Maprotiline treatment differentially influences cardiac β-adrenoreceptors expression under normal and stress conditions

Alterations in cardiac function were observed in antidepressants treated patients and published in several clinical reports. These detected changes could be either a consequence of the treatment or of depression itself, which has already been proved to be a risk factor in heart diseases. In order to determine a possible influence of chronic treatment with norepinephrinergic reuptake inhibitor, maprotiline, on the heart, we investigated gene expression of cardiac β-adrenoceptors both in controls and in animals with signs of depression. The rats were divided into two groups, unstressed controls and those exposed to chronic unpredictable mild stress (CUMS). The groups were further divided into two subgroups, one receiving daily intraperitoneal injections of vehicle (sterile water) and another one maprotiline (10 mg/kg) for four weeks. Tissue samples were collected after the last application. Gene expression of cardiac β1- and β2-adrenoceptor was determined using Real-time RT-PCR analysis. Our results show that in control animals expression of both adrenoreceptors was decreased in the right atria after 4 weeks of maprotiline application. Contrary, the same treatment led to a significant increase in expression of cardiac β1-adrenoceptor in the stressed rats, with no change in the characteristics of β2-adrenoceptor. Our findings might reflect the that molecular mechanisms are underlying factors involved in the development of cardiovascular diseases linked with antidepressant treatment.Vários relatórios clínicos observaram alterações de funcionamento cardíaco de pacientes depressivos que foram tratados com os antidepressivos. As alterações detectadas podem ser consequência do tratamento ou, por outro lado, da depressão que, como se tem provado, é um fator de risco no caso de doenças cardíacas. De modo a determinar a possível influência de tratamento crônico com o inibidor da recaptação de norepinefrina, maprotilina, no coração, foi investigada a expressão do gene aos receptores β-adrenérgicos cardíacos dos animais em grupos de controle e em grupos com sinais de depressão. Os ratos foram divididos em grupos de controle não estressados e os grupos de ratos submetidos ao estresse crônico moderado imprevisível (CUMS). Os grupos foram, ainda, divididos em dois subgrupos, que, durante quatro semanas, diariamente receberam injeções intraperitoneais de placebo (água estéril) ou de maprotilina (10 mg/kg). As amostras de tecido foram coletadas após a última aplicação. A expressão do gene aos receptores adrenérgicos β1 e β2 foi determinada utilizando a análise PCR quantitativa em tempo real (RT-PCR). Os nossos resultados demonstram a diminuição de expressão dos ambos os receptores adrenérgicos no átrio direito dos animais do grupo de controle depois de quatro semanas de aplicação de maprotilina. Em contraste, o mesmo tratamento conduziu ao aumento significativo na expressão do receptor β1-adrenérgico no coração dos ratos estressados, sem qualquer alteração nas características do receptor β2-adrenérgico. Estes resultados podem refletir os mecanismos moleculares envolvidos no desenvolvimento de doenças cardiovasculares associadas ao tratamento com os antidepressivos

Increased il-33 and il-17 in colorectal carcinoma patients with severe disease

© 2020, University of Kragujevac, Faculty of Science. All rights reserved. Colorectal cancer (CRC) represents one of the most common cancers. It is frequently diagnosed at advanced stages, indicating on need for new diagnostic markers. The aim of this study was to determine systemic and fecal values of IL-17 and IL-33 in patients with CRC and the relationship with clinicopathological aspects of disease. The blood samples and feces liquid fraction of 50 patients with CRC were analyzed. Serum and fecal levels of IL-33 and IL-17 were measured using sensitive enzyme-linked immu-nosorbent assay (ELISA) kits. Fecal levels of Il-33 and IL-17 were increased in CRC patients with poor tumor tissue differentiation. Serum IL-33 and fecal IL-17 were increased in patients with presence of lung/liver metastasis or peritoneal carcinomatosis, respec-tively, while enhanced fecal IL-33 was detected only in patients with peritoneal carcinomatosis. Positive correlation between IL-33 and IL-17 values in sera and feces, respectively was also observed. We believe that increased local values of IL-33 and IL-17, reflected trough higher fecal concentration, in CRC patients with poor tumor tissue differentiation and with presence of lung/liver metastasis or peritoneal carcinomatosis may be considered as a sign of the tumor’s malignant progression and, consequently, of a poor prognosis for patients

INDIVIDUALIZATION CONCEPT IN HOUSING ARCHITECTURE

Although single-family housing in the city is considered higher quality and preferred type of housing, housing crisis, as a permanent actual problem in the world, requires adequate solutions. In this sense, housing in multi-family housing buildings can be considered as a necessity (social, moral, economic, etc.), but in fact, now and in the future, it is the main form of housing construction which can give the solution for housing problems. However, to make this housing type more attractive and acceptable to the occupants, it is necessary to improve it by the implementation of individualization modalities, and in that way make its qualities much closer to the preferred single-family housing

