Rolle für die Entstehung von LJD. In Übereinstimmung mit der Literatur konnten Moraxella spp. ausschließlich bei gesunden Makropoden isoliert werden. Vertreter dieser Gattung gehören damit offensichtlich zur normalen Maulflora der Kängurus. Für die Zoos in Halle und Leipzig wurde eine formalininaktivierte, bestandsspezifische Adsorbatvakzine gegen die bei einem an LJD erkrankten Känguru des jeweiligen Bestandes isolierten gramnegativen Anaerobier hergestellt. 7 Tiere (2 Rote Riesenkängurus, 5 Bennettwallabies) des Leipziger Zoos und 6 Bennettkängurus des Zoos in Halle wurden geimpft, wobei Auffrischungsimpfungen nach 4 bzw. 8 Wochen und nach 6 bzw. 12 Monaten erfolgten. Die spezifischen AK gegen das Prüfantigen Fusobacterium necrophorum wurden im SLA bestimmt. Es konnte keine Erhöhung der AK-Titer induziert werden und auch die Todesrate infolge von LJD senkte sich während des Untersuchungszeitraumes von 42 Monaten in den beiden Zoos nicht. Die höchsten AK-Level (1:512 bis 1:2048) ließen sich im Serum von natürlich infizierten und letztendlich tödlich erkrankten Bennettwallabies des Zoos in Hoyerswerda feststellen. Der Nachweis von AK-Titern im Serum von nicht geimpften Jungtieren lässt vermuten, dass AK via Kolostrum oder Dottersackplazenta auf die Jungtiere übertragen werden. Die Untersuchungen hinsichtlich der Fütterung zeigten, dass im Zoo Leipzig eine azidotische Stoffwechsellage induziert wurde, was sich bei den Leipziger Bennettkängurus in einem mit 7,53 signifikant niedrigeren Vormagen-pH-Wert im Vergleich zu den Hallenser und Auer Tieren (8,25 und 8,38) offenbarte. Dies schlug sich auch in erhöhten K-, Cholesterol- und &#61537;-Amylasewerten im Serum der Leipziger Wallabies nieder, womit gezeigt werden konnte, dass sich diese Parameter offenbar auch bei Makropoden zur Diagnostik einer chronischen Azidose eignen. Die Versorgung der Bennettkängurus in Magdeburg und Halle mit Ca und P war zwar nicht ausreichend, spiegelte sich aber nicht in veränderten Blutwerten dieser Mengenelemente wider. Die Aktivität der AP nimmt mit zunehmenden Alter ähnlich wie bei anderen Tierarten ab. Ihre negative Korrelation mit dem Alter der Tiere war dabei hochsignifikant (P < 0,001, r = 0,77 bzw. 0,62). Beim direkten Vergleich gesunder mit an LJD erkrankten Tieren konnte weder eine Störung im Ca/P-Stoffwechsel noch eine Azidose in Verbindung zu LJD gebracht werden. In allen Zoos erfolgte eine Überversorgung mit Vitamin A, wobei die Bedarfswerte für Schaflämmer um das 3,5fache bis 41fache übertroffen wurden. Den Bedarfswerten am nächsten lagen die Versorgungswerte der Bennettkängurus vom TP Aue und der Östlichen Grauen Riesenkängurus vom Zoo Magdeburg, beides Bestände ohne LJD. Die ermittelten Retinolplasmakonzentrationen standen in keiner Beziehung zu den Vitamin-A-Gehalten im Futter, was darauf hindeutet, dass sich Retinolbestimmungen im Blutplasma ebenso wie bei anderen Tierarten nur in extremsten defizitären Situationen zur Einschätzung des Vitamin-A-Status eignen. Ob eine Hypervitaminose A für die Entstehung von LJD tatsächlich eine Rolle spielt, muss in zukünftigen Arbeiten unter Einbeziehung von Retinolesterbestimmungen in der Leber abgeklärt werden. Die Glukosewerte lagen mit 8,57 mmol/l (M. rufus) bzw. 6,51 mmol/l (M. rufogriseus) über den bisher bekannten Werten aus der Literatur. Da die Werte bei an LJD erkrankten Kängurus niedriger waren als bei gesunden Tieren, kann ein Diabetes mellitus als Ursache für LJD ausgeschlossen werden. Weder die Durchsicht von 144 Sektionsprotokollen noch die Bestimmung der Kreatinin- und Harnstoffkonzentration im Serum von an LJD erkrankten Tieren ließen einen Zusammenhang zwischen Erkrankungen der Nieren und LJD erkennen. 30 Tiere verendeten an LJD, wovon 20% auch an den Nieren erkrankt waren. Allerdings wiesen auch 16,7% der anderweitig gestorbenen Kängurus eine Nierenerkrankung auf. Die Serumkonzentrationen von Harnstoff bzw. Kreatinin der an LJD erkrankten Makropoden unterschieden sich nicht von den für die gesunden Roten Riesenkängurus (7,40 mmol bzw. 114 mmol/l) und Bennettwallabies (7,81 mmol/l bzw. 86 mmol/l) ermittelten Werten. Insgesamt 184 Sera von 107 Kängurus wurden auf AK gegen MaHV-1 und MaHV-2 mittels Neutralisationtest geprüft. Während 94,4% bzw. 97,2% der Roten Riesenkängurus serologisch positiv für MaHV-1 bzw. MaHV-2 waren, reagierten von den 71 überprüften Bennettkängurus nur 4 bzw. 3 Tiere positiv. Unter den Wallabies befanden sich auch 21 an LJD erkrankte Tiere, wovon lediglich 2 Tiere gegen MaHV-1 und 1 Tier gegen MaHV-2 eine Serokonversion zeigten. Die AK-Titer der Roten Riesenkängurus ließen keine Unterschiede zwischen gesunden und an LJD leidenden Tieren zu und die entnommenen Serumpaarproben von 5 zum Zeitpunkt der Blutentnahme an LJD leidenden Riesenkängurus zeigten kein einheitliches Verhalten im Sinne einer Serokonversion. Somit ließ sich der Verdacht, dass die Reaktivierung latenter Herpesinfektionen die Ursache für LJD sein könnte, nicht bestätigen. Im Ergebnis der vorliegenden Studie und im Zusammenhang mit den Angaben aus der Literatur stellt sich LJD primär als eine Infektion mit gramnegativen Anaerobiern dar, wovon Fusobacterium nucleatum, Bacteroides spp., Prophyromonas gingivalis und Fusobacterium necrophorum, Biovar A die größte Bedeutung haben dürften. Den Abschluss der Arbeit bilden Empfehlungen für die Haltung von Kängurus in zoologischen Einrichtungen und für die Therapie von LJD. Im Anhang finden sich Röntgenaufnahmen und Photographien von erkrankten und gesunden Makropoden. / The aim of this thesis was the investigation of the aetiology of Lumpy Jaw Disease (LJD) in macropods concentrating specifically on the causes of the diseases in current veterinary medicine literature and to evaluate the use of a group-specific Al(OH)3-adjuvanted, formalin-inactivated whole-cell vaccine for the control of LJD in kangaroos kept in zoos. LJD is regarded as periodontal disease, therefore the risk factors for the development of human periodontitis were also included in this study. The oral flora from 15 healthy macropods and 11 animals suffering from LJD was isolated. At least one anaerobic gram-negative bacterial species was found in swabs of each macropod. The occurrence of Fusobacterium nucleatum was associated with LJD (P < 0.05) by detecting this bacterium in 82% of the kangaroos suffering from LJD compared to only in 33% of the healthy animals. Prevotella oris/oralis and Capnocytophaga spp. were also predominantly found in diseased animals in comparison with healthy macropods (73% vs. 40% and 45% vs. 13% respectively). Bacteroides spp. and Porphyromonas gingivalis were isolated in only 3 and 2 kangaroos suffering from LJD, respectively. Contrary to previously published studies about LJD Fusobacterium necrophorum was not associated with LJD, as this anaerobe was detected in only 27% of the diseased as well as healthy macropods. Moraxella spp. seem to be a part of the normal oral flora of macropods and was found exclusively in healthy animals. 11 Red-necked Wallabies (Macropus rufogriseus) and 2 Red Kangaroos (Macropus rufus) were immunized with a group-specific Al(OH)3-adjuvanted, formalin-inactivated whole-cell vaccine containing previously in a kangaroo suffering from LJD isolated gramnegative anaerobs. The kangaroos were re-vaccinated after 1, 2, 6 and 12 months. Blood was collected from each animal at the same time. Antibodies were titrated against Fusobacterium necrophorum in an agglutination assay. The vaccine failed to induce increased levels of antibodies as well as to protect wallabies and kangaroos against LJD. As the highest antibody titres were detected in most severely diseased wallabies kept in the Hoyerswerda zoo, the protective role of the humoral immune response in LJD seems to be doubtful. The finding of detectable levels of antibodies in unvaccinated joeys supports the theory, that there is a transmission of antibodies from the mother to the offspring via colostrum or yolk-sac placenta. The diet of the Red-necked Wallabies in one zoo has induced an acidosis: The pH of the forestomach fluid collected by probang was lower in the animals of this zoo (pH = 7.53) than in the wallabies of two other zoos (pH = 8.25 and 8.38, respectively). Potassium, cholesterol and &#61537;-amylase were also higher in the blood of the animals of this zoo in comparison to the wallabies of the two other ones, hence these blood values seem to be helpful for the diagnosis of chronic acidosis in macropods. There was a calcium and phosphor deficiency in the nutrition of the wallabies in two zoos, but the blood concentration of both of these minerals was not changed. The activity of the ALP correlated negative with the age of the Bennett`s Wallabies (P < 0.001, r = -.77 and r = -.62 respectively, depending on the instruments). All of the above mentioned blood values showed no differences between healthy and diseased animals and could so far not support the assumption, that an imbalance in Ca and P metabolism or an acidosis are important factors for LJD. The macropods of all investigated zoos were fed on a diet rich in vitamin A ranging from the 3.5 to the 41fold requirement for lambs. The vitamin A content of the diets for the 2 collections without a history of LJD was the lowest in this study. These results raised the point, that a hypervitaminosis A could be a more predisposing factor for LJD than a vitamin A deficiency. Due to the fact the plasma retinol concentration was independent from the vitamin A content of the diet and so not helpful in diagnosis of a vitamin A deficiency or toxicity, further investigations regarding the role of vitamin A in the aetiopathogenesis of LJD should include measurements of the liver tissue content of retinol esters. The glucose plasma concentration of the healthy Red Kangaroos (8.57 mmol/l) as well as the Red-necked Wallabies (6.51 mmol/l) was higher than previously published values for macropods, but also higher than the results of the diseased animals in this study. Therefore diabetes mellitus can be ruled out as an underlying factor for LJD. The analysis of 144 pathological records showed, that 30 animals died because of LJD, 20% of them and 16.7% of the other 114 macropods had a concurrent kidney disease. The urea and creatinin concentration in serum samples of healthy animals was not higher than the values of diseased animals. In conclusion, these results suggest kidney diseases are not important for the development of LJD. Altogether 184 sera collected from 107 kangaroos were tested for antibodies against MaHV-1 and MaHV-2 using a neutralisation assay. The prevalence of the MaHV-1- as well as MaHV-2-antibodies was high among the Red Kangaroos (94.4% and 97.2% respectively), but low among the Red-necked Wallabies (5.6% and 4.2% respectively). Seroconversion for MaHV-1 was seen in 2 out of 21 wallabies suffering from LJD, only 1 of these animals also had antibodies against MaHV-2. The antibody-titres against both of the macropodid herpes viruses also did not differ between Red Kangaroos with and without LJD, therefore a reactivation of a latent herpesvirus infection does not appear to be causative for LJD. In summary, considering the results of this study and previously published literature LJD is an infectious disease caused by gramnegative anaerobic bacteria with Fusobacterium nucleatum, Bacteroides spp., Porphyromonas gingivalis and Fusobacterium necrophorum subsp. necrophorum being of most significance. Recommendations concerning the keeping of kangaroos in captivity and the management of LJD are listed in the conclusion of this thesis. Some radiographs and photos of diseased and healthy kangaroos are attached.

Creatine is nitrogen-containing organic acid which naturally occurs in the human body. The aim of this work was to determine the optimal dose of creatine in combination with vitamin C and magnesium for male respondents aged 18-26 years. They were divided into two groups differing in the creatine dosage. Group 1 took smaller dose of creatine (3 g per day) and group 2 higher dose of creatine (10 g per day). Both groups took both magnesium and vitamin C at constant doses throughout the study. The effects of significantly different dose of creatine in the individual groups were compared with each other in terms of the performance of individuals in the powerlifting, the anthropological changes and the overal metabolism of the intakes. In all disciplines of powerlifting, group 1 recorded higher average weight gains, which were not found to be statistically significant at a significance level of alpha 0,05. Anthropological changes were measured using the InBody 160 and a diagnostic measuring tape. In both cases, group 1 recorded better results than group 2, but these results were not statistically significant at a significance level of alpha 0,05. The total metabolism of the accepted dietary supplements was investigated through analytical methods. The urine of each respondent was regularly collected and subsequently analyzed during the research. Determination of creatinine, a creatine waste product, was performed by UV-VIS spectrophotometry using the Jaffe reaction. Vitamin C was analyzed by RP-HPLC. Magnesium was determined by the ICP-OES method. After creatine suplemantion of 3 per day, group 1 showed a slight increase in creatinine in the urine, but still in the physiological range. At the significance level alpha 0,05 there was no statistically significant difference. Group 2 showed an increase above the physiological limit which was already a statistically significant difference. Overall, creatine supplementation of 3 g per day has been found as a sufficient intake of creatine needed to build up muscle mass, increase energy metabolism and overall physical performance. The metabolization itself works very well and within the physiological values.

In der vorliegenden Arbeit sollten die in der veterinärmedizinischen Literatur bisher diskutierten Ursachen für LJD bei Makropoden hinsichtlich ihrer tatsächlichen Bedeutung abgeklärt und die Eignung einer formalininaktivierten, bestandsspezifischen Adsorbatvakzine zur Prophylaxe von LJD getestet werden. Da LJD eine parodontale Erkrankung darstellt, wurden auch die für Entstehung einer humanen Parodontitis prädisponierenden Faktoren mit in die Untersuchung einbezogen. Es wurden Tupferproben zur bakteriologischen Untersuchung von insgesamt 15 gesunden und 11 an LJD erkrankten Kängurus entnommen. Dabei konnten gramnegative Anaerobier bei allen Tieren isoliert werden. Fusobacterium nucleatum wurde in 82% der von an LJD erkrankten und nur in 33% der von gesunden Tieren entnommenen Tupferproben nachgewiesen, womit sich ein signifikanter Zusammenhang (P < 0,05) zwischen diesem Erreger und LJD ergab. Weitere überwiegend bei erkrankten Makropoden nachgewiesene Anaerobier stellten Prevotella oris/oralis (bei 73% der LJD-Fälle und bei 40% der gesunden Tiere) sowie Capnocytophaga spp. (45% vs. 13%) dar. Bacteroides spp. und Porphyromonas gingivalis wurden – wenn auch nur mit 3 bzw. 2 Nachweisen – ausschließlich bei kranken Tieren isoliert. Fusobacterium necrophorum wurde jeweils in 27% der Kängurus gefunden und spielte damit in dieser Studie keine Rolle für die Entstehung von LJD. In Übereinstimmung mit der Literatur konnten Moraxella spp. ausschließlich bei gesunden Makropoden isoliert werden. Vertreter dieser Gattung gehören damit offensichtlich zur normalen Maulflora der Kängurus. Für die Zoos in Halle und Leipzig wurde eine formalininaktivierte, bestandsspezifische Adsorbatvakzine gegen die bei einem an LJD erkrankten Känguru des jeweiligen Bestandes isolierten gramnegativen Anaerobier hergestellt. 7 Tiere (2 Rote Riesenkängurus, 5 Bennettwallabies) des Leipziger Zoos und 6 Bennettkängurus des Zoos in Halle wurden geimpft, wobei Auffrischungsimpfungen nach 4 bzw. 8 Wochen und nach 6 bzw. 12 Monaten erfolgten. Die spezifischen AK gegen das Prüfantigen Fusobacterium necrophorum wurden im SLA bestimmt. Es konnte keine Erhöhung der AK-Titer induziert werden und auch die Todesrate infolge von LJD senkte sich während des Untersuchungszeitraumes von 42 Monaten in den beiden Zoos nicht. Die höchsten AK-Level (1:512 bis 1:2048) ließen sich im Serum von natürlich infizierten und letztendlich tödlich erkrankten Bennettwallabies des Zoos in Hoyerswerda feststellen. Der Nachweis von AK-Titern im Serum von nicht geimpften Jungtieren lässt vermuten, dass AK via Kolostrum oder Dottersackplazenta auf die Jungtiere übertragen werden. Die Untersuchungen hinsichtlich der Fütterung zeigten, dass im Zoo Leipzig eine azidotische Stoffwechsellage induziert wurde, was sich bei den Leipziger Bennettkängurus in einem mit 7,53 signifikant niedrigeren Vormagen-pH-Wert im Vergleich zu den