Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling.

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Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

Kidney damage induced by sub-chronic fine particulate matter exposure.

Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole-cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2- and caveolin-1-mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan-deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.

Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in Patients

Metabolomics in the Developing Human Being

Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n = 9) and negative (n = 7) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra- and interfamilial phenotype variability of MUC1 related kidney disease.

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Single molecule real time sequencing in ADTKD- MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations

MUC1 is a transmembrane glycoprotein, apically expressed in most epithelial cells, used in the differential diagnosis of carcinomas and for discrimination of tumors of non-epithelial origin showing epithelioid features. Little attention has been paid so far though, on its possible significance in embryonic tissues. A preliminary study from our group revealed MUC1 expression in the cap mesenchymal cells during human nephrogenesis, suggesting a role for MUC1 in the process of mesenchymal-to-epithelial transition. This study aimed at investigating the expression pattern of MUC1 in various developing structures of human fetal kidney. Expression of MUC1 was examined in kidneys of 5 human fetuses. MUC1 immunoreactivity was detected in ureteric bud tips, in collecting tubules, in cap mesenchymal cells undergoing the initial phases of mesenchymal-to-epithelial transition, in renal vesicles, comma-bodies, and S-shaped bodies. Our previous preliminary report suggested a role for MUC1 in the initial phases of the process of mesenchymal-to-epithelial transition. The present data suggest that MUC1 expression characterizes multiple structures during human nephrogenesis, from the ureteric bud, to the initial phases of mesenchymal-to-epithelial transition and that MUC1 should be added to the genes activated during the process of mesenchymal-to-epithelial transition in the cap mesenchyme of human kidney.

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MUC1 marks collecting tubules, renal vesicles, comma- and S-shaped bodies in human developing kidney

AIM: To analyze the effects on the kidney of hypoxia-reoxygenation in an experimental model of normocapnic asphyxia.

METHODS: To this end, 40 newborn Landrace/Large-White piglets aged 1-4 d were studied in this work. Hypoxia was induced by decreasing the inspired fiO2 to 0.06-0.08. Animals were resuscitated with different fiO2 and subdivided into 4 groups: group 1, 2, 3 and 4 received 18%, 21%, 40% and 100% O2 respectively. Macroscopic examination was carried out to evidence possible pathological features. Tissue sample were obtained from both kidneys. Four or five micron paraffin sections were stained with H-E and PAS stain and examined under an optical microscope.

RESULTS: Pathological changes, mainly affecting tubular cells, were observed in the vast majority of kidneys of asphyxiated piglets. The most frequent tubular changes were: tubular casts (95%), tubular dilatation (87.5%), tubular vacuolization (70%), tubular eosinophilia (52.5%), sloughing (50%), fragmentation of the brush border (50%), oedema (32.5%), apoptosis (15%) and glomerular changes (meningeal cell proliferation, capsular adhesion between the flocculus and Bowman’s capsule, glomerulosclerosis and fibrous or cellular crescents associated with collapse of the glomerular tuft). Statistical analysis was carried out on changes observed when the animals were allocated in the 4 groups (χ2-test 0.05). The statistical analysis showed no evidence of differences regarding kidney lesions among the animals groups.

CONCLUSION: Our data show that renal pathology in newborn piglets is characterized by interindividual variability to hypoxia and is not associated with oxygen concentration.

Histopathology of renal asphyxia in newborn piglets: Individual susceptibility to tubular changes.

