Academic literature on the topic 'Laktat Dehydrogenase'

Preeclampsia is the cause of maternal deaths that high after bleeding. Lactate dehydrogenase (LDH) useful as biochemical markers to describe the severity of the preeclampsia-eclampsia. Aim of this study is to find out the relationship of lactate dehydrogenase levels with preeclampsia-eclampsia degrees in RSUP DR.M.Djamil Padang 2017. Methods od this research is observational analytic uses secondary data derived by medical record. The place of study was carried out at the medical record installation of central general hospital DR.M.Djamil Padang. The time of the study wasconducted in December 2018 - January 2019. The sample is preeklampsia-eklampsia patients these being treated in installation of inpatient and installation of outpatient in central general hospital DR.M.Djamil Padang 2017 which meets the criteria of inclusion and exclusion and drawn using simple random sampling techniques amounted to 32 people.Univariate analysis is presented in the form of tables and bivariate analysis was presented in the form af a table using the Spearman test. Results : Based on the research results obtained severe preeclampsia patients 21 persons (65,6%) have average levels of lactate dehydrogenase 979,05 u/l with range 313-1755 and eclampsia patients 11 persons (34,4%) have average levels of lactate dehydogenase 1838,64 u/l with range 420-5508. Spearman correlation tst obtained significant value of 0.001 and correlation 0,545. Conclusion : There is a relationship between the levels of lactate dehydrogenase with degree preeclampsia-eclampsia (p<0,05) with medium correlation (r=0,545)

Zusammenfassung. In den vergangenen Jahrzehnten hat sich die Zahl der Ultraläufer vervielfacht, und viele Studien haben den Einfluss auf den Bewegungsapparat untersucht. Wir stellen die Erkenntnisse zu Schäden zusammen, die ein Ultramarathon an Gelenken und Muskeln verursachen kann. Die häufigsten Verletzungen bzw. Überlastungsschäden betreffen die untere Extremität, wobei Sprunggelenk und Knie am häufigsten betroffen sind. Bei sehr langen Läufen kommt es zu einer Anpassung mit Verdickung von Sehnen und Knorpel. Ein Ultramarathon kann zu einem ausgeprägten Muskelschaden führen, mit einem Anstieg von myozellulären Metaboliten wie Myoglobin, Laktat-Dehydrogenase und Creatinkinase.

AbstrakSianida telah digunakan sebagai senyawa toksik selama beberapa dekade untuk penangkapan ikan. Pengetahuan para nelayan yang rendah dapat menyebabkan kelebihan dosis penggunaan senyawa sianida. Hal ini dapat menyebabkan kematian ikan dan bahkan kerusakan terumbu karang. Sodium sianida tidak bersifat bioakumulasi dan biomagnifikasi berdasarkan nilai Kow-nya dan sebagian besar metabolit dikeluarkan melalui urin dalam bentuk thiosianat, SCN- (60-80%), 2-aminothiazoline-4-carboxylic acid (ATCA) atau 2-iminothiazolidine-4-carboxylic acid, ITCA (15%), serta gas HCN dan CO2. Biomarker organisme yang terpapar sianida yaitu kandungan CN-, SCN-,ATCA atau ITCA pada urin dan darah; perubahan histopatologis di limpa, hepato-renal dan ginjal; penurunan aktivitas enzim katalase pada jaringan hati, insang, otak, dan otot ikan; perubahan aktivitas laktat dehydrogenase (LDH) dan suksinat dehydrogenase (SDH), tingkah laku, laju respirasi, dan metabolit (asam piruvat dan asam laktat). Akan tetapi, aktivitas enzim dan struktur histopatologis kembali normal setelah pemulihan selama 14 hari di medium bebas NaCN. Paparan NaCN juga dapat menyebabkan perubahan kecepatan renang dan durasi surfacing behavior. Konsentrasi sianida di lingkungan tidak bisa diabaikan, sebab dimungkinkan adanya efek sinergis dan juga penghambatan sistem enzim katalase, yang pada akhirnya terjadi kerentanan organisme akuatik terhadap toksisitas sianida. Labeo rohita merupakan spesies ikan air tawar yang paling sensitif terhadap paparan NaCN, dengan nilai LC50 sebesar 0,32 mg/L (tanpa melihat jenis aliran yang digunakan).AbstractCyanide has been used as a toxic compound for decades for fishing. Lack of knowledge of fishermen can lead to overdosing use of a compound. This can lead to fish kills and even damage the coral reefs. Sodium cyanide is not bioaccumulative and biomagnificative based on the value of Kow and most metabolites are excreted in the urine in the form of SCN- (60-80%), 2-aminothiazoline-4-carboxylic acid, ATCA or 2-iminothiazolidine-4-carboxylic acid, ITCA (15%), as well as HCN gas and CO2. Biomarkers organisms are exposed cyanide content of CN-, SCN-, ATCA or ITCA on urine and blood; histopathological changes in spleen, hepato-renal and kidney; decreased activity of catalase enzyme in the liver, gills, brain, and muscles of fish; lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activity changes, behavioral, respiratory rate, and metabolites (pyruvic acid and lactic acid). However, the enzyme activity and histopathological structure back to normal after recovery for 14 days at NaCN-free medium. NaCN exposure can also cause changes in swimming speed and duration of surfacing behavior. The concentration of cyanide in the environment can not be ignored, because it is possible the existence of a synergistic effect and also the inhibition of catalase enzyme system, which eventually happened vulnerability of aquatic organisms to cyanide toxicity. Labeo rohita is a freshwater fish species are most sensitive to exposure to NaCN, with LC50 values of 0.32 mg / L (regardless of the type of flow used).

Zusammenfassung Ziel: Es soll die Wertigkeit von 123l-mlBG-Szintigraphie, Knochenszintigraphie und Katecholaminmetaboliten bei der Verlaufskontrolle untersucht werden. Methode: Es wurden 19 Kinder mit Neuroblastom im Stadium IV retrospektiv mit 123l-mlBG- und 99mTc-MDP-Szintigraphie untersucht und deren Ergebnisse mit der Bestimmung von Homovanillinsäure, Vanillinmandelsäure, neuronenspezifische Enolase, Laktat-dehydrogenase und Ferritin über einen Beobachtungszeitraum von 7-132 (Median: 36) Monaten verglichen. Ergebnisse und Schlußfolgerung: Die Ergebnisse zeigen, daß die Wertigkeit der einzelnen Verfahren vom Zeitpunkt des diagnostischen Einsatzes abhängig ist. Prinzipiell ist die mlBG-Szintigraphie das Verfahren mit der höchsten diagnostischen Aussagekraft. Zum prätherapeutischen Staging und zur Diagnostik des Rezidivs ist die Kombination aller drei Methoden sinnvoll. Bei der Verlaufskontrolle unter Chemotherapie spiegelt die mlBG-Szintigraphie die Heterogenität des Therapieeffektes am besten wider. Die Laborparameter eignen sich zum Therapiemonitoring wenig; der diagnostische Zugewinn durch die Skelettszintigraphie ist umstritten.

Ten puppies of the German shepherd breed at the age of up to 60 days were divided into two groups – control and experimental. The influence of low-frequency electromagnetic radiation of “PARKES-L” device on the indexes of exchange of proteins, fats, carbohydrates and activity of key enzymes of carbohydrate and protein exchange: aspartat-aminotransferase, alanine-aminotransferase and laktat dehydrogenase were determined. The “PARKES-L” device which has the range of working frequencies from 0,1 hertz to 30 kHz, the action of device is based on the reflex mechanism of action of weak low-frequency electromagnetic impulses on the receptors of skin (biologically active areas) of animals. The effect of device is obtained due to radiation of electromagnetic impulses by infrared light-emitting diodes, which are at the back and front sides of the device. It was determined that under the influence of electromagnetic radiation the processes of intermediate exchange of organic compounds are not changed, but anabolic processes in tissues increase which are in the process of growth and development of puppies. Therefore, till the end of the experiment it was determined that living mass of puppies of experimental group exceeded control group by 580 grams. We also proved that under the influence of electromagnetic radiations the use of nitrogen contained metabolites increased, taking into account the increase of whole protein concentration and protein fractions. Energy exchange also gets better due to the increase of aerobic oxidation that is confirmed by the increase of oxidizing phosphorylating reaction and reliable increase of kreatinin concentration. The increase of lipid fractions (triglycerides and phosphatides) and concentration of lipid fractions also confirm the strengthening of anabolic processes in tissues. It was determined by the research the increase of free amino acid in blood of puppies of experimental group on the background of diminishing of nitrogen ammonia level that is related to the increase of biosynthesis of amino acid in tissues by the mechanism of amination of keto-acids due to better use of non-protein nitrogen. Under the influence of “PARKES-L” radiation the activity of aminotransferase (aspart-aminotransferase, alanine-aminotransferase and laktat-dehydrogenase) increased for certain (Р ˂ 0.001) that testifies the increase of exchange of proteins and carbohydrates level. It is determined in our research that the influence of low-frequency electromagnetic radiation stimulates the growth and development of puppies of the German shepherd breed. Functional activity of the systems of haemopoiesis, digestion and processes of biosynthesis of proteins, fats and carbohydrates and also activity of key enzymes of protein and carbohydrate exchanges increased under the influence of “PARKES-L” device.

Analyses of haematological and biochemical constituents were carried out on the Norwegian subspecies of free-ranging red deer (Cervus elaphus atlanticus). All animals were captured from January to March by using a mixture of xylazine and tiletamin-zolazepam. Immobilisation was performed with plastic projectile syringes fired from a dart gun. Fourteen haematological parameters were analysed. There were no differences in the values between hinds and stags and between adults and calves (P > 0.01). Of the 22 biochemical compounds investigated there was a significant difference (P < 0.01) between calves and adults for lactate dehydrogenase (LD), globulin, beta globulin, gamma globulin, and the minerals Na, K, Mg, Zn, Ca, and P. Differences (P < 0.01) between hinds and stags were found in cholesterol, gamma glutamyl transferase (GGT), alpha-1 globulin, alpha-2 globulin and Cu. The blood values determined in this study can be used as reference values for this red deer subspecies immobilised with a mixture of xylazine-tiletamin-zolazepam for health control and diagnosis of diseases.Abstract in Norwegian /Sammendrag:Hematologiske og biokjemiske parametere er analysert på norsk frittlevende hjort (Cervus elaphus atlanticus). Hjorten ble immobilisert i tidsrommet januar til mars ved hjelp av et spesialgevær ladet med plast kanyler som inneholdt en blanding av xylazin og tiletamin-zolazepam. Det var ingen forskjeller i de14 undersøkte hematologiske verdiene mellom hinder, kalver og bukker (P>0,01). Av de 22 biokjemiske parametrene som ble undersøkt var det en signifikant forskjell mellom kalver og voksne (P<0,01) når det gjelder laktat dehydrogenase, globulin, beta globulin, gamma globulin og mineralene Na, K, Mg, Zn, Ca og P. Det var en signifikant forskjell mellom hinder og bukker (P<0.01) på parametrene kolesterol, gamma glutamyl transferase, alfa-1 globulin, alfa-2 globulin og Cu. Blodverdiene som ble målt i dette studiet kan bli brukt som referanseverdier for norsk hjort som er immobilisert med blandingen xylazin-tiletamin-zolazepam for helsekontroll og for diagnostisering av sykdommer.

Abstract : This study was designed to evaluate the anti-diabetic activity of the ethanol extract of Syzygium cumini leaves in alloxan-induced diabetes mice. The anti-diabetic activity of EDS was investigated in mice (Mus musculus SW.) Alloxan-induced diabetes. The effect of ethanol extract of Syzygium cumini leaves on normal blood glucose levels and oral glucose tolerance tests were studied in normoglycemic mice while the anti-diabetic effect was evaluated in alloxan-induced hyperglycemic mice. Ethanol extract of Syzygium cumini leaves (200 and 400 mg/kg) is given orally for 21 days. Glibenclamide (5 mg/kg, oral for 21 days) is used as a reference standard. Giving ethanol extract of Syzygium leaves causes a significant decrease in blood glucose levels in normoglycemic and hyperglycemic mice and also increases glucose tolerance test. Ethanol extract of Syzygium leaves reduces glycosylated hemoglobin levels, lactate dehydrogenase, and creatinine kinase in alloxan-treated mice. Ethanol extract of Syzygium leaves also improves TBARS oxidative stress parameters, catalase and superoxide dismutase activity and glutathione levels. The ethanol extract of Syzygium cumini leaves shows anti-diabetic activity through increased insulin secretion and this effect can be attributed to the content of flavonoids and phenolic compounds present in the ethanol extract of Syzygium cumini leaves.Abstrak : Penelitian ini dirancang untuk mengevaluasi aktivitas anti-diabetes dari ekstrak etanol daun Syzygium cumini (L) Skeels (EDS) pada mencit diabetes yang diinduksi aloksan. Aktivitas anti-diabetes EDS diselidiki pada mencit (Mus musculus SW.) diabetes yang diinduksi aloksan. Pengaruh ekstrak etanol daun Syzygium cumini (EDS) pada kadar glukosa darah normal dan uji toleransi glukosa oral dipelajari pada mencit normoglikemik sedangkan efek antidiabetik dievaluasi pada mencit hiperglikemik yang diinduksi aloksan. EDS (200 dan 400 mg/kg) diberikan secara oral selama 21 hari. Glibenclamide (5mg/kg, oral selama 21 hari) digunakan sebagai standar referensi. Pemberian EDS menyebabkan penurunan signifikan dalam kadar glukosa darah pada mencit normoglikemik dan hiperglikemik dan juga meningkatkan uji toleransi glukosa. EDS mengurangi kadar hemoglobin glikosilasi, laktat dehidrogenase, dan kreatinin kinase pada mencit yang diberi aloksan. EDS juga memperbaiki parameter stres oksidatif TBARS, aktivitas katalase dan superoksida dismutase dan kadar glutathione. Ekstrak etanol daun Syzygium cumini (EDS) menunjukkan aktivitas antidiabetik melalui peningkatan sekresi insulin dan efek ini dapat dikaitkan dengan kandungan flavonoid dan senyawa fenolik yang ada dalam ekstrak daun.

Abstract: Lactate dehydrogenase (LDH) is tumor prognostic for Non Hodgkin Lymphoma (NHL) and it levels would be elevated. The several papers has reported there are an association of total serum LDH levels and staging group of NHL. The study aimed to determine the differences of total serum LDH levels before and after the combination chemotherapy CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) for NHL’s patients at RSUD Ulin Banjarmasin during 3 years. It was an observational analyticstudy design and cross-sectional approach, data collected with design method of totally sampling. Of the 51 patient medical records who included, 54,9% were staging group I-II and 45,1% were staging group III-IV. The first statistic analytic used dependent T test with p=0,303 (p>0,05)showed no differencesof total serum LDH levels before and after the combination chemotherapy CHOP in NHL’s patients with staging group I-II. The second statistic analytic used alternative wilcoxon test with p=0,013 (p<0,05) showed differencesof total serum LDH levels before and after the combination chemotherapy CHOP in NHL’s patients with staging groupIII-IV. The third statistic analytic used alternative mann whitney test with p=0,161 (p>0,05) showed no differencesof total serum LDH levels after the combination chemotherapy CHOP in NHL’s patients between staging group I-II and III-IV.Keywords: total serum LDH levels, NHL, combination chemotherapy CHOP Abstrak: Laktat dehidrogenase (LDH) adalah tumor prognostic pada kanker Limfoma Non Hodgkin (LNH) dan kadarnya selalu menunjukan peningkatan. Penelitian sebelumnya melaporkan bahwa terdapat hubungan antara kadar LDH serum total dengan kelompok stadium kanker LNH. Penelitian ini bertujuan untuk mengetahui perbedaan kadar LDH serum total sebelum dan sesudah kemoterapi kombinasi CHOP (Siklofosfamid, Doksorubisin, Vinkristin, dan Prednison) pada penderita kanker LNH di RSUD Ulin Banjarmasin selama 3 tahun.Penelitian ini menggunakan rancangan studi observasional analitik dan metode pendekatan cross sectional, pengambilan sampel dengan teknik rancangan totally sampling. Dari 51 data rekam medik yang termasuk kriteria inklusi, 54,9% kelompok stadium I-II dan 45,1% kelompok stadium III-IV. Analisis statistik pertama menggunakan uji T berpasangandengan p=0,303 (p>0,05) sehingga tidak terdapat perbedaan kadar LDH serum total sebelum dan sesudah kemoterapi kombinasi CHOP pada penderita kanker LNH kelompok stadium I-II. Analisis statistik kedua menggunakan uji alternatif yaitu uji wilcoxondengan p=0,013 (p<0,05) sehingga terdapat perbedaan kadar LDH serum total sebelum dan sesudah kemoterapi kombinasi CHOP pada penderita kanker LNH kelompok stadium III-IV. Analisis statistik ketiga menggunakan uji alternatif yaitu uji mann whitney dengan p=0,161 (p>0,05) sehingga tidak terdapat perbedaan kadar LDH serum total sesudah kemoterapi kombinasi CHOP pada penderita kanker LNH antara kelompok stadium I-II dan III-IV. Kata-kata kunci: kadar LDH serum total, LNH, kemoterapi kombinasi CHOP

Perbandingan struktur primer L(+)–mendalate dehydrogenase (L–MDH) daripada yis Rhodotorula graminis dengan protein lain di dalam bank data protein menunjukkan persamaan di antara protein ini dengan kumpulan enzim L–2–hidroksiasid dehidrogenase. LMDH daripada R. graminis mempamerkan kesamaan antara 26–42% kepada L–lactate dehidrogenase daripada Sacchomoryces cerevisiae, L–lactate dehidrogenase daripada Hansenula anomala, glikolat oksida daripada bayam, L–laktat dehidrogenase daripada Escherichia coli, LMDH daripada Psedomonas putida dan laktat–2 monooksigenase daripada Mycobakterium smegmatis. Asid amino yang penting secara strukturnya bagi LMDH diramalkan secara perbandingan dengan bahagian penting domain sitokram dan domain perlekatan FMN yang diperoleh daripada struktur tiga dimensi L–laktat dehidrogenase daripada Sacchoromyces cerevisiae. Kata kunci: L-MDH; Rhodotorula gramisis; L(+)-mandalate dehydrogenase; asid amino,flavocytochrome b2 A comparison of the primary structure or L–mandelate dehydrogenase (L–MDH) from Rhodotorula graminis with other proteins from the protein databank suggests that there is similarity between this protein and L–2–hydroxyacid dehydrogenase enzymes. R graminis LMDH exhibits 26–42% identity to L–lactate dehydrogenase from Saccharomyces cerevisiae, L–lactate dehydrogenase from Hansenula anomala, glycolate oxidase from spinach, L–lactate dehydrogenase from Escherichia coli, L–mandelate dehydrogenase from Pseudomonas putida and lactate–2–monooxygenase from Mycobacterium smegmatis. Structurally conserved amino acids are predicted from LMDH sequences corresponding to important regions of the cytochrome and FMN–binding domain defined from the known three–dimensional structure of the L–lactate dehyrogenase from Sacchoromyces cerevisiae. Key words: L-MDH; Rhodotorula graminis; L-mandelate dehydrogenase; amino acid;flavocytochrome b2

AbstrakAwal abad ke-2l masyarakat Indonesia mengalami transisi epidemiologi penyakit. Perubahan pola penyakit ini dapat dilihat dari peningkatan insiden penyakit kanker sebagai penyebab kematian di Indonesia dalam 10 tahun terakhir, yaitu dari urutan ke-12 menjadi urutan ke-6. Di Indonesia, limfoma non Hodgkin (LNH) menduduki urutan keenam keganansan yang sering terjadi. Berdasarkan penelitian yang dilakukan oleh Olivia Putri Perdana di bagian patologi anatomi Fakultas Kedokteran Universitas Andalas didapatkan data bahwa pada januari 1997-desember 2001 terdapat 70 (81,39%) penderita limfoma maligna non Hodgkin dari keseluruhan penderita limfoma maligna. Penelitian ini bertujuan untuk mengetahui hubungan kadar laktat dehidrogenase (LDH) dengan stadium pada penderita limfoma maligna non Hodgkin. Penelitian ini adalah penelitian analitik dengan pendekatan cross sectional dengan menggunakan data yang bersumber dari rekam medik pasien. Populasi dari penelitian ini adalah data rekam medik seluruh penderita limfoma maligna non hodgkin yang berobat ke RSUP Dr. M. Djamil Padang yaitu 317 data rekam medik, tetapi yang memenuhi syarat untuk menjadi sampel hanya 40 data. Analisis statistik yang digunakan adalah uji T. Hasil uji statistik menunjukkan adanya hubungan kadar laktat dehidrogenase dengan stadium pada penderita limfoma non Hodgkin (P = 0,001). Diketahui nilai laktat dehidrogenase pada stadium III-IV lebih tinggi daripada nilai laktat dehidrogenase pada stadium I-II.Kata kunci: Laktat dehidrogenase, Limfoma maligna non Hodgkin, Stadium AbstractEarly 21th century, Indonesian society in transition epidemiology of the disease. Changing patterns of disease can be seen from the increased incidence of cancer as a cause of death in Indonesia in the last 10 years, ie from 12th to 6th order. In Indonesia, non-Hodgkin's lymphoma (NHL) ranks sixt frequent in all of cancer. Based on research conducted by Olivia Putri Perdana in anatomic pathology at the Faculty of Medicine, University of Andalas that the data obtained during the January 1997 - December 2001 there were 70 (81.39%) patients with non -Hodgkin's malignant lymphoma of the overall malignant lymphoma patients.This study aims to determine the relationship of levels of lactate dehydrogenase (LDH) with stage of non -Hodgkin's malignant lymphoma patients.This research is a cross sectional analytic approach using data derived from patient medical records. The population is the entire medical record malignant non Hodgkin lymphoma patients who went to DR. M. Djamil Padang hospital, they are 317 medical records, but are eligible to be sampled only 40 data. Statistical analysis used is the T test.Statistical test results show that there is relationship between lactate dehydrogenase levels with stage in non -Hodgkin's lymphoma patients (P = 0.001). Known value of lactate dehydrogenase in stage III - IV is higher than the value of lactate dehidrodenase in stage I - II.Keywords: Lactate dehydrogenase, malignant non-Hodgkin's lymphoma, Stage

Die von Tumorzellen exzessiv exprimierte Laktat-Dehydrogenase 5 (LDH-A) ist das Schlüssel-Enzym für den katalytischen Stoffwechsel um Pyruvat in Laktat unter Gewinnung von Energie umzuwandeln. Bei LDH handelt es sich um einen wichtigen prognostischen Marker für die Einstufung der Aggressivität und die Behandlung von Tumoren. Ziel dieser Arbeit war es, das Wissen um die Funktion des Genproduktes von LDH-A (LDH-V) in Bezug auf die Proliferation von Tumorzellen, die Expression Angiogenese-Gene, maligne Konversion von Tumoren und die Metastasierung zu vertiefen. Zusätzlich sollte die Rolle von LDH auf die Genexpression HIF-regulierter Proteine, die das Überleben von Tumorzellen und vor allem der Glykolyse fördern, untersucht werden. Hierfür wurden LDH-A knockdown-Klone von dem murinen B16F10 Melanom und Lewis Lung Karzinom sowie dem humanem HT29 Kolonkarzinom generiert und in vitro und in vivo in den drei verschiedenen Tumormodellen untersucht. Der knockdown von LDH-A führte in vitro zu einer Hemmung der Proliferation in Lewis Lung und B16F10, während bei HT29 Tumorzellen kein solcher Effekt beobachtet werden konnte. Interessanterweise ließen sich nicht bei allen drei Zelllinien die durch limitierte LDH Aktivität ausgelösten Effekte auf die in vitro Proliferation auf das Tumorwachstum in vivo übertragen: Das Wachstum der Lewis Lung als auch der HT29 Tumoren in vivo war durch die Reduktion von LDH-A drastisch vermindert, während die Größe der B16F10 Tumoren davon nicht beeinflusst war. Es konnte gezeigt werden, dass B16F10 Tumoren unter LDH Suppression verstärkt VEGF exprimieren. Dadurch waren diese Zellen in vivo in der Lage, durch verstärkte Vaskularisierung des Tumors der durch LDH-A knockdown ausgelösten Hemmung des Tumorwachstums zu entkommen. Bei Lewis Lung Tumorzellen hingegen, führte die Unterdrückung von LDH-V zu einer beeinträchtigten Glukoseaufnahme unter normoxischen sowie hypoxischen Bedingungen. Die reduzierte Aufnahme von Glukose hatte in vivo, in einer vielschichtigen komplexen Struktur, deutlich größere Auswirkungen als auf einer eindimensionalen Zellkulturschale. Die Ergebnisse der vorliegenden Arbeit liefern neue Erkenntnisse zur Rolle von LDH-V während der Tumorprogression und können als Grundlage für zukünftige, neue Therapiestrategien bei Krebspatienten dienen.
LDH is an important prognostic marker in cancer staging and therapy. High serum LDH activity is associated with poor patient prognosis in different tumor types. LDH-A has been shown to play a major role in tumor malignancy, but the molecular mechanism behind this role is only starting to be understood. The objective of this work was to broaden our knowledge about the role of LDH-A gene product (LDH-V) in tumor cell proliferation, angiogenesis-related gene expression, tumor malignancy and metastasis. Herein, LDH-A shRNA knockdown clones of murine B16F10 melanoma, Lewis Lung carcinoma and human HT29 colon carcinoma were generated to uncover the molecular mechanisms between diminished ability of metabolizing pyruvate to lactate and tumor cell growth in vitro and in vivo. In this study, a significant correlation between tumor weight and serum LDH in in vivo tumor models was found, which additionally correlated with the in vitro LDH secretion. In vitro, suppression of LDH-A led to anti-proliferative effects in Lewis Lung and B16F10 tumor cells, while having no effect on HT29 cells. Interestingly, the consequence of limiting LDH activity in vitro did not show a direct correlation to the in vivo anti-tumor effects in LDH-deficient tumors: B16F10 tumor growth was unaffected by silencing LDH-A, while Lewis Lung and HT29 demonstrated a drastic reduction in tumor growth in vivo. B16F10 tumors were found to have increased VEGF expression upon LDH knockdown, and therefore were able to compensate the tumor growth inhibition-driven by LDH deficiency through increased tumor vascularization in vivo. In contrast, LDH-V suppressed Lewis Lung cells demonstrated an impeded glucose uptake ability under normoxic and hypoxic conditions. Subsequently, a genome-wide gene expression analysis and functional assays of LDH-A deficient and control HT29 clones revealed potential new oncogenic features of LDH-A in tumor migration and invasion as well as a feedback loop to HIF1alpha. In summary, the collective data presented in this thesis provide new insights of LDH-V in tumor progression and therapeutic strategies for the treatment of cancer.

Kardijalni biomarkeri u predviđanju operativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore Evaluacija rezultata u kardiohirurgiji podrazumeva praćenje ishoda operativnog lečenja u određenom vremenskom periodu. Najčešće je to interval od 30 dana od datuma intervencije. Najčešći kriterijumi za praćenje su stopa mortaliteta i morbiditeta, dužina boravka u jedinici intenzivnog lečenja, ukupna dužina hospitalizacije i troškovi lečenja. Stratifikacija rizika podrazumeva da se bolesnici mogu podeliti u grupe u zavisnosti od broja i važnosti preoperativno utvrđenih faktora rizika, odnosno da se pre operacije može predvideti ishod hirurške intervencije kod svakog od njih pojedinačno. U Evropi je, u periodu između 1995. i 1999. godine, na osnovu multicentrične studije u 8 evropskih zemalja i 128 kardiohirurških centara u kojima je operisano 19.030 odraslih bolesnika, kreiran EvroSKOR - EuroSCORE (European System for Cardiac Operative Risk Evaluation) model za stratifikaciju rizika u kardiohirurgiji. Međutim, neminovne promene i napredak u operativnom lečenju doveli su do toga da je neophodno ažurirati postojeći sistem stratifikacije. Tako je 2012. godine u rutinsku upotrebu uveden novi sistem Euroscore II. Na Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV), EuroSCORE model uveden je u rutinsku upotrebu od početka 2001. godine. Analizom rezultata, posle dvogodišnje primene, pokazalo se da je model bio precizan, odnosno da nije postojala značajna razlika između očekivanog (3,7%) i stvarnog mortaliteta (3,47%). U poslednjih nekoliko godina, kod bolesnika kojima sledi kardiohirurška intervencija, u smislu razmatranja njihove prediktivne vrednosti, sve više pažnje se poklanja kardijalnim biomarkerima. Najznačajniji biomarkeri u kardiovaskularnoj medicini su: Troponin, Kreatin kinaza MB izoenzim (CKMB), N-terminalni pro B-tip natriuretski peptid (NT-proBNP), C-reaktivni protein (CRP), Laktat dehidrogenaza (LDH), Mokraćna kiselina (Acidum uricum). Ciljevi ovog rada su bili da se kreira model za predviđanje preoperativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore na osnovu preoperativnih vrednosti određenih biomarkera i da se kreira novi model sa kombinacijom prethodnog modela i već postojećeg modela EuroSCORE II. Ispitana su 704 bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcione frakcije manje ili jednake 50%. Bolesnici su operisani na Institutu za kardiovaskularne bolesti Vojvodine, od 20. januara 2014. do 20. aprila 2016. Kod bolesnika su urađene tri vrste operacija: revaskularizacija miokarda-koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije. Od biohemijskih analiza, 24 sata pre operacije, urađene su sledeće analize: troponin I, kreatin kinaza, kreatin kinaza MB izoenzim, masena kreatin kinaza, laktat dehidrogenaza, C-reaktivni protein, NT-proBNP i mokraćna kiselina. Praćen je postoperativni mortalitet, postoperativni infarkt miokarda i postoperativni cerebrovaskularni incident i njihova povezanost sa preoperativnim vrednostima nabrojanih biomarkera. U studiju su bili uključeni svi bolesnici sa stečenim bolestima srca, stariji od 18 godina, kod kojih je ejekciona frakcija leve komore bila manja ili jednaka 50% i kod kojih su izvršene sledeće vrste operacija: revaskularizacija miokarda - koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije - koronarna i valvularna hirurgija. Rezultati su pokazali da je postoperativni mortalitet bio 3,13%, da je postoperativni infarkt miokarda imalo 7,95% a postoperativni cerebrovaskularni incident 9,23% od ukupnog broja ispitanika. 1. Povezanost vrednosti biomarkera sa postoperativnim infarktom miokarda kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I su bile povezane sa postoperativnim infarktom miokarda. Povezanost preoperativnih vrednosti biomarkera sa postoperativnim cerebrovaskularnim incidentom kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I i CRP-a su bile povezane sa postoperativnim cerebrovaskularnim incidentom. 2. Analiziran je uticaj preoperativnog nivoa svih biomarkera, pojedinačno, na značajne neželjene kardijalne i cerebrovaskularne događaje - Major Adverse Cardiac and Cerebrovascular Events (MACCE) kao ishod posle operacije na srcu, kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore. Dobijeni su sledeći rezultati: Preoperativna vrednost nivoa troponina I veća od 0,01μg/L i MACCE bili su povezani. Povećane preoperativne vrednosti nivoa C-reaktivnog proteina (CRP) i postoperativni MACCE bili su povezani. Povećane preoperativne vrednosti nivoa laktat dehidrogenaze (LDH) i MACCE bili su povezani. Zaključci ove teze su: 1. Nezavisni prediktor postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, jeste povišena preoperativna vrednost troponina I. 2.Vrednost preoperativnog troponina I je slab marker za predviđanje postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 3. Na pojavu postoperativnog cerebrovaskularnog incidenta, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, ne utiče nijedna od ispitivanih varijabli. 4. Nezavisni prediktori postoperativnog mortaliteta kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, na osnovu kojih je moguće kreirati prediktivni Model su godine starosti i povišene preoperativne vrednosti NT-proBNP. 5. Kreirani Model je dobar marker za predikciju ishoda posle operacije na srcu, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 6. Povišena preoperativna vrednost NT- proBNP može da bude dobar marker u predikciji smrtnog ishoda posle operacije na srcu kod bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 7. Model EuroSCORE II se pokazao kao slabiji marker za predikciju ishoda posle operacije na srcu kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 8. Testiranjem kreiranog modela, podelom na manje rizične i više rizične bolesnike, u odnosu na visinu ejekcione frakcije leve komore, pokazalo se da je model dobar marker za predviđanje smrtnog ishoda posle operacije na srcu, u obe grupe.
Cardiac surgery operative risk assessment in patients with imapired systolic left ventricular function using cardial biomarkers Evaluation of results in cardiac surgery involves monitoring the outcomes of operative treatment in a given time period. Typically, this interval includes 30 days from the date of operation. The most common criteria used for monitoring are the rate of mortality and morbidity, length of stay in the intensive care unit, the total length of hospitalization and medical costs. Risk stratification means that patients can be divided into groups depending on the number and importance of preoperatively identified risk factors, and that the outcome of surgery for each of the patients can be predicted preoperatively. In Europe, in the period of 1995-1999 on the basis of a multi-center study in 8 European countries and 128 cardiac centers in which 19,030 adult patients were operated on, EuroSCORE (European System for Cardiac Operative Risk Evaluation) model for risk stratification in cardiac surgery was developed. However, the inevitable changes and progress in the surgical treatment rendered the EuroSCORE model obsolete warranting updated system. It was in 2012 when a new system EuroSCORE II was introduced into practice At the Clinic for Cardiac Surgery of the Institute of Cardiovascular Diseases, EuroSCORE model was introduced in routine clinical use since the beginning of 2001. By analyzing the results, two years after application, it was shown that the model was accurate, and that there was no significant difference between the expected (3.7%) and the actual mortality (3.47%) In recent years, in patients who are candidates for cardiac surgery, more attention is paid to cardiac biomarkers in terms of evaluating their predictive power. The most significant biomarkers in cardiovascular medicine are: Troponin, creatine kinase MB isoenzyme (CKMB), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), Lactate dehydrogenase (LDH), and uric acid (Uric uricum). The objectives of this study were to create a model to predict preoperative risk for cardiac surgery patients with impaired systolic left ventricular function on the basis of preoperative levels of certain biomarkers and to create a new model with a combination of the previous model and already existing EuroSCORE II model. The study included 704 patients with impaired systolic left ventricular function, ejection fraction less than or equal to 50%. All patients underwent cardiac surgery at the Institute of Cardiovascular Diseases, from January 20th 2014 until 20th April 2016. Patients were submitted to three types of operations: revascularization - coronary surgery, surgery of acquired heart defects - valvular surgery and combined operations. Following biochemical analyses were performed 24 hours prior to surgery: troponin I, creatine kinase, creatine kinase MB isoenzyme, mass creatine kinase, lactate dehydrogenase, C-reactive protein, NT-proBNP and uric acid. Postoperative mortality, postoperative onset of myocardial infarction and occurence of cerebrovascular accident and their correlation with preoperative values of listed biomarkers were registered. The study included all patients with acquired heart disease, older than 18 years, with the left ventricular ejection fraction less than or equal to 50% who were submitted to the following types of operations: revascularization - coronary surgery, surgery of acquired heart diseases - valvular surgery and combined operations - coronary and valvular surgery. The results showed that the postoperative mortality was 3.13%, new onset of postoperative myocardial infarction was detected in 7.95% of the patients and postoperative cerebrovascular accident developed in 9.23% of patients. Correlation of preoperative biomarkers values with postoperative myocardial infarction in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I were associated with postoperative myocardial infarction. Correlation of preoperative biomarkers values with postoperative cerebrovascular incident occurence in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I and CRP were associated with postoperative cerebrovascular incident. The influence of preoperative levels of all biomarkers, separetly, on the rate of significant adverse cardiac and cerebrovascular events - Major Adverse Cardiac and Cerebrovascular Events (MACCE) as the heart surgery outcome, in patients with impaired left ventricular ejection fraction. The following results were obtained: Increased preoperative levels of C-reactive protein (CRP) and postoperative MACCE were related. Increased preoperative levels of lactate dehydrogenase (LDH) and MACCE were related. The conclusions of this thesis are: 1. Independent predictor of postoperative myocardial infarction onset and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%) is elevated preoperative value of troponin I. 2. Preoperative Troponin I value was poor marker for predicting postoperative myocardial infarction and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 3. None of the studied variables showed influence on the postoperative cerebrovascular accident occurence, in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 4. Independent predictors of postoperative mortality in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%), that could be used to create a predictive model are: age and elevated preoperative value of NT-proBNP. 5. Developed model showed satisfactory results for predicting outcome after heart surgery in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 6. Elevated preoperative value of NT-proBNP may be a good marker for mortality prediction after the cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 7. EuroSCORE II model showed poor performance when predicting outcomes after cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 8. Validation of the newly-created model, considering low and medium risk patients, based on the value of left ventricular ejection fraction, showed that the model is a good marker for the mortality prediction in both groups.