PARAMETERS FOR IMPROVEMENT OF THE HOUSING QUALITY IN SOCIAL HOUSING DWELLINGS

Abstract. Experiences of the countries with developed social housing sector indicate that the role of social housing should not be treated in a limited manner, considered to be just a roof over one’s head, whereby housing quality will be neglected. Contemporary approaches to the development of social housing models are focused on users themselves, with a special concern for the housing quality. Because the units of social housing have the minimal size, it is necessary to provide such amenities so as to overcome the shortage of usable housing space. It is also desirable that the design of social housing dwellings should have a simulative effect on the tenants within this areas. This paper discusses the spatial and physical parameters which could affect the housing quality of this type of dwellings. Key words: housing quality, housing standard, housing unit, social housing

Risk factors associated with poor clinical outcome in pyogenic spinal infections : 5-years’ intensive care experience

Introduction: Management of pyogenic spinal infections (PSI) after the development of neurological deficit has not been specifically addressed in the literature. We aimed to describe real-life clinical outcomes of PSI in patients admitted to an intensive care unit with neurological deficit and identify factors associated with good prognosis. Methodology: Consecutive patients admitted to ICU with a possible diagnosis of spinal infection over five years’ period were included. Descriptive statistics were performed to examine the demographics and clinical parameters. Results: The majority (71%) of patients were male. The mean age was 57.4 years (27-79), and 71% were > 50 years old. At least one underlying risk factor was identified in 68% of the patients; the most common comorbidity was diabetes mellitus (DM). All patients have presented with fever accompanied by a neurological deficit (86%) and back pain (79%). A complete recovery was achieved in 25% of patients. However, the majority of patients had adverse outcomes with 21.4% mortality, and 43% remaining neurological sequelae. Increased age with a cut-off of 65 years and pre-existing DM were identified as being associated with poor outcome. Conclusion: Mortality among patients admitted to ICU with PSI was significantly higher than reported in the literature. The residual neurological deficit was common, one-third of patients had remaining neurological sequelae, and only one-fourth had complete recovery. Increased age and background DM were the most important determinants of poor clinical outcome. The impact of DM appears to be much more important than currently recognised in this population.Publisher PDFPeer reviewe

SERUM LEVELS OF INTERLEUKIN-6 AND TUMOR NECROSIS FACTOR-ALPHA IN EXACERBATION AND REMISSION PHASE OF SCHIZOPHRENIA

Background: The variations in proinflamatory cytokine levels have been associated with schizophrenia (SCH), duration of illness, psychopathology and treatment. The aim of the study was to investigate serum levels of interleukin-6 (IL-6) and tumor necrosis factoralpha (TNF-α) in schizophrenic patients during exacerbation and remission, and its association with course of illness and therapy. Subjects and methods: We measured serum levels of IL-6 and TNF-α in 43 schizophrenic patients in exacerbation and remission and compared them to 29 healthy controls, matched by sex, age, body mass index (BMI) and smoking habits. The severity of psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results: There was no difference in levels of IL-6 and TNF-α in exacerbation compared to remission in schizophrenic patients. IL-6 was higher and TNF-α was lower in schizophrenic patients in both exacerbation and remission in comparison with healthy controls. TNF-α in exacerbation was in negative correlation with IL-6 in remission. No statistical significance was found between levels of cytokines and sex, age, BMI, smoking habits, antipsychotic medication, duration of treatment and duration of illness. IL-6 levels were in positive correlation with the age of onset and the duration of untreated psychosis. In schizophrenic patients on adjunctive treatment with mood stabilizers, TNF-α levels increased in remission. Conclusion: Our results suggest that the connection between schizophrenia, cytokines and medication is multifaceted, and not necessarily linear. Adjunct mood stabilizers not only ameliorate psychopathology, but might convey immunomodulatory effects as well. Further longitudinal studies could elucidate potential beneficial effect of combined therapy in treatment of SCH

Expression pattern of circulating long non-coding RNA GAS5 as a novel biomarker in non-small cell lung cancer patients

Introduction: The finding that long noncoding RNAs (lncRNAs) originating from tumor cells could be found in general circulation has prompted the idea to use lncRNAs as noninvasive diagnostic biomarkers of particular diseases. In this study we explored the expression pattern of circulating GAS5..

WP4 ‐ Modernization of teaching contents 4.1. Need analysis for knowledge refreshment

This brochure is a result of the TEMPUS project “Building Capacity of Serbian Agricultural Education to Link with Society” (CaSA) 544072-TEMPUS-1-2013-1-RS-TEMPUS-SMHES (2013-4604/001-001). Daniela Šćepanović and Steve Quarrie were responsible for questionnaire construction, assisted by Slavica Čolić. Analysis of questionnaires was coordinated by Daniela Šćepanović, as well as final preparation and presentation of the results. For final document preparation, all CaSA Steering Committee members gave valuable contribution. For brochure final preparation Daniela Šćepanović, Vesna Poleksić and Goran Topisirović were in charge.TEMPUS Project: Building Capacity of Serbian Agricultural Education to Link with Society (CaSA) 544072-TEMPUS-1-2013-1-RS-TEMPUS-SMHES (2013 – 4604 / 001 - 001) Coordinator: University of Belgrade, Faculty of Agricultur

TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation

Background Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA—the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP–TET interplay. Results Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. Conclusions According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine