983 research outputs found
Sort by
Veza cirkulišućeg nivoa sklerostina sa markerima metabolizma kostiju kod pacijenata sa poremećajem rada štitaste žlezde
Get PDFBackground: The aim of this study was to compare serum sclerostin concentrations in patients with thyroid dysfunction with euthyroid control subjects and to assess the relationship between sclerostin and markers of bone metabolism (osteocalcin and beta-cross-laps). Methods: The study included 30 patients with thyroid dysfunction (hypothyroidism, hyperthyroidism and subclinical hyperthyroidism) and ten euthyroid controls. Free thyroxine (FT4) was measured by radioimmunoassay, while thyroid stimulating hormone (TSH) concentration was determined immunoradiometrically. We used an ELISA kit to determine the sclerostin level. The electrochemiluminescence method was applied for measuring the bone markers. Results: Sclerostin levels were significantly lower in hypothyroid patients (p=0.009) and significantly elevated in hyperthyroid patients (p=0.008) compared to control values. Hyperthyroid patients also had higher sclerostin than patients with subclinical hyperthyroidism (p=0.013). Sclerostin concentrations were negatively correlated with TSH levels (r=-0.746, p lt 0.001), but positively with FT4 (r=0.696, p lt 0.001). Moreover, sclerostin was positively associated with osteocalcin (r=0.605, p=0.005) and beta-cross-laps levels (r=0.573, p=0.008) in all thyroid patients. Conclusions: Serum sclerostin is significantly affected in subjects with thyroid dysfunction. Both sclerostin and thyroid status affect bone homeostasis, which is reflected through the significant correlations with osteocalcin and beta-cross-laps.Uvod: Cilj ove studije bio je da uporedimo serumske koncentracije sklerostina kod pacijenata sa disfunkcijom štitaste žlezde u odnosu na eutiroidne kontrolne ispitanike, i da procenimo odnos između sklerostina i markera koštanog metabolizma (osteokalcina i beta-cross-lapsa) u istoj populaciji. Metode: Studijom je obuhvaćeno 30 pacijenata sa disfunkcijom štitaste žlezde (hipotireozom, hipertireozom i supkliničkom hipertireozom) i 10 eutiroidnih kontrola. Slobodni tiroksin (FT4) meren je radioimunološkom metodom, dok je koncentracija tireostimulišućeg hormona (TSH) određivana imunoradiometrijski. Za merenje nivoa sklerostina koristili smo ