Elevated Level of DNA Damage and Impaired Repair of Oxidative DNA Damage in Patients with Recurrent Depressive Disorder

Background: Depressive disorder (DD), including recurrent DD (rDD), is a severe psychological disease, which affects a large percentage of the world population. Although pathogenesis of the disease is not known, a growing body of evidence shows that inflammation together with oxidative stress may contribute to development of DD. Since reactive oxygen species produced during stress may damage DNA, we wanted to evaluate the extent of DNA damage and efficiency of DNA repair in patients with depression. Material and Methods: We measured and compared the extent of endogenous DNA damage – single- and double-strand breaks, alkali-labile sites, and oxidative damage of the pyrimidines and purines – in peripheral blood mononuclear cells isolated from rDD patients (n=40) and healthy controls (n=46) using comet assay. We also measured DNA damage evoked by hydrogen peroxide and monitored changes in DNA damage during repair incubation. Results: We found an increased number DNA breaks, alkali-labile sites, and oxidative modification of DNA bases in the patients compared to the controls. Exposure to hydrogen peroxide evoked the same increased damage in both groups. Examination of the repair kinetics of both groups revealed that the lesions were more efficiently repaired in the controls than in the patients. Conclusions: For the first time we showed that patients with depression, compared with non-depresses individuals, had more DNA breaks, alkali-labile sites, and oxidative DNA damage, and that those lesions may be accumulated by impairments of the DNA repair systems. More studies must be conducted to elucidate the role of DNA damage and repair in depression

Steady state cooling conditions of fast neutron source for BNCT therapy.

Since 2001 the National Centre for Nuclear Research in Poland has been planning its BNCT test facility in Maria Research Reactor. The key issue is the beam quality needed to irradiate probes. For cellular cultures the thermal neutrons are optimal while for irradiating phantoms epithermal neutrons are required. Since the primary neutron energy spectrum from the reactor includes both fast neutrons and thermal ones, it is essential to shape the beam in a proper way. The beam will be based on two systems: neutron conversion system and the beam shaping system. The neutron conversion system is located on the periphery of the Maria reactor core and its main parts are uranium plates. Since the fission reaction occurs within plates the significant amount of heat is released that is why the proper cooling of the system has to be ensured. So far only one BNCT facility has applied neutron conversion system; it was in Massachusetts Institute of Technology [Carpenter, 2012]. However, the converter in MIT was placed outside the reactor, which is not the case here in ́Swierk, Poland. In this thesis the cooling requirements and the safety limits are defined for neutron conversion system, by means of Computational Fluid Dynamics analysis of steady state thermal hydraulic performance of installation. The results presented in this thesis were used to determine whether the existing pool cooling conditions are suitable to ensure safe operation of the neutron converter. The applied initial and boundary conditions in the test cases cover the entire spectrum of NC operating conditionsObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i Infraestructur

Preliminary computational and experimental design studies of the ISHTAR thermostatic rig for the high-temperature reactors materials irradiation

The Ir radiation System for High-Temperature Reactors (ISHTAR) thermostatic rig will be used to irradiate advanced core material samples in conditions corresponding to those prevailing in the high-temperature reactors (HTRs): these conditions include a stable temperature extending up to 1000°C in the helium atmosphere. Computational and experimental studies concerning the design have been conducted, proving the possibility of these conditions’ fulfi llment inside the rig while maintaining the safety limits for MARIA research reactor. The outcome is the thermostatic rig design that will be implemented in the MARIA reactor. Appropriate irradiation temperature will be achieved by a combination of electric heating with the control system, gamma heating, and a helium insulation gap with precisely designed thickness. The ISHTAR rig will be placed inside the vertical irradiation channel, which is located in the reactor pool. The device is being developed from scratch at the Nuclear Facilities Operation Department of the National Centre for Nuclear Research as a part of the GOSPOSTRATEG programm

Experimental study of ISHTAR thermostatic irradiation device for the MARIA research reactor

Materials and core components for the next generation power reactors technologies require testing that can be performed in existing research reactors. Such experiments employ devices dedicated to reflect the relevant thermal and neutron parameters simulating conditions present in, for example, but not limited to, HTGR reactors. A novel thermostatic irradiation device named ISHTAR (Irradiation System for High-Temperature Reactors) has been designed and constructed in the MARIA research reactor. Its mission is to enable irradiation of samples in controlled, homogeneous temperature field reaching 1000°C and inert gas atmosphere. The high temperature is achieved by a combination of electric and gamma heating, together with carefully designed thermal insulation. Additionally, samples holder made of graphite with high thermal conductivity enables the temperature homogenization in all directions. Device will be placed inside the Beryllium matrix of MARIA core and cooled with forced circulation of water from the reactor pool loop. This paper presents the outcome of experiments conducted with the rig prototype in external hydraulic mock-up of the MARIA reactor irradiation channel. The results have proved that the desired conditions for irradiation of the samples were achieved and their comparison against computational data has shown the adequacy of the design process. Finally, the loss of flow scenario was tested in protected and unprotected conditions (meaning with and without the safety system based on temperature feedback), proving the operational safety of the ISHTAR design. Experimental results will be used in the future to validate the numerical models (two and three dimensional) of the irradiation rig, providing an improved understanding of free convection and radiation phenomena modeling

Is the „silent” single nucleotide polymorphism (SNP) C1236T of ABCB1 gene associated with predisposition to depression development and efficiency of therapy? – preliminary study

Introduction: According to the World Health Organization about 350 million people around the world are affected by depression. Despite the high prevalence of this disease the mechanism of depression origination as well as the causes of the resistance to therapy are still not fully understood. ABCB1 gene encode P glycoprotein which is one of the components of blood-brain barrier. The main function of this protein is the efflux of many toxic compounds, including drugs, which may indicate potential association between the proper functioning of P glycoprotein and the susceptibility to the development of depressive disorders or the failure of antidepressant therapy. The objective of this study was to evaluate single nucleotide polymorphism (SNP) C1236T of the ABCB1 gene in the group of patients with recurrent depressive disorder (rDD) and to estimate the possible association of this polymorphism with the response to antidepressant therapy. Material and methods: C1236T was evaluated in 30 patients with rDD. Genotyping was performed using automated sequencing (the Sanger method). The results were compared with those obtained from the control group which consisted of 96 blood donors from the local blood bank. Results: No statistically significant difference in the frequency of genotypes (p=0.0665) and allele (p=0.1489) for the SNP C1236T of ABCB1 gene was found between the patients with rDD and the control group. No correlation between C1236 and the age when the disease was stated (p=0.0807). Neither the association between genotypes and the severity of depressive symptoms before treatment (p=0.7956) nor the association with effectiveness of the therapy (p=0.2051) were found. Conclusions: On the basis of the results of the preliminary study, C1236T of ABCB1 gene have no influence on the predisposition to rDD, the severity of depressive symptoms and the efficiency of antidepressant therapy have not been stated, either.Streszczenie Wstęp: Według danych Światowej Organizacji Zdrowia depresja dotyka około 350 milionów osób na całym świecie. Jednak pomimo powszechnego występowania, zarówno etiologia tej choroby, jak i przyczyny oporności na leczenie w dalszym ciągu nie są w pełni poznane. Gen ABCB1 koduje glikoproteinę P, która jest jednym z elementów bariery krew-mózg. Główną funkcją białka jest usuwanie związków toksycznych, w tym także leków, co może wskazywać na potencjalny związek między prawidłowym działaniem glikoproteiny P a predyspozycją do rozwoju zaburzeń depresyjnych czy niepowodzeniem terapii lekami przeciwdepresyjnymi. Celem pracy była ocena polimorfizmu pojedynczego nukleotydu (ang. single nucleotide polymorphism - SNP) C1236T genu ABCB1 wśród chorych na zaburzenia depresyjne nawracające (ang. recurrent depressive disorder - rDD) oraz oszacowanie potencjalnego związku tego polimorfizmu z odpowiedzią na terapię lekami przeciwdepresyjnymi. Materiał i metody: Polimorfizm C1236T oceniono w grupie 30 pacjentów, u których zdiagnozowano rDD. Genotyp określono wykorzystując technikę automatycznego sekwencjonowania metodą Sangera. Otrzymane wyniki porównano z wynikami grupy kontrolnej, którą stanowiło 96 dawców krwi z lokalnego banku krwiodawstwa. Wyniki: Nie stwierdzono istotnych statystycznie różnic w częstości występowania poszczególnych genotypów (p=0,0665) i alleli (p=0,1489) polimorfizmu C1236T genu ABCB1 między grupą pacjentów z rDD a grupą kontrolną. Nie wykazano również zależności pomiędzy C1236T a wiekiem w chwili diagnozy rDD (p=0,0807), nasileniem objawów depresji przed rozpoczęciem terapii (p=0,7956) czy skutecznością leczenia przeciwdepresyjnego (p=0,2051). Wnioski: Na podstawie wyników badania wstępnego, stwierdzono brak wpływu polimorfizmu C1236T genu ABCB1 na predyspozycję do rozwoju rDD, nasilenie objawów depresji w chwili diagnozy czy skuteczność terapii przeciwdepresyjnej

