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

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

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

Phosphorus nutritional knowledge among dialysis health care providers and patients: a multicenter observational study

Background-aims Phosphorus nutritional knowledge level of hemodialysis patients and renal nurses has been found to be low, while respective knowledge of nephrologists has not been studied yet. There are equivocal results regarding the association of phosphorus nutritional knowledge level and serum phosphorus values. The aim of this study was to assess phosphorus nutritional knowledge of hemodialysis patients, nephrologists and renal nurses and seek potential interventions to improve patients’ adherence to phosphorus and overall nutritional guidelines. Methods This cross-sectional observational study was conducted on sixty eight hemodialysis patients, 19 renal nurses and 11 nephrologists who were recruited from 3 hemodialysis units in Greece. Phosphorus nutritional knowledge of the participants was assessed by a 25-item item questionnaire (CKDKAT–N) which included 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge. Results Nephrologists had higher CKDKAT–N total (19.1 ± 3.6 vs 14.1 ± 2.8 and 13.2 ± 2.8, P < 0.01) and phosphorus knowledge scores (10.6 ± 2.7 vs 7.6 ± 2.2 and 7.3 ± 2.0, P < 0.01) compared to renal nurses and patients respectively. There were no differences in total and phosphorus knowledge scores between nurses and patients. Patients and nurses answered correctly significantly less questions regarding phosphorus compared with the rest of the questions (P < 0.01) while no such difference was found in nephrologists. Serum phosphorus was positively correlated with phosphorus knowledge score (r = 0.31, P = 0.02), and negatively correlated with patient age (r = −0.34, P < 0.05). None of the patients, 11% of the nurses and 27% of the nephrologists answered correctly all three questions regarding P, K and Na dietary recommendations (P < 0.01). Conclusions The study confirms that hemodialysis patients have low renal nutrition knowledge while higher nutritional phosphorus knowledge does not lead to lower serum phosphorus values. Alarmingly, renal nurses have been found to have a similar level of knowledge with hemodialysis patients, something that needs to be taken into account when training the new dialysis staff. Nephrologists have superior knowledge; however they are still lacking essential nutritional knowledge that could affect patients' and nurses’ overall understanding. Continuing education on nutrition of nephrologists and renal nurses could improve nutrition care of hemodialysis patients

MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease

Background: Restless legs syndrome (RLS) is a sleep related movement disorder that occurs both in an idiopathic form and in symptomatic varieties. RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet. Therefore, a caseecontrol association study of these variants in ESRD patients was performed. Methods: The study genotyped 10 iRLS associated variants at four loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, and PTPRD, in two independent caseecontrol samples from Germany and Greece using multiplex PCR and MALDI-TOF (matrix assisted laser desorption/ionisation time-of-flight) mass spectrometry. Statistical analysis was performed as logistic regression with age and gender as covariates. For the combined analysis a CochraneManteleHaenszel test was applied. Results: The study included 200 RLS-positive and 443 RLS-negative ESRD patients in the German sample, and 141 and 393 patients, respectively, in the Greek sample. In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (Pnom≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (Pnom≤0.08, ORs 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (Pcorrected=0.0013, OR 1.47). Conclusions: This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab

<p>Abstract</p> <p>Background</p> <p>Although renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria.</p> <p>Case presentation</p> <p>A 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension. Laboratory findings included a white blood cell count of 49,800 cells/mm³with an absolute lymphocyte count of 47,000 cells/mm³, serum albumin of 2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection contained 7.1 g protein and significant haematuria. A peripheral blood smear showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes. Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing remission of the CLL and clinical resolution of the nephritic-range proteinuria.</p> <p>Conclusions</p> <p>A multidisciplinary approach to monitor both the malignancy and the glomerular lesions is crucial for the optimal management of paraneoplastic glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and rituximab successfully treated CLL-associated nephrotic syndrome in our patient, further studies are required to confirm efficacy in this setting.</p