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Role of inactivated influenza vaccine in regulation of autoimmune processes in experimental autoimmune encephalomyelitis
No full textExperimental autoimmune encephalomyelitis (EAE) is characterized by appearance of anti-myelin autoantibodies in the blood and with the increased expression of MHC (major histocompatibility complex) class I and II antigens in the brain tissue. Although there is an evidence of possible linkage between influenza vaccination and development of autoimmune processes, the precise mechanisms of action of this vaccine on EAE-induction is still unclear. In this study, effects of influenza vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test and expression of MHC class I and II molecules immunohistochemistry were examined in the brain of C57BL mice with EAE. EAE was induced by MOG(35-55) protein in 16 of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE mice and to eight previously nontreated mice. A significant increase of anti-influenza antibody was detected in vaccinated mice compared to nontreated mice. Also, significant increase of antimyelin antibodies was detected in mice with EAE compared to vaccinated group without EAE and control group, respectively. In EAE-influenza vaccinated mice, a mild but not significant increase of antimyelin antibodies was detected, compared to EAE mice. High expression of MHC-II and mild expression of MHC-I were detected in the brain of mice with EAE. No expressions were detected in vaccinated and normal intact brains. Similar staining was found between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes
Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency
No full textThis study explores the role of ovarian hormones in the phenotypic shaping of peripheral T-cell pool over the reproductive lifespan of rats. For this purpose, 2-month-old prepubertally ovariectomised (Ox) rats, showing oestrogen and progesterone deficiency, and 11-month-old Ox rats, exhibiting only progesterone deficiency, were examined for thymus output, and cellularity and composition of major TCR alpha beta+ peripheral blood lymphocyte (PBL) and splenocyte subsets. Although ovariectomy increased thymic output in both 2- and 11-month-old rats, the count of both CD4+ and CD8+ PBLs and splenocytes increased only in the former. In the blood and spleen of 11-month-old Ox rats only the count of CD8+ cells increased. Although ovariectomy affected the total CD4+ count in none of the examined compartments from the 11-month-old rats, it increased CD4+FoxP3+ PBL and splenocyte relative proportions over those in the age-matched controls. The age-related differences in the cellularity and the major subset composition in Ox rats were linked to the differences in the ovarian steroid hormone levels registered in 2- and 11-month-old rats. The administration of progesterone to Ox rats during the seven days before the sacrificing confirmed contribution of this hormone deficiency to the ovariectomy-induced changes in the TCR alpha beta+ PBL and splenocyte pool from 11-month-old rats. The expansion of the CD8+ splenocyte subset in the 11-month-old Ox rats reflected increases in cellularity of memory and, particularly, nave cells. This was due to greater thymic output of CD8+ cells and homeostatic proliferation than apoptosis in 11-month-old Ox rats when compared with age-matched sham-Ox control rats. The homeostatic changes within CD8+ splenocyte pool from 11-month-old Ox rats, most likely, reflected the enhanced splenic IL-7 and TGF-beta mRNA expression. Overall, in adult female rats, circulating oestrogen and progesterone provide maintenance of T-cell counts, a diversity of T-cell repertoire, and the main T-cell subset composition in the periphery. Progesterone deficiency affects mainly the CD8+ lymphocyte compartment through increasing thymic CD8+ cell export and upsetting homeostatic regulation within the CD8+ splenocyte pool. These alterations were reversible through progesterone supplementation. (C) 2013 Elsevier GmbH, All rights reserved
Aggregation Factor as an Inhibitor of Bacterial Binding to Gut Mucosa
No full textModern research in the area of probiotics is largely devoted to discovering factors that promote the adherence of probiotic candidates to host mucosal surfaces. The aim of the present study was to test the role of aggregation factor (AggL) and mucin-binding protein (MbpL) from Lactococcus sp. in adhesion to gastrointestinal mucosa. In vitro, ex vivo, and in vivo experiments in rats were used to assess the adhesive potential of these two proteins expressed in heterologous host Lactobacillus salivarius BGHO1. Although there was no influence of MbpL protein expression on BGHO1 adhesion to gut mucosa, expression of AggL had a negative effect on BGHO1 binding to ileal and colonic rat mucosa, as well as to human HT29-MTX cells and porcine gastric mucin in vitro. Because AggL did not decrease the adhesion of bacteria to intestinal fragments in ex vivo tests, where peristaltic simulation conditions were missing, we propose that intestinal motility could be a crucial force for eliminating aggregation-factor-bearing bacteria. Bacterial strains expressing aggregation factor could facilitate the removal of pathogens through the coaggregation mechanism, thus balancing gut microbial ecosystems in people affected by intestinal bacteria overgrowth
Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice
No full textA small dose of the Bordetella pertussis vaccine is used as an adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE) in mice. The effects of two doses of the Pertussis vaccine on clinical signs, antibody titers, and the expression of CD4 and MHC molecules in brain tissue sections of mice with EAE were examined. EAE was induced by spinal cord homogenate in Complete Freund adjuvant (CFA) in 30 of 40 C57BL/6 mice divided in groups: EAE mice with a small adjuvant dose of the Pertussis vaccine (EAE-1), EAE mice with a human dose of the Pertussis vaccine (EAE-2), EAE mice (EAE-3). None of the mice from the EAE groups progressed to severe EAE. Five mice from the EAE-2 group were found dead on the 13th day post-immunization. A significant increase of anti-MOG (myelin oligodendrocyte glycoprotein) antibodies was detected in mice with EAE compared to non-treated mice. Myelin loss and brain tissue lesions were observed in EAE-1 and EAE-2 mice compared to EAE-3 and non-treated mice. A high expression of MHC-II and a mild expression of MHC-I was detected in the brains of mice with EAE. No expressions were detected in intact brains. Scattered CD4-positive cells were detected in the brains of EAE-1 and EAE-2 mice compared to EAE-3 and non-treated mice. A small dose of the Bordetella pertussis vaccine could maintain the developed clinical signs and histological changes in mice with EAE, while higher doses led to additional adverse effects. The expression of CD4 and MHC class I and II molecules, as well as an increase in anti-MOG antibodies could be used as markers capable of monitoring the development and progression of EAE
Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment
No full textThe present study, through quantification of tyrosine hydroxylase (TH) expression and catecholamine (CA) content in the presence and in the absence of alpha-methyl-p-tyrosine (AMPT), a TH inhibitor, in adult thymic organ (ATOC) and thymocyte culture, demonstrated that thymic cells produce CAs. In addition, in ATOC an increase in beta(2)-adrenoceptor (AR) mRNA expression and beta(2)-AR thymocyte surface density was registered. Furthermore, AMPT (10(-4) M), as propranolol (10(-4) M), augmented thymocyte apoptosis and diminished thymocyte proliferation in ATOC. Propranolol exerted these effects acting on CD3(high) thymocytes. However, in thymocyte cultures, propranolol (10(-6) M) acting on the same-thymocyte subset exerted the opposing effect on thymocyte apoptosis and ConA-stimulated proliferation. This suggested that, depending on thymocyte microenvironment, differential effects can be induced through the same type of AR. Additionally, arterenol (10(-8) to 10(-6) M), similar to propranolol, diminished apoptosis, but increased ConA-stimulated thymocyte proliferation in thymocyte culture. However, differently from propranolol, arterenol affected manly CD3- thymocyte subset, which harbors majority of alpha(1)-AR+ thymocytes. Additionally, arterenol showed a dose-dependent decrease in efficiency of thymocyte apoptosis and proliferation modulation with the rise in its concentration. Considering greater affinity of arterenol for alpha(1)-ARs than for beta(2)-ARs, the previous findings could be attributable to increased engagement of beta(2)-ARs with the rise of arterenol concentration. Consistently, in the presence of propranolol (10(-6) M), a beta-AR blacker, the arterenol (10(-8) M) effects on thymocytes were augmented. In conclusion, thymic endogenous CAs, acting through distinct AR types and, possible, the same AR type (but in different cell microenvironment) may exert the opposing effects on thymocyte apoptosis/proliferation. (C) 2014 Elsevier B.V. All rights reserved
Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study
No full textThe CmbT substrate specificity and its role as a proton motive force-driven drug efflux pump at a molecular level were investigated in the study. In that order, 3D-quantitative structure-activity relationship (3D-QSAR) study was applied for selection of molecular determinants of multidrug recognition by CmbT. CmbT multidrug resistance protein of Lactococcus lactis contributes to extruding the structurally, chemically, and pharmacologically diverse range of substrates out of bacterial cells. This function of CmbT may result in the failure of antibiotic therapy. Homology model of CmbT protein was constructed and further opthnized. The 3D-QSAR model predictive potential was proved by use of leave-one-out cross validation Of the training set (Q(2): 0.69, R-observd(2) (vs).(Predicted) : 0.918, RMSEE: 0.193) and verification set (R-Observed vs predicted(2) : 0.704, RMSEP: 0.289). The results obtained in this study showed that high CmbT affinities to ethidium, sulbactam, and sulfathiazole could be related to the absence of significant unfavourable interactions. In contrast, the presence of specific unfavourable interaction between two hydrogen bond donor groups in bacitracin, apramycin, novobiocin, vancomycin, kanamycin, gentamycin, and tobramycin is found to be the main reason for their lower CmbT affinities. In addition, membrane position of the CmbT binding site and positive correlation between substrates lipophilicity (log D-PH so) and CmbT affinity strongly indicates that CmbT recognizes its substrates within the membrane
Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1 beta expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro
Get PDFIn humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6-(adult), 24-(old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1 beta and IL-6) and antiinflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-alpha and IL-6 mRNAs, but greater amount of IL-1 beta mRNA. On the other hand, cells fromlong-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-alpha and IL-6 mRNA expression, and comparable expression of IL-1 beta mRNA relative to adult rats. Consequently, IL-10/IL-1 beta mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained = 95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-alpha and IL-6 concentrations were lower; IL-1 beta concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from longlived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity
Intra- and inter-population variability of food preferences of two natrix species on the Balkan peninsula
No full textIn aquatic and surrounding terrestrial ecosystems, snakes of the genus Natrix are among the top predators, feeding predominantly on fishes and amphibians, but also on other reptiles and small mammals. In the diets of Natrix natrix and N. tessellata, preferred food items vary geographically and during ontogeny. To understand these variations, we collected data on their diet composition in several habitats (river, wetlands, and two types of lakes), some of which are under severe anthropogenic pressures. Both Natrix species were able to quickly adapt to changes in available prey, and to feed even on non-indigenous, invasive, and potentially hazardous fish. Disturbed ecosystems are particularly susceptible to invasions. Therefore, if alien fishes become dominant, they may threaten populations of native snakes. On the other hand, semi-aquatic snakes can contribute to natural regulation of alien fish species abundance. The preliminary results presented herein emphasize the urgent need for integrative studies of natricine snakes and their prey ecology under various and/or dynamic circumstances. Better understanding of the functioning of different aquatic ecosystems may enable proper conservation and restoration for these snake species and their habitats
Rezultati nadzora nad gripom tokom pandemijske i postpandemijskih sezona u AP Vojvodini, Srbija
Get PDFIntroduction. Although influenza is longest and most studied infectious disease, to date, not much has been achieved in preventing and combating this disease. Many infectious diseases are now eliminated or significantly reduced, but only influenza remained epidemic and pandemic character. Influenza epidemics occur every year. Increase in number of patients occurs in early winter. Pandemics occur over long intervals of time and are caused by new subtypes of the influenza virus. Objective. To analyze the epidemiological characteristics of influenza through surveillance of influenza during 3 seasons of monitoring. Method. Data for the analysis were gathered from epidemiological surveillance of influenza through sentinel surveillance, virological surveillance and control of severe acute respiratory distress syndrome. Sentinel physician network consisted of doctors from the public sector, general practitioners, pediatricians, and specialists of emergency medicine and pulmonologists from intensive care units. Supervisors were experts from the Institute of Public Health of Vojvodina, Novi Sad. Samples from the patients (nasopharyngeal swabs) were tested by PCR in National Reference Laboratories (Institute of Virology, Vaccines and Sera 'Torlak' in Belgrade) and in Institute of Public Health of Vojvodina). Results. During the pandemic season, based on the recorded incidence or intensity of clinical activity, incidence rate of the influenza virus infections was above the intermediate threshold (246.3) for the territory of Vojvodina in the period from 45th to 52nd week of surveillance with the peak incidence at 50th week (1090.3 / 100,000). In the next two seasons of sentinel surveillance intensity of virus activity threshold was above the average over the period of 4 to 10 weeks (season 2010/11) and of 11 to 13 weeks of surveillance (season 2011/12). The largest number of patients was registered in the age group of 5-14 years, and the lowest number of patients was in age group over 65. Summarized results of virological surveillance of influenza show that during the pandemic season the most frequent isolate was the virus influenza A (H1N1). The largest number (24) of confirmed cases was registered in 51st week of surveillance, which coincided with the highest activity of the virus influenza during sentinel surveillance of ILI. Within virological surveillance in the season 2010/11 out of total of 213 tested samples of patient material, infection was confirmed in 112 samples: influenza A (H1N1) was confirmed in 90% (101/112), type B in 6.3% (7/112) and influenza A (H3N2) in 3.6% (4/112) samples. During the last season dominant infection was influenza A (H3N2) with a share of 96.5% (55/57) of all confirmed cases of sentinel and non-sentinel specimens tested. The average age of the 38 patients with fatal outcome during the seasons 2009/10 and 2010/11 was 47.1 (range: 12 to 76 years), and all were confirmed to infection with influenza virus A (H1N1). Obesity had the largest share as a factor of comorbidity, and was registered in 36.8% (14/38) patients with fatal outcome. Conclusion. The influenza virus is constantly present in a population with different intensity from year to year. Disease is the most often registered in the preschool and school children, but fatalities due to influenza are usually registered among the working population.Uvod. Iako je influenca najduže i najviše izučavana zarazna bolest, do danas se nije mnogo postiglo u sprečavanju i suzbijanju ovog oboljenja. Mnoge zarazne bolesti su danas eliminisane ili je njihovo javljanje značajno smanjeno, ali je influenca zadržala epidemijski i pandemijski karakter. Epidemije influence se javljaju svake godine. U zemljama severne hemisfere epidemije imaju sezonski karakter. Porast broja obolelih je superponiran, odnosno poklapa se sa početkom zimskog perioda. Pandemije se javljaju u dužim vremenskim intervalima i uzrokovane su novim podtipovima virusa. Cilj rada. Analizirati epidemiološke karakteristike influence kroz nadzor nad gripom tokom tri sezone praćenja. Metod. Podaci za analizu potiču iz epidemiološkog nadzora nad gripom kroz predostrožni (sentinel) nadzor, virusološki nadzor i nadzor nad teškim akutnim respiratornim distres sindromom. Mrežu sentinel lekara činili su lekari iz državnog sektora, lekari opšte medicine i pedijatri, a u jedinicima intenzivne terapije specijalisti urgentne medicine i pulmolozi. Koordinatori nadzora su bili stručnjaci Instituta za javno zdravlje Vojvodine, Novi Sad. Rezultati. U AP Vojvodini, tokom pandemijske godine nadzora nad gripom, stopa incidencije je iznad srednjeg praga intenziteta u periodu od 45. nedelje tekuće godine do 1. nedelje naredne godine, dok su u postpandemijskom periodu vrednosti stopa incidencije iznad praga srednjeg intenziteta u periodu od 1. do 11. nedelje (sezona 2010/2011), odnosno od 11. do 14. nedelje (sezona 2011/2012) nadzora. Tokom pandemijske i naredne godine u uzorcima bolesničkog materijala (bris grla/nosa) dominira infekcija virusom gripa tip A podtip H1N1, a u sezoni 2011/2012 infekcija virusom gripa tip A podtip H3N2. Tokom pandemijske godine ukupan broj umrlih je 32, a tokom naredne sezone 6, dok u poslednjoj sezoni nadzora nisu registrovani smrtni ishodi od gripa. Najveće procentualno učešće umrlih je u uzrastu od 40 do 59 godina i iznosi 55,3% (21/38). Zaključak. Virus influence je konstantno prisutan u populaciji, s različitim intenzitetom aktivnosti od godine do godine. Oboljenje se najčešće registruje u predškolskom i školskom uzrastu, ali su smrtni ishodi zbog gripa najčešće registrovani među radno aktivnim stanovništvom
Influenza vaccine and learning in C57BL mice with an acute experimental autoimmune encephalomyelitis
No full textLiterature data suggest possible link between influenza vaccination and development of autoimmune processes. Therefore, the aim of the study was to investigate the effect of influenza vaccination on spatial learning in mice with experimental autoimmune encephalomyelitis (EAE). EAE was induced in eight-week-old C57BL/6J female mice by subcutaneous immunization (MOG(35-55) in complete Freund's adjuvant) and Pertussis vaccine injected intraperitoneally. Mice were vaccinated with influenza vaccine three days before MOG immunization. The hippocampal-dependent spatial learning test, Morris Water Maze test (MWM), was performed before and after EAE induction. Significant difference (P lt 0.05) in the time for completing the Morris Water Maze task was found between mice with mild clinical signs of EAE when compared to other mice. However no significant difference was observed between mice with EAE and mice with EAE that were vaccinated with influenza vaccine. Hippocampal tissue lesions in EAE mice are in correlation with memory impairment. Study shows no influence of influenza vaccine on progression of clinical signs of EAE, spatial learning and memory impairment