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Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis
Get PDFAims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats
Epidemiological study on the incidence of haemorrhagic fever with renal syndrome in five Western Balkan countries for a 10-year period: 2006–2015
No full textBackground: Large-scale epidemics of haemorrhagic fever with renal syndrome (HFRS) have been reported mostly in Asia and Europe, with around 100,000 people affected each year. In the Southeast Europe, Balkan region, HFRS is endemic disease with approximately 100 cases per year. Our aim was to describe epidemiological characteristics of HFRS in five Western Balkan (WB) countries and to describe correlation between HFRS incidence and major meteorological event that hit the area in May 2014. Methods: National surveillance data of HFRS from Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia and Serbia obtained from 1 January 2006 to 31 December 2015 were collected and analysed. Results: In a 10-year period, a total of 1,065 HFRS patients were reported in five WB countries. Cumulative incidence rate ranged from 0.05 to 15.80 per 100.000 inhabitants (in North Macedonia and Montenegro respectively). Increasing number of HFRS cases was reported with a peak incidence in three specific years (2008, 2012, and 2014). Average incidence for the entire area was higher in males than females (5.63 and 1.90 per 100.000 inhabitants respectively). Summer was the season with the highest number of cases and an average incidence rate of 1.74/100.000 inhabitants across 10-year period. Haemorrhagic fever with renal syndrome incidence was significantly increased (7.91/100.000 inhabitants) in 2014, when a few months earlier, severe floods affected several WB countries. A strong significant negative correlation (r = −.84, p < .01) between the monthly incidence of HFRS and the number of months after May's floods was demonstrated for the total area of WB. Conclusion: Our findings demonstrate that the HFRS incidence had similar distribution (general, age, sex and seasonality) across majority of the included countries. Summer was the season with the highest recorded incidence. Common epidemic years were detected in all observed countries as well as a negative correlation between the monthly incidence of HFRS and the number of months after May's cyclone
Supplementary information for the article: Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z
Get PDFSupplementary material for: [https://doi.org/10.1007/s10571-022-01246-z]Related to the published version: [https://intor.torlakinstitut.com/handle/123456789/622
Supplementary material for: Mijin, N. D., Milošević, J., Filipović, N. R., Mitić, D., Anđelković, K., Polović, N. Đ., & Todorović, T. R. (2022). The effect of non-specific binding of Pd(II) complexes with N-heteroaromatic hydrazone ligands on the protein structure. Journal of the Serbian Chemical Society, 87(10), 1143. https://doi.org/10.2298/JSC220518050M
No full textPreviously, the cytotoxic actions of five Pd(II) complexes with bidentate N-heteroaromatic chelators (complexes 1–5) on a palette of several cancercell lines were investigated. However, the results of the cytotoxic activity didnot correlate with the hydrophobic character of the complexes. To gain furtherinsight into the structure–activity relationship, essential for the design of novelpotential drugs, other factors, such as non-specific interactions with cellularproteins, have to be taken into account. To explore the potential non-specificinfluence of the complexes on protein structures, ovalbumin (OVA) waschosen as a model system to mimic cellular non-specific crowding environments with high protein concentrations. A Fourier-transform infrared spectroscopy study implied that the binding of 3 and 4 led to only moderate alternations in the secondary structures of the protein, without the possibility to penetrate into hydrophobic core of the protein and disruption of protein native fold.Contrary, the effect of complex 5 on OVA secondary structures was concentration-dependent. While the lower concentration of complex 5 had no effecton OVA structure, a doubled concentration of complex 5 led to complete disruption of the content native-like secondary structures. The concentration-dependent effect of complex 5 on the changes in secondary structures and considerable increase in the exposure of OVA hydrophobic surfaces to water maybe related to a potential crosslinking that leads to OVA aggregation.Supplementary material for: [https://doi.org/10.2298/JSC220518050M]Related to published version: [https://intor.torlakinstitut.com/handle/123456789/1016
BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?
No full textBCG vaccination induces a memory-like response in innate immune cells known as
trained immunity. In this study, we investigated the modification of innate immune
cells by BCG vaccination in acute peritoneal inflammation. We induced peritonitis with
thioglycollate (TG) in young Albino Oxford male rats which were immunised s.c. with
a BCG vaccine (BCG group) or saline (control group) 7 days prior. Peritoneal cells were
examined for 7 days after TG injection by flow cytometry, and for NO production and
peroxidase activity. Prior in vivo BCG priming altered TG-elicited peritoneal lavage
cells as following: increased in vitro LPS and BCG stimulated NO production from total
cells compared to adherent cells (day 1); increased cell number (days 3 and 5);
increased percentage of inflammatory monocytes (SSCmidCD43lowCD11bmid) and
eosinophils (SSCHihiS48+CD43hi), and a higher level of surface CD11b expression on
CD163+ macrophages (day 5); increased in vitro LPS and BCG stimulated peroxidase
activity (days 5 and 7); and increased percentage of CD163+MHCII+ cells (day 7). On
day 7, cells from both experimental groups showed no production of NO in response to
in vitro stimulation. We conclude that BCG vaccination had a substantial effect on the
acute phase of sterile inflammation, which may lead to the later observed phenotypic
and functional changes that could be seen as accelerated resolution of inflammation
and possibly point to trained immune response
Comparative genomics of trimethoprim-sulfamethoxazole-resistant Achromobacter xylosoxidans clinical isolates from Serbia reveals shortened variant of class 1 integron integrase gene
No full textTrimethoprim-sulfamethoxazole (SXT) is the preferable treatment option of the infections caused by Achromobacter spp. Our study aimed to analyze the SXT resistance of 98 Achromobacter spp. isolates from pediatric patients, among which 33 isolates were SXT-resistant. The presence of intI1 was screened by PCR and genome sequence analyses. The intI1 gene was detected in 10 of SXT-resistant isolates that had shorter intI1 PCR fragments named intI1S. Structural changes in intI1S were confirmed by genome sequencing and analyses which revealed 86 amino acids deletion in IntI1S protein compared to canonical IntI1 protein. All IntI1S isolates were of non-CF origin. Pan-genome analysis of intI1S bearing A. xylosoxidans isolates comprised 9052 genes, with the core genome consisting of 5455 protein-coding genes. Results in this study indicate that IntI1S isolates were derived from clinical settings and that cystic fibrosis (CF) patients were potential reservoirs for healthcare-associated infections that occurred in non-CF patients
Predictors of Vancomycin-Resistant Enterococcus spp. Intestinal Carriage among High-Risk Patients in University Hospitals in Serbia
Get PDFThe predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3–7, 8–15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed
Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1
No full textS. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.Peer reviewed version: [https://intor.torlakinstitut.com/handle/123456789/651
Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation
No full textInflammation is a redistribution of immune cells, providing a more efficient elimination of the inflammatory offense. However, it is not limited to local microenvironment. In this study, the interaction of the effect of BCG priming and peritoneal inflammation on the remote inflammatory milieu of infected lung was investigated. Young male AO rats infected with Mycoplasma spp. were s.c. injected with BCG (3x105 CFU) or saline, and 7 days later received an i.p. injection of 7ml of thioglycollate (TG) or saline. Up to 7 days after TG injection, a broncho-alveolar lavage (BAL) was performed, and cells were analysed for their surface marker expression and NO production. Infected rats had a high percentage of HIS48HiCD11bHi neutrophils. BCG priming didn’t alter BAL cells phenotype, while TG injection increased the proportion of MHCII+CD11blow activated alveolar macrophages (aAMFs) on day 7. However, the BCG+TG group showed significant changes – percentage of HIS48HiCD11bHi neutrophils decreased from day 3, the share of aAMFs increased from day 5 and the share of MHCII+CD11b-AMFs increased on days 3-5. However, the percentage of B220+FSClow B lymphocytes were increased from day 1. Production of NO from BAL fluid cells was low in all groups. We conclude that BCG vaccination likely increased the number of circulating B lymphocytes, while TG-induced peritoneal inflammation potentially prevented their entry into the peritoneal cavity, forcing them into permissive tissues, such as lungs
Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans
Get PDFIncreased interest in microbiota calls for the thorough analysis of antibody reactivity to different microorganisms. As salivary IgA represents the first line of defence against microorganisms contacting mucosal surfaces, we explored the binding and specificity of salivary IgA by testing the binding of purified, FITC-labelled salivary IgA to different microorganisms in flow cytometry and conclude that this kind of analysis enables the differentiation of species/strains with high IgA binding capacity, which should be corroborated on a larger sample size. Further we compare, with in-house ELISA, the binding of polyclonal salivary IgA with the binding of polyclonal serum IgA from the same individuals to whole microbial cells and to purified microbial components. High correlations were obtained in total salivary IgA binding to Lactobacillus rhamnosus and Escherichia coli, very distant bacterial species, as well as to isolated bacterial components (r = .70–.97). The binding of total salivary IgA resembled the binding of both salivary IgA1 and IgA2, with IgA2 predominating. For serum polyclonal IgA repertoire, substantially higher specificity was obtained. Serum IgA binding to E. coli correlated best with serum IgA binding to lipopolysaccharide (r = .86), and serum IgA against L. rhamnosus correlated best with the anti-peptidoglycan IgA levels (r = .88). We have also detected that total serum IgA response is governed by either IgA1 or IgA2 response, depending on the nature of the antigen/s. We conclude that steady state salivary IgA repertoire, unlike serum IgA repertoire, consists of polyreactive antibodies with innate specificity, questioning its capacity to select resident microbiota