Self-injury among prisoners — relationship to psychosocial factors

Background. Penitentiary institutions are particularly liable to the emergence and spreading of detrimental social phenomena. Compulsory stay in a closed institution and the necessity to adjust to conditions dramatically different from those of the prisoner’s former life are often a source of frustration. Self-aggression in prisons usually takes the form of self-injury. Self-mutilation is often a ticket to being promoted in the prison subculture pecking order, or a way to enforce some earlier unattainable demands. Frequently it may be also the prisoner’s response to deprivation of his basic needs. Material and methods. The anonymous study was conducted on the premises of Prison No. 2 in Lodz, between December 2006 and March 2007. Participants were 50 male prisoners aged 22-60; in that number 25 men had committed various self-injuries, and 25 had never attempted self-mutilation. Personal data were collected using a questionnaire developed by the authors for the purposes of this study. Results. Self-injuries were committed most frequently by prisoners aged below 30, with primary or vocational education, from broken homes. Their term of imprisonment was over 5 years, they were recidivists incarcerated more than once, and in the majority of cases (92%) belonged to prison subculture. As many as 68% of the prisoners under study committed self-injury repeatedly, most often due to emotional motives. Conclusions. Psychosocial variables were found to correlate with the frequency and type of self-injury among prisoners. The more detrimental psychosocial variables, the more frequent were self-injuries.Wstęp. Instytucja penitencjarna to miejsce szczególnie podatne na powstawanie i utrzymywanie się niekorzystnych zjawisk społecznych. Przymusowy pobyt w zakładzie zamkniętym oraz konieczność zaaranżowania sobie życia w warunkach diametralnie odmiennych niż dotychczas często wywołują frustrację. Autoagresja w więzieniach przejawia się zazwyczaj w postaci samouszkodzeń. Samookaleczenie często bywa przepustką do awansu w hierarchii więziennej subkultury bądź też pozwala na wyegzekwowanie wcześniej nieosiągalnych żądań. Niejednokrotnie jest także reakcją na deprywację podstawowych potrzeb. Materiał i metody. Badania przeprowadzano anonimowo na terenie Zakładu Karnego nr 2 w Łodzi w okresie od grudnia 2006 roku do marca 2007 roku. Łącznie przebadano 50 mężczyzn w wieku 22-60 lat, w tym 25 dokonywało różnych samouszkodzeń, a 25 nigdy nie podejmowało prób samookaleczeń. W celu zgromadzenia danych personalnych dotyczących respondentów posłużono się ankietą opracowaną na potrzeby badania. Wyniki. Samouszkodzeń najczęściej dokonywali więźniowie w wieku do 30. roku życia, z wykształceniem podstawowym lub zawodowym, pochodzący z niepełnych rodzin, odbywający karę pozbawienia wolności dłuższą niż 5 lat i przebywający w więzieniu po raz kolejny. W większości przypadków (92%) byli to więźniowie przynależący do subkultury więziennej. Aż 68% spośród badanych osób dokonywało samouszkodzeń wielokrotnie, najczęściej z pobudek emocjonalnych. Wnioski. Stwierdza się korelację pomiędzy czynnikami psychospołecznymi a częstością i charakterem dokonywanych samouszkodzeń wśród osób przebywających w izolacji więziennej. Im bardziej niekorzystnie oddziałują czynniki psychospołeczne, tym więcej odnotowuje się samouszkodzeń

Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population

Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene—genotype C/A and C/A-A/A

MARIA Reactor Irradiation Technology Capabilities towards Advanced Applications

The MARIA research reactor is designed and operated as a multipurpose nuclear installation, combining material testing, neutron beam experiments, and medical and industrial radionuclide production, including molybdenum-99 (99Mo). Recently, after fuel conversion to LEU and rejuvenation of the staff while maintaining their experience, MARIA has been used to respond to the increased interest of the scientific community in advanced nuclear power studies, both fission and fusion. In this work, we would like to introduce MARIA’ s capabilities in the irradiation technology field and how it can serve future nuclear research worldwide