Hallenser und Auer Tieren (8,25 und 8,38) offenbarte. Dies schlug sich auch in erhöhten K-, Cholesterol- und &#61537;-Amylasewerten im Serum der Leipziger Wallabies nieder, womit gezeigt werden konnte, dass sich diese Parameter offenbar auch bei Makropoden zur Diagnostik einer chronischen Azidose eignen. Die Versorgung der Bennettkängurus in Magdeburg und Halle mit Ca und P war zwar nicht ausreichend, spiegelte sich aber nicht in veränderten Blutwerten dieser Mengenelemente wider. Die Aktivität der AP nimmt mit zunehmenden Alter ähnlich wie bei anderen Tierarten ab. Ihre negative Korrelation mit dem Alter der Tiere war dabei hochsignifikant (P < 0,001, r = 0,77 bzw. 0,62). Beim direkten Vergleich gesunder mit an LJD erkrankten Tieren konnte weder eine Störung im Ca/P-Stoffwechsel noch eine Azidose in Verbindung zu LJD gebracht werden. In allen Zoos erfolgte eine Überversorgung mit Vitamin A, wobei die Bedarfswerte für Schaflämmer um das 3,5fache bis 41fache übertroffen wurden. Den Bedarfswerten am nächsten lagen die Versorgungswerte der Bennettkängurus vom TP Aue und der Östlichen Grauen Riesenkängurus vom Zoo Magdeburg, beides Bestände ohne LJD. Die ermittelten Retinolplasmakonzentrationen standen in keiner Beziehung zu den Vitamin-A-Gehalten im Futter, was darauf hindeutet, dass sich Retinolbestimmungen im Blutplasma ebenso wie bei anderen Tierarten nur in extremsten defizitären Situationen zur Einschätzung des Vitamin-A-Status eignen. Ob eine Hypervitaminose A für die Entstehung von LJD tatsächlich eine Rolle spielt, muss in zukünftigen Arbeiten unter Einbeziehung von Retinolesterbestimmungen in der Leber abgeklärt werden. Die Glukosewerte lagen mit 8,57 mmol/l (M. rufus) bzw. 6,51 mmol/l (M. rufogriseus) über den bisher bekannten Werten aus der Literatur. Da die Werte bei an LJD erkrankten Kängurus niedriger waren als bei gesunden Tieren, kann ein Diabetes mellitus als Ursache für LJD ausgeschlossen werden. Weder die Durchsicht von 144 Sektionsprotokollen noch die Bestimmung der Kreatinin- und Harnstoffkonzentration im Serum von an LJD erkrankten Tieren ließen einen Zusammenhang zwischen Erkrankungen der Nieren und LJD erkennen. 30 Tiere verendeten an LJD, wovon 20% auch an den Nieren erkrankt waren. Allerdings wiesen auch 16,7% der anderweitig gestorbenen Kängurus eine Nierenerkrankung auf. Die Serumkonzentrationen von Harnstoff bzw. Kreatinin der an LJD erkrankten Makropoden unterschieden sich nicht von den für die gesunden Roten Riesenkängurus (7,40 mmol bzw. 114 mmol/l) und Bennettwallabies (7,81 mmol/l bzw. 86 mmol/l) ermittelten Werten. Insgesamt 184 Sera von 107 Kängurus wurden auf AK gegen MaHV-1 und MaHV-2 mittels Neutralisationtest geprüft. Während 94,4% bzw. 97,2% der Roten Riesenkängurus serologisch positiv für MaHV-1 bzw. MaHV-2 waren, reagierten von den 71 überprüften Bennettkängurus nur 4 bzw. 3 Tiere positiv. Unter den Wallabies befanden sich auch 21 an LJD erkrankte Tiere, wovon lediglich 2 Tiere gegen MaHV-1 und 1 Tier gegen MaHV-2 eine Serokonversion zeigten. Die AK-Titer der Roten Riesenkängurus ließen keine Unterschiede zwischen gesunden und an LJD leidenden Tieren zu und die entnommenen Serumpaarproben von 5 zum Zeitpunkt der Blutentnahme an LJD leidenden Riesenkängurus zeigten kein einheitliches Verhalten im Sinne einer Serokonversion. Somit ließ sich der Verdacht, dass die Reaktivierung latenter Herpesinfektionen die Ursache für LJD sein könnte, nicht bestätigen. Im Ergebnis der vorliegenden Studie und im Zusammenhang mit den Angaben aus der Literatur stellt sich LJD primär als eine Infektion mit gramnegativen Anaerobiern dar, wovon Fusobacterium nucleatum, Bacteroides spp., Prophyromonas gingivalis und Fusobacterium necrophorum, Biovar A die größte Bedeutung haben dürften. Den Abschluss der Arbeit bilden Empfehlungen für die Haltung von Kängurus in zoologischen Einrichtungen und für die Therapie von LJD. Im Anhang finden sich Röntgenaufnahmen und Photographien von erkrankten und gesunden Makropoden. / The aim of this thesis was the investigation of the aetiology of Lumpy Jaw Disease (LJD) in macropods concentrating specifically on the causes of the diseases in current veterinary medicine literature and to evaluate the use of a group-specific Al(OH)3-adjuvanted, formalin-inactivated whole-cell vaccine for the control of LJD in kangaroos kept in zoos. LJD is regarded as periodontal disease, therefore the risk factors for the development of human periodontitis were also included in this study. The oral flora from 15 healthy macropods and 11 animals suffering from LJD was isolated. At least one anaerobic gram-negative bacterial species was found in swabs of each macropod. The occurrence of Fusobacterium nucleatum was associated with LJD (P < 0.05) by detecting this bacterium in 82% of the kangaroos suffering from LJD compared to only in 33% of the healthy animals. Prevotella oris/oralis and Capnocytophaga spp. were also predominantly found in diseased animals in comparison with healthy macropods (73% vs. 40% and 45% vs. 13% respectively). Bacteroides spp. and Porphyromonas gingivalis were isolated in only 3 and 2 kangaroos suffering from LJD, respectively. Contrary to previously published studies about LJD Fusobacterium necrophorum was not associated with LJD, as this anaerobe was detected in only 27% of the diseased as well as healthy macropods. Moraxella spp. seem to be a part of the normal oral flora of macropods and was found exclusively in healthy animals. 11 Red-necked Wallabies (Macropus rufogriseus) and 2 Red Kangaroos (Macropus rufus) were immunized with a group-specific Al(OH)3-adjuvanted, formalin-inactivated whole-cell vaccine containing previously in a kangaroo suffering from LJD isolated gramnegative anaerobs. The kangaroos were re-vaccinated after 1, 2, 6 and 12 months. Blood was collected from each animal at the same time. Antibodies were titrated against Fusobacterium necrophorum in an agglutination assay. The vaccine failed to induce increased levels of antibodies as well as to protect wallabies and kangaroos against LJD. As the highest antibody titres were detected in most severely diseased wallabies kept in the Hoyerswerda zoo, the protective role of the humoral immune response in LJD seems to be doubtful. The finding of detectable levels of antibodies in unvaccinated joeys supports the theory, that there is a transmission of antibodies from the mother to the offspring via colostrum or yolk-sac placenta. The diet of the Red-necked Wallabies in one zoo has induced an acidosis: The pH of the forestomach fluid collected by probang was lower in the animals of this zoo (pH = 7.53) than in the wallabies of two other zoos (pH = 8.25 and 8.38, respectively). Potassium, cholesterol and &#61537;-amylase were also higher in the blood of the animals of this zoo in comparison to the wallabies of the two other ones, hence these blood values seem to be helpful for the diagnosis of chronic acidosis in macropods. There was a calcium and phosphor deficiency in the nutrition of the wallabies in two zoos, but the blood concentration of both of these minerals was not changed. The activity of the ALP correlated negative with the age of the Bennett`s Wallabies (P < 0.001, r = -.77 and r = -.62 respectively, depending on the instruments). All of the above mentioned blood values showed no differences between healthy and diseased animals and could so far not support the assumption, that an imbalance in Ca and P metabolism or an acidosis are important factors for LJD. The macropods of all investigated zoos were fed on a diet rich in vitamin A ranging from the 3.5 to the 41fold requirement for lambs. The vitamin A content of the diets for the 2 collections without a history of LJD was the lowest in this study. These results raised the point, that a hypervitaminosis A could be a more predisposing factor for LJD than a vitamin A deficiency. Due to the fact the plasma retinol concentration was independent from the vitamin A content of the diet and so not helpful in diagnosis of a vitamin A deficiency or toxicity, further investigations regarding the role of vitamin A in the aetiopathogenesis of LJD should include measurements of the liver tissue content of retinol esters. The glucose plasma concentration of the healthy Red Kangaroos (8.57 mmol/l) as well as the Red-necked Wallabies (6.51 mmol/l) was higher than previously published values for macropods, but also higher than the results of the diseased animals in this study. Therefore diabetes mellitus can be ruled out as an underlying factor for LJD. The analysis of 144 pathological records showed, that 30 animals died because of LJD, 20% of them and 16.7% of the other 114 macropods had a concurrent kidney disease. The urea and creatinin concentration in serum samples of healthy animals was not higher than the values of diseased animals. In conclusion, these results suggest kidney diseases are not important for the development of LJD. Altogether 184 sera collected from 107 kangaroos were tested for antibodies against MaHV-1 and MaHV-2 using a neutralisation assay. The prevalence of the MaHV-1- as well as MaHV-2-antibodies was high among the Red Kangaroos (94.4% and 97.2% respectively), but low among the Red-necked Wallabies (5.6% and 4.2% respectively). Seroconversion for MaHV-1 was seen in 2 out of 21 wallabies suffering from LJD, only 1 of these animals also had antibodies against MaHV-2. The antibody-titres against both of the macropodid herpes viruses also did not differ between Red Kangaroos with and without LJD, therefore a reactivation of a latent herpesvirus infection does not appear to be causative for LJD. In summary, considering the results of this study and previously published literature LJD is an infectious disease caused by gramnegative anaerobic bacteria with Fusobacterium nucleatum, Bacteroides spp., Porphyromonas gingivalis and Fusobacterium necrophorum subsp. necrophorum being of most significance. Recommendations concerning the keeping of kangaroos in captivity and the management of LJD are listed in the conclusion of this thesis. Some radiographs and photos of diseased and healthy kangaroos are attached.

<p>Увод: Хронична бубрежна инсуфицијенција (ХБИ) се дефинише као структурно или функционално оштећење бубрега у трајању од најмање три месеца и/или смањење јачине гломеруларне филтрације (ЈГФ) испод 60 мл/мин/1.73м2. У доступној литератури постоје различити подаци о присуству оралних манифестација код пацијената са ХБИ у квантитативном и квалитативном погледу. Стање бубрежне дисфункције праћено је променама у протоку и саставу пљувачке што је у последњој деценији допринело испитивању клиничких и лабораторијских показатеља бубрежне болести. Циљ: Циљ студије је био да се испита објективно стање оралне слузокоже, вредности рН, сијалометрије, концентрације урее, креатинина и секреторног имуноглобулина А пљувачке као и орални микробиолошки статус код пацијената са ХБИ. Материјал и методе: Узорак је био сачињен од 50 предијализних (31 мушкарца и 19 жена просечне старости 59,06&plusmn;14,30) и 25 хемодијализних пацијената (18 мушкараца и 7 жена просечне старости 54,92&plusmn;13,60) са постављеном дијагнозом ХБИ, заједно са 25 системски здравих испитаника компарибилних по полу и старости. Поред клиничког прегледа усне дупље спроведен је тест витроадхезије, одређивање интензитета саливације, рН вредности пљувачке и индекса крварења из интерденталне папиле (PBI). На узорцима сакупљене пљувачке, уз помоћ аутоматизованог система Beckman Coulter АУ480 спроведено је лабораторијско одређивање урее и креатинина методом спектрофотометрије и секреторног имуноглобулина А методом имунотурбидиметрије. За микробилошко испитивање коришћен је брис језика и техника оралног испирка. Резултати: Нису утврђене статистички значајне разлике између група према демографско-социјалним подацима. Предијализни испитаници су имали значајно веће присуство промена оралне слузокоже и оралних симптома. Просечне вредности клиренса креатинина су биле значајно мање код оболелих испитаника са бледилом оралне слузокоже, уремичним задахом, ксеростомијом и измењеним осећајем укуса у поређењу са испитаницима без наведених промена. Код предијализних су утврђене значајно смањене вредности сијалометрије према контролним групама и повећане pH вредности према групи здравих испитаника. Просечне концентрације урее и креатинина су се статистички значајно разликовале између испитиваних група. Умерена позитивна корелација је утврђена између серумских и пљувачних концентрација урее и креатинина код предијализних и креатинина код хемодијализних. Према просечним вредностима секреторног имуноглобулина А није било разлика између група. Код пацијената са ХБИ утврђено је значајно веће присуство гљива из рода Candida са предоминацијом non-albicans Candida врста. Закључак: Резултати истраживања указују на важност утврђивања клиничких карактеристика усне дупље код предијализних пацијената. Интензитет саливације, pH вредност и пљувачне концентрације уремијских токсина могу бити поуздани маркери бубрежног оштећења. Једноставан и неинвазиван приступ приликом узорковања пљувачке и поузданост лабораторијске анализе треба да допринесу широј примени пљувачке као компетитивним дијагностичким флуидом серуму. Техника оралног испирка је прецизна квантитативна метода за одређивање степена гљивичне колонизације.</p> / <p>Uvod: Hronična bubrežna insuficijencija (HBI) se definiše kao strukturno ili funkcionalno oštećenje bubrega u trajanju od najmanje tri meseca i/ili smanjenje jačine glomerularne filtracije (JGF) ispod 60 ml/min/1.73m2. U dostupnoj literaturi postoje različiti podaci o prisustvu oralnih manifestacija kod pacijenata sa HBI u kvantitativnom i kvalitativnom pogledu. Stanje bubrežne disfunkcije praćeno je promenama u protoku i sastavu pljuvačke što je u poslednjoj deceniji doprinelo ispitivanju kliničkih i laboratorijskih pokazatelja bubrežne bolesti. Cilj: Cilj studije je bio da se ispita objektivno stanje oralne sluzokože, vrednosti rN, sijalometrije, koncentracije uree, kreatinina i sekretornog imunoglobulina A pljuvačke kao i oralni mikrobiološki status kod pacijenata sa HBI. Materijal i metode: Uzorak je bio sačinjen od 50 predijaliznih (31 muškarca i 19 žena prosečne starosti 59,06&plusmn;14,30) i 25 hemodijaliznih pacijenata (18 muškaraca i 7 žena prosečne starosti 54,92&plusmn;13,60) sa postavljenom dijagnozom HBI, zajedno sa 25 sistemski zdravih ispitanika komparibilnih po polu i starosti. Pored kliničkog pregleda usne duplje sproveden je test vitroadhezije, određivanje intenziteta salivacije, rN vrednosti pljuvačke i indeksa krvarenja iz interdentalne papile (PBI). Na uzorcima sakupljene pljuvačke, uz pomoć automatizovanog sistema Beckman Coulter AU480 sprovedeno je laboratorijsko određivanje uree i kreatinina metodom spektrofotometrije i sekretornog imunoglobulina A metodom imunoturbidimetrije. Za mikrobiloško ispitivanje korišćen je bris jezika i tehnika oralnog ispirka. Rezultati: Nisu utvrđene statistički značajne razlike između grupa prema demografsko-socijalnim podacima. Predijalizni ispitanici su imali značajno veće prisustvo promena oralne sluzokože i oralnih simptoma. Prosečne vrednosti klirensa kreatinina su bile značajno manje kod obolelih ispitanika sa bledilom oralne sluzokože, uremičnim zadahom, kserostomijom i izmenjenim osećajem ukusa u poređenju sa ispitanicima bez navedenih promena. Kod predijaliznih su utvrđene značajno smanjene vrednosti sijalometrije prema kontrolnim grupama i povećane pH vrednosti prema grupi zdravih ispitanika. Prosečne koncentracije uree i kreatinina su se statistički značajno razlikovale između ispitivanih grupa. Umerena pozitivna korelacija je utvrđena između serumskih i pljuvačnih koncentracija uree i kreatinina kod predijaliznih i kreatinina kod hemodijaliznih. Prema prosečnim vrednostima sekretornog imunoglobulina A nije bilo razlika između grupa. Kod pacijenata sa HBI utvrđeno je značajno veće prisustvo gljiva iz roda Candida sa predominacijom non-albicans Candida vrsta. Zaključak: Rezultati istraživanja ukazuju na važnost utvrđivanja kliničkih karakteristika usne duplje kod predijaliznih pacijenata. Intenzitet salivacije, pH vrednost i pljuvačne koncentracije uremijskih toksina mogu biti pouzdani markeri bubrežnog oštećenja. Jednostavan i neinvazivan pristup prilikom uzorkovanja pljuvačke i pouzdanost laboratorijske analize treba da doprinesu široj primeni pljuvačke kao kompetitivnim dijagnostičkim fluidom serumu. Tehnika oralnog ispirka je precizna kvantitativna metoda za određivanje stepena gljivične kolonizacije.</p> / <p>Introduction: Chronic kidney disease (CKD) is defined as structural and functional kidney damage for a period of at least three months and/or reduction of glomerular filtration rate (GFR) under 60 ml/min/1.73m2. There are different data in the available literature in term of quantitative and qualitative presence of the oral manifestation in patients with CKD. Kidney dysfunction is accompanied by changes in the salivary flow and composition, which is in the last decade contributed by examination of clinical and laboratory markers of renal disease. Aim: The aim of the study was to examine condition of oral mucosa, pH value, salivary flow rate, concentration of salivary urea, creatinine, secretory immunoglobulin A and oral microbiological status in patients with CKD. Materials and Methods: The sample was consisted of 50 predialysis (31 males and 19 females, mean age 59,06&plusmn;14,30) and 25 hemodialysis patients (18 males and 7 females, mean age 54,92&plusmn;13,60) with a diagnosis of CKD, along with 25 age and gender matched healthy controls. In addition of clinical examination, tongue blade adhesion test, sialometry, salivary pH test and determination of papilla bleeding index (PBI) were conducted. Saliva samples were collected for laboratory analysis performed by automated system Beckman Coulter AU480. Levels of uremic toxins (urea and creatinine) and secretory immunoglobulin A were determinated by spectrophotometric and immunoturbidimetric method, respectively. Oral swab and oral rinse method were used for microbiological examination. Results: The sociodemographic characteristics of the patients with CKD and healthy controls showed no significant differences. Predialysis subjects had significantly higher presence of oral mucosa changes and oral symptoms. Mean values of creatinine clearence were significantly lower in patients with oral mucosa pallor, uremic fetor, xerostomia and disguesia, compared to patients without listed symptoms. Predialysis patients showed significantly decreased salivary flow rate compared to both control groups and significantly increased pH values compared to healthy controls. Mean concentrations of salivary urea and creatinine were statistically different between the groups. Moderate positive correlation was determined between serum and salivary levels of urea and creatinine in predialysis patients and creatinine in hemodialysis patients. Statistical analysis showed no differences between groups in mean concentration of secretory immunoglobulin A. The rate of oral fungal colonisation was significantly higher in CKD patients with predominance of non-albicans Candida species. Conclusion: The results of the present study indicate the importance of determining the clinical characteristics of oral cavity in predialysis patients. Saliva flow rate, pH value and salivary concentration of uremic toxins could be reliable markers of kidney disease. Simple and non-invasive approach due to saliva sampling and reliability of laboratory test should contribute to a wider application of saliva as a competitive diagnostic fluid. Oral rinse technique is an accurate quantitative method for determining the rate of fungal colonization.</p>

<p>Akutno bubrežno o&scaron;tećenje je česta i ozbiljna komplikacija nakon hirur&scaron;ke rekonstrukcije abdominalne aorte. Ona produžuje, poskupljuje bolničko lečenje i povećava morbiditet i mortalitet bolesnika. &Scaron;to ranije prepoznavanje bolesnika koji su pod povi&scaron;enim rizikom uz pomoć prediktivnih faktora, kao i identifikovanje akutnog bubrežnog o&scaron;tećenja od velikog je značaja za pravovremeno započinjanje preventivnih i terapijskih mera i smanjenje mortaliteta ovih bolesnika. Cilj istraživanja: Utvrditi incidencu akutnog bubrežnog o&scaron;tećenja, najznačajnije preoperativne i intraoperativne prediktivne faktore za nastanak akutnog bubrežnog o&scaron;tećenja i utvrditi da li serumski cistatin C ranije i preciznije ukazuje na akutno bubrežno o&scaron;tećenje u odnosu na serumski kreatinin 72 sata nakon elektivnih operacija na infrarenalnom segmentu aorte. Metodologija: Na Klinici za anesteziju, intenzivnu terapiju i terapiju bola i Klinici za vaskularnu i transplantacionu hirurgiju Kliničkog centra Vojvodine sprovedeno je prospektivno opservaciono istraživanje u trajanju od 18 meseci, od oktobra 2017. do aprila 2019. godine. U istraživanje je uključeno 140 pacijenata koji su podvrgnuti elektivnom operativnom zahvatu na infrarenalnom segmentu aorte. Preoperativni i intraoperativni potencijalni prediktivni faktori identifikovani su iz medicinske dokumentacije: istorije bolesti, protokoli anestezije, dnevne terapijske liste, liste vitalnih parametara i liste laboratorijskih parametara. Nastanak ABO je potvrđivan pomoću AKIN klasifikacionog sistema. Tokom postoperativnog perioda lečenja od 72 sata obraćana je pažnja na vreme i stepen nastanka ABO. Za statističku obradu podataka kori&scaron;ćen je program SPSS, verzija 21 (IBM SPSS, Čikago, Ilinois). Rezultati su predstavljeni tabelarno i grafički, a statistički značajnim su se smatrale vrednosti nivoa značajnosti p&lt;0,05. Podaci su obrađivani standardnim statističkim testovima. Za dobijanje modela predikcije primenjena