Die genaue physiologische Funktion des zellulären Prion-Proteins (PrPC) ist noch immer nicht vollständig verstanden. Eine mögliche Funktion des PrPC auf das neuronale Überleben nach einem hypoxischen oder ischämischen Insult wird diskutiert. In einem Vorversuch zeigten sich nach zerebraler Ischämie deutlich größere Infarktvolumina in den Gehirnen von Prion-Knock-Out-Mäusen im Vergleich zu denen der Wild-Typ-Mäuse. Das Identifizieren der molekularen Mechanismen der PrPC-vermittelten Neuroprotektion ist daher von großem Interesse und machte die Etablierung eines Zell-Modells erforderlich. Neuere Studien konnten einen Einfluss des zellulären Prion-Proteins auf die Glykolyse nachweisen. Unter Sauerstoffmangelbedingungen kommt es zu einer vermehrten Bildung von Laktat durch das Enzym Laktat-Dehydrogenase (LDH). Neurone benötigen unter hypoxischen oder ischämischen Bedingungen dieses Laktat als Energiesubstrat. Je mehr Laktat den Neuronen zur Verfügung steht, umso höher ist das neuronale Überleben. In dieser Arbeit konnte die Beteiligung der Laktat-Dehydrogenase an der durch das zelluläre Prion-Protein vermittelten Neuroprotektion nach Hypoxie nachgewiesen werden. Das Ziel dieser Arbeit bestand darin, mögliche Unterschiede der LDH-Expression in WT-Zellen, Prnp0/0-Zellen und HEK-293-Zellen unter normalen und hypoxischen Bedingungen in vitro zu untersuchen. Die Expression der LDH war unter hypoxischen Bedingungen in den WT-Zellen im Vergleich zu den Prnp0/0-Zellen deutlich höher. Dies konnte auch in PrPC-überexprimierenden HEK-293-Zellen nach Hypoxie gezeigt werden. Ebenso konnte nachgewiesen werden, dass Hypoxie zu einem größeren Schaden des Tubulinzytoskelettes in Prnp0/0-Zellen führt als in WT-Zellen, was eine neuroprotektive Wirkung von PrPC vermuten lässt. Eine direkte oder indirekte Interaktion von LDH-A und PrPC konnte durch eine Co-Immunpräzipitation in HEK-293-Zellen nachgewiesen werden. Die genauen Mechanismen über die PrPC möglicherweise zu einer vermehrten Laktat-Produktion führt, sind noch nicht eindeutig identifiziert und müssen noch näher untersucht werden. Zusammengefasst kann gesagt werden, dass die erhobenen Daten die Vermutung verstärken, dass das Enzym LDH und sein Produkt Laktat in die durch das zelluläre Prion-Protein vermittelte Neuroprotektion nach Hypoxie involviert sind. Es ist das erste Mal, dass gezeigt wurde, durch welchen Mechanismus PrPC zur Neuroprotektion beiträgt.

Adaptation to hypoxia is a well-known phenomenon increasing myocardial resistance to ischemia-reperfusion (I/R) injury as an appropriate physical exercise which improves the contractile function of the heart. Lactate is a major energy substrate for the heart muscle during physical activity and hypoxia. The metabolism of lactate was and still is associated with muscle fatigue, but in the last decades it has been considered its significant modulating function of metabolism during exercise at cellular level and whole organism level. It has been shown that its effects might be similar to the effects of hypoxia and its oxidized form, pyruvate, has the cardioprotective effects. The aim of this study was to compare the expression of LDHA and LDHB isoforms between left and right ventricle in the cardioprotective scheme of adaptation to hypoxia. Another objective/goal was to determine the left ventricular response to I/R insult in the perfused heart model adapted to hypoxia compared with the normoxic controls on/at the expression level of both LDH isoforms. Our results showed differences in the LDHA expression in the left and right ventricle and an increased response of the left ventricle to I/R insult in rats adapted to hypoxia which is reflected at the expression level of both isoforms. Key words: heart,...