Metabolomics in perinatal renal asphyxia

Introduction: To investigate the level of knowledge of Greek dentists in cardiopulmonary resuscitation (CPR) and of the use of the Automated External Defibrillator (AED) before and after participating in a European Resuscitation Council (ERC) CPR/AED course. Materials and methods: A theoretical knowledge questionnaire consisting of multiple choice questions was completed by the participants at the beginning of the CPR/AED course. The participants were re-evaluated at the end of the course, while the evaluation procedure consisted of two distinct parts: a 10-min written test which preceded a simulated cardiac arrest scenario. Vasileios Schizogiannis DDS1, Athanasios Chalkias PhD1,2, Euaggelia Kouskouni PhD1, Nicoletta Iacovidou PhD2,3, Theodoros Xanthos PhD2,4 Results: The average performance of the participants in pre-course written test was satisfactory, while the dentists who had attended a CPR/AED course in the past achieved significantly higher initial performance in contrast to their colleagues (p=0.028). There was a statistically significant increase in post-course test score compared to pre-course test score (8.3±1.2 vs. 5.7±1.9, respectively; p<0.001). In addition, participation in a CPR/AED course had a positive effect on the participant’s skills, as their performance was excellent at the end of the course. Conclusions: Dentists’ resuscitation knowledge and skills were significantly improved after participating in ERC CPR/AED courses. ISSN 2466-2623 USTANOVA 1 National and Kapodistrian University of Athens, Medical School, Postgraduate Study Program (MSc) “Cardiopulmonary Resuscitation”, Athens, Greece 2 Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece 3 2nd Department of Obstetrics and Gynecology, Neonatal Division, National and Kapodistrian University of Athens, Medical School, Athens, Greece 4 European University Cyprus, School of Medicine, Nicosia, Cyprus AUTOR ZA KORESPODENCIJU: Dr. Athanasios Chalkias, National and Kapodistrian University of Athens, Medical School, Postgraduate Study Program (MSc) “Cardiopulmonary Resuscitation”, 3 Ir. Politechniou Av., 18532, Piraeus, Greece. Tel.: +302110121756; Fax: +302110121758, Email: thanoschalkias@yahoo.gr KLJUČNE REČI: cardiopulmonary resuscitation; automated external defibrillator; dentists DATUM PRIJEMA RADA 10. oktobar 2015. DATUM PRIHVATANJA RADA 20. oktobar 2015. DATUM OBJAVLJIVANJA 10. jun 2016. Introduction Cardiac arrest is a major cause of death worldwide (1-3). In the United States (USA), the referring frequency of occurrence of out-of-hospital cardiac arrest (OHCA) in individuals aged between 50 and 79 is 1.9/1000 per year (2). In Europe, the annual incidence of out-of-hospital cardiac arrest (OHCA) for all rhythms is 38 per 100,000 population, while the annual incidence of ventricular fibrillation (VF) arrest is 17 per 100,000 (3). On initial heart rhythm analysis, about 25–30% of OHCA victims have VF, but when the rhythm is recorded, soon after collapse, the incidence can be as high as 59–65% (4,5). For every minute that defibrillation is delayed, survival from witnessed VF decreases by 10–12%, while survival to hospital discharge can be as high as 75%, if defibrillation is performed within 3 min of collapse (6-8). In a British study, cardiac arrest was extremely rare in dental practice with an incidence of 0.002 cases per dentist per year (9), while in Germany, it was estimated that one sudden cardiac arrest occurs per 638,960 patients in dental practice (10). Considering however that dentists today treat a growing number

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Evaluation of resuscitation knowledge and skills in dentists before and after a European Resuscitation Council CPR/AED course

A case of horseshoe kidney is reported in a 11 week-old fetus affected by trisomy 18. Macroscopic examination did not show any other pathological change. The histological picture of the fused-kidney was characterized by architectural and glomerular changes. At x 100 magnification, large areas of metanephric mesenchyme, characterized by spindle cells surrounded by a loose oedematous stroma, were detected in the deep cortex and in the medulla. At higher power, multiple glomerular changes were observed. Maldeveloped glomeruli showed enlarged capsular spaces, adhesions between vascular tuft and capsular cells, podocytes in multiple layers, and large glomerular bodies formed by two vascular tufts. Our data confirm previous reports on glomerular changes in horseshoe kidney, and reinforce the hypothesis that horseshoe kidney should not be considered a simple fusion problem, but a complex developmental abnormality, possibly involving glomerular development.

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Nicoletta Iacovidou

Papers

MUC1 marks collecting tubules, renal vesicles, comma- and S-shaped bodies in human developing kidney

Histopathology of renal asphyxia in newborn piglets: Individual susceptibility to tubular changes.

Metabolomics in perinatal renal asphyxia

Evaluation of resuscitation knowledge and skills in dentists before and after a European Resuscitation Council CPR/AED course

Glomerular changes in trisomy 18-related horseshoe kidney: report of a case and review of the literature