je multivarijantna logistička regresija. Rezultati: Incidenca akutnog bubrežnog o&scaron;tećenja nakon elektivnih operacija na infrarenalnom segmentu aorte na Klinici za anesteziju, intenzivnu terapiju i terapiju bola i Klinici za vaskularnu i transplantacionu hirurgiju Kliničkog centra Vojvodine iznosi 28,56%. Prema ROC analizi granična vrednost koncentracije cistatina C od 1,14 mg/l ima najvi&scaron;u senzitivnost (82,5%), i specifičnost (76%) u diferenciranju bolesnika koji će dobiti akutno bubrežno o&scaron;tećenje. Kompletan model predikcije ABO nakon elektivnih operacija na infrarenalnom segmentu aorte sadrži sledeće faktore: prisustvo hronične bubrežne slabosti, preoperativna serumska koncentracija cistatina C &gt;1,14 mg/l, primena koloida u volumenu &gt;500 ml u toku operacije, ukupni volumen nadoknade u intraoperativnom periodu &gt;59 ml/kg. Zaključak: Incidenca akutnog bubrežnog o&scaron;tećenja nakon elektivnih operacija na infrarenalnom segmentu aorte na Klinici za anesteziju, intenzivnu terapiju i terapiju bola i Klinici za vaskularnu i transplantacionu hirurgiju Kliničkog centra Vojvodine je ne&scaron;to vi&scaron;a u odnosu na literaturne podatke. Cistatin C je bolji prediktor i pokazatelj akutnog bubrežnog o&scaron;tećenja u odnosu na kreatinin. Bolesnici koji imaju hroničnu bubrežnu slabost, preoperativni nivo cistatina C&gt;1,14 mg/l, koji tokom operacije dobiju preko 500 ml koloidnih rastvora, i ukupni volumen nadoknade &gt;59 ml/kg imaju veću &scaron;ansu da dobiju akutno o&scaron;tećenje bubrega u postoperativnom periodu.</p> / <p>Acute kidney injury is frequent and serious complication after aortic surgery which increases length of hospital stay, costs, morbidity and mortality. Earlier recognition of patients at risk by predictive factors and identification of acute kidney injury could have important role on right timing of preventive and therapeutic measures and lower mortality of these patients. Aims: to investigate the incidence of acute kidney injury, the most important preoperative and intraoperative predictive factors for acute kidney injury, and check whether cystatin C indicates acute kidney injury earlier and more accurately than creatinine 72 hours after elective infrarenal aortic surgery. Methodology: This prospective observational study was performed at Clinic of Anesthesia, Intensive Care and Pain Therapy and Clinic of Vascular and Transplantation Surgery, Clinical Centre of Vojvodina, during the period of 18 months, from October 2017 till April 2019. It includes 140 adult patient who underwent elective infrarenal aortic surgery. Potential predictive factors were identified out of medical records such as: patient history, anesthesia lists, daily therapeutic lists, vital parameters and laboratory values lists. The occurrence of acute kidney injury was noted according to AKIN criteria. IBM SPSS version 21 (Chicago, Illinois) was used for statistical analysis. The results were presented in tables and graphs, statistical significance was set at p value of less than 0,05. Standard statistical tests were applied. Multivariate logistic regression model was used for potential predictive factors. Results: The incidence of acute kidney injury at Clinic of Anesthesia, Intensive Care and Pain Therapy and Clinic of Vascular and Transplantation Surgery, Clinical Centre of Vojvodina, was 28,56%. The cut off value of cystatin C serum concentration of 1,14 mg/l has the highest sensitivity (82,5%), and specificity (76%) in the differentiation of patients who will develop acute kidney injury. The final model for predicting acute kidney injury in patients who underwent elective infrarenal aortic surgery contains the following variables: presence of chronic kidney failure, preoperative serum concentration of cystatin C&gt;1,14 mg/l, application of colloid solutions in volume&gt;500 ml during the operation and total intravascular fluid replacement volume&gt;59 ml/kg in intraoperative period. Conclusion: The incidence of acute kidney injury at Clinic of Anesthesia, Intensive Care and Pain Therapy and Clinic of Vascular and Transplantation Surgery, Clinical Centre of Vojvodina, is somewhat higher comparing to world literature data. Patients who are more likely to develop acute kidney injury have: chronic kidney failure, preoperative serum concentration of cystatin C&gt;1,14 mg/l and get colloid solutions in volume&gt;500 ml and total intravascular fluid replacement volume&gt;59 ml/kg during intraoperative period.</p>

Capillary zone electrophoresis is frequently used in various analyses. In this diploma thesis a hydrodynamic sample introduction method controlled by pressure pulse has been proposed for short-capillary electrophoresis. The base electrolyte flushes sample from the loop of a six-way sampling valve and is carried to the injection end of the capillary. At the time when the sample zone reached the capillary, a short pressure impulse is generated in the electrolyte stream, which provides injection of the sample into the capillary. Then the electrolyte flow is stopped and the separation voltage is turned on. The amount of sample introduced to the capillary is controlled by the duration of the pressure pulse. This new sample introduction method was tested in the determination of ammonia, histidine, creatinine, uric acid and hippuric acid in human urine and for rapid screening of the contents of the inorganic ions in cerebrospinal fluid and blood plasma. The determination was performed in a capillary with an overall length of 10,5 cm and two base electrolytes was tested - 50 mM MES + 5 mM NaOH (pH 5,10) and 1 M acetic acid + 1,5 mM crown ether 18-crown-6 (pH 2,40). Using dual detection techniques contactless conductivity and UV spectrometric detection, anorganic and organic substances in the sample could...