Mark Mazower (ed.), Networks of Power in Modern Greece: Essays in Honour of John Campbell

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Χρήση του φυτού Arabidopsis Thaliana ως μοντέλο για την απόκριση σε βλάβες DNA, έπειτα από έκθεση σε Ιοντίζουσα Ακτινοβολία, με χρήση δεδομένων μικροσυστοιχιών.

Είναι γνωστό ότι η έκθεση βιολογικών ιστών σε ιοντίζουσες ακτινοβολίες (IR) έχει ως αποτέλεσμα την επαγωγή μιας σειράς μηχανισμών ως απόκριση στις βλάβες που δημιουργούνται στο DNA, γνωστοί και ως DNA Damage Response (DDR). Σκοπός της παρούσας διπλωματικής είναι η διερεύνηση των μηχανισμών αυτών στην περίπτωση του φυτού μοντέλου Arabidopsis Thaliana. Η προσέγγιση που επιλέχθηκε ήταν η ανάλυση διαφορικής έκφρασης (Differential Gene Expression Analysis - DGEA) βασισμένη σε δεδομένα μικροσυστοιχιών από δημόσια αποθετήρια. Η αναζήτηση των πειραματικών μας δεδομένων έγινε στη βάση ArrayExpress, καταλήγοντας σε ένα μόνο dataset με κωδικό E-GEOD-61484. Τα δείγματα του νεαρού βλαστού της A. Thaliana είχαν εκτεθεί σε 100Gy ακτινοβολίας-γ ή 30Gy ακτινοβολίας HZE. Οι χρόνοι συλλογής των δειγμάτων έπειτα από ακτινοβόληση ήταν στις 1.5, 3, 6, 12, 24 ώρες. Τα στατιστικώς σημαντικά διαφορικώς εκφρασμένα γονίδια αναδείχθηκαν με χρήση της γλώσσας R. Το σύνολο των διαφορικώς εκφραζόμενων γονιδίων που προκύπτει, γνωστά ως DEGs, χρησιμοποιήθηκε για τη δημιουργία δικτύων πρωτεϊνικών αλληλεπιδράσεων μέσω της STRING για τα δύο είδη ακτινοβολίας ξεχωριστά καθώς επίσης για τη διεξαγωγή ανάλυσης εμπλουτισμού (enrichment analysis) σχετικά με βιολογικές διεργασίες της GO (Gene Ontology). Τέλος, έπειτα από επιλογή των σημαντικών DEGs χρησιμοποιήθηκε το εργαλείο DIOPT για την ανάδειξη των αντιστοίχων ορθολόγων στον άνθρωπο. Τα αποτελέσματα μας υποδεικνύουν ενεργοποίηση γνωστών μηχανισμών DDR και για τα δύο είδη ακτινοβολίας, όπως σημεία ελέγχου του κυτταρικού κύκλου, επιδιορθωτικών μηχανισμών DNA και μηχανισμών γήρανσης. Παρόλα αυτά, μηχανισμοί απόπτωσης εμφανίζονται μόνο στην περίπτωση έκθεσης σε HZE. Επιπλέον βασικές διαφορές στην περίπτωση των HZE είναι η έντονη ενεργοποίηση του έμφυτου ανοσοποιητικού και της αυτοφαγίας. Κάτι ακόμη που παρατηρείται είναι η τάση του κυττάρου να επανέρχεται στη φυσιολογική του κατάσταση 24 ώρες μετά την ακτινοβόληση. Τέλος, από την αναζήτηση ζευγών ορθολόγων μεταξύ φυτού και ανθρώπου προκύπτει η έντονη συσχέτιση με μηχανισμούς DDR στον άνθρωπο, γεγονός που καθιστά την A. thaliana ως ικανοποιητικό μοντέλο για την μελέτη των επιδράσεων IR.It is known that the exposure of biological tissues to ionizing radiation (IR) results in the induction of a series of mechanisms as a response to DNA damage, known as DNA Damage Response DDR. The aim of this master thesis is the investigation of these mechanisms in the model organism Arabidopsis Thaliana. Our selected approach was Differential Gene Expression Analysis (DGEA) based on microarray data from public repositories. The search for our experimental data was conducted in the ArrayExpress database, resulting in only one dataset with accession code E-GEOD-61484. The samples of Arabidopsis Thaliana seedlings were exposed to 100Gy gamma or 30Gy HZE radiation. They were collected across a range of time points 1.5, 3, 6, 12, 24 hours respectively. The statistically significantly differentially expressed genes emerged through the use of R programming language. The total number of differentially expressed genes, known as DEGs, were used for the creation of protein-protein interaction networks. To this end, we utilized STRING database for both ionizing radiation types. The same DEG lists were used for performing a functional enrichment analysis concerning biological processes of GO (Gene Ontology). In the final step of our analysis, we opted for DEGs involved in main processes to predict pairs of orthologs between plant and human through the DIOPT tool. Our results indicate activation of common DDR mechanisms for both radiation types, such as cell cycle check points, DNA repair and aging mechanisms. Nonetheless, the phenomenon of apoptosis is appeared in the case of HZE exposure. Additionally in the same case, the main differences observed in our enrichment analysis results were the intense activation of innate immune system as well as the induction of autophagy. We also observed was the tendency of cell to obtain its homeostasis 24 hours after exposure to HZE. Finally, a strong correlation concerning DDR mechanisms emerged from the predicted pairs of orthologs, verify A. thaliana as acceptable model organism for studying the effects of IR

Influence of hematocrit on hemostasis in continuous venovenous hemofiltration during acute renal failure

Influence of hematocrit on hemostasis in continuous venovenous hemofiltration during acute renal failure.BackgroundHematocrit plays a major role in primary hemostasis by influencing blood viscosity and platelet adhesion. During continuous venovenous hemofiltration (CVVH), it is suspected that an increased hematocrit is accompanied by an activation of hemostasis and frequently leads to thromboses in the extracorporeal system. In order to examine this hypothesis, we studied the influence of hematocrit on hemostasis during CVVH.MethodsFourteen patients (8 men and 6 women, mean age 65 ± 10 years) with acute renal failure undergoing CVVH were prospectively enrolled. Polysulfone hemofilters (AV 600®; Fresenius, Oberursel, Germany) were used in all of the patients; blood flow rates were adjusted to 120 ml/min. No blood products and coagulation-related medication, except unfractionated heparin, were applied. Study exclusion criteria included a history of thromboembolism and artificial heart valves. Hemostasis activation markers (fibrinopeptide A, thrombin-antithrombin III complex, β-thromboglobulin, platelet retention) and hematocrit values were determined before and at three-day intervals during the course of CVVH treatment.ResultsThe mean hematocrit value ( ± sem) was 29 ± 1% (range, 22 to 35%). Patients with hematocrit values of less than 30% (N = 7) were compared with patients with higher hematocrit values (>30%, N = 7). The patients with a lower hematocrit (<30%) showed a stronger activation of hemostasis during CVVH when compared with those with a higher hematocrit (>30%), as indicated by a tendency toward higher values for fibrinopeptide A (25 ± 8 vs. 14 ± 5 ng/ml, P = 0.35), thrombin-antithrombin III complex (15 ± 4 vs. 10 ± 2 ng/ml, P = 0.66), and a higher β-thromboglobulin/creatinine ratio (0.62 ± 0.17 vs. 0.48 ± 0.12, P = 0.8).ConclusionContrary to our hypothesis, hematocrit values of more than 30% are not accompanied by an increased hemostasis activation during CVVH. Concerning hemostasis activation, hematocrit values between 30 and 35% may be suitable for patients on CVVH

Postpartal recurrent non-ST elevation myocardial infarction in essential thrombocythaemia: case report and review of the literature

Normal pregnancy corresponds to a procoagulant state. Acute myocardial infarction during pregnancy is rare, yet considering the low non-pregnant risk score of childbearing women it is still surprisingly frequent. We report a case of postpartum recurrent non-ST elevation myocardial infarction in a 40-year-old caucasian woman with essential thrombocythaemia in the presence of a positive JAK-2 mutation and an elevated anti-cardiolipin IgM antibody titer. In the majority of cases of myocardial infarction in pregnancy or in the peripartal period, atherosclerosis, a thrombus or coronary artery dissection is observed. The combination of essential thrombocythaemia and elevated anti-cardiolipin IgM antibody titer in the presence of several cardiovascular risk factors seems to be causative in our case. In conclusion, with the continuing trend of childbearing at older ages, rare or unlikely conditions leading to severe events such as myocardial infarction must be considered in pregnant women

Restless legs syndrome/Willis–Ekbom disease prevalence in beta thalassemia patients

Purpose Both beta thalassemia and restless legs syndrome (RLS) patients share some common pathophysiological characteristics related to iron handling. In the present study, the aim was to explore the prevalence of RLS as well as to explore potential association between the syndrome and various quality of life-related parameters in a sample of beta thalassemia patients. Methods One hundred fourteen (age 40 ± 11 yr, 59 M/55F) beta thalassemia patients participated in this cross-sectional descriptive study. Patients were screened for RLS based on the international RLS study group diagnostic criteria as well as a battery of validated questionnaires. Results The prevalence of RLS in this sample of beta thalassemia patients was zero. The quality of life score was low (78 ± 18). Iron levels were within normal range (191 ± 66 mcg/dL) while ferritin levels were high as expected (1836 ± 225 ng/dL). Conclusions Our sample of patients comes from central Greece where the prevalence of RLS in the general population is 4% while in renal failure patients is 27%. To our surprise, there was no presence of RLS among this sample of beta thalassemia patients. The adequate levels of iron and ferritin often seen in these patients could be the reason of the absence of RLS symptoms

Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review.

Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD

Restless legs syndrome is contributing to fatigue and low quality of life levels in hemodialysis patients

AIM: To examine whether hemodialysis (HD) patients with restless legs syndrome (RLS) are subjects of greater fatigue and impaired quality of life (QoL) compared to HD patients without RLS. METHODS: Eighty five stable HD patients participated in this study. According to their RLS status, the patients were divided into the RLS group (n = 23) and the non-RLS group (n = 62). QoL, fatigue, sleep quality, daily sleepiness and depression symptoms were assessed by using various questionnaires. Finally, biochemical parameters including iron, ferritin, hemoglobin, hematocrit and parathormone were assessed. RESULTS: The HD patients with RLS scored worse in all the questionnaires used in the study (P < 0.05). The patients with RLS were more likely to receive the HD therapy on the morning shift, whilst 43.5% of the RLS patients reported to experience the RLS symptoms also during HD. The severity of RLS was correlated with fatigue, depression score and sleep quality (P < 0.05). CONCLUSION: HD patients with RLS are subject to lower QoL related parameters and greater fatigue compared to HD patients without RLS. RLS should be successfully managed in order to improve the QoL of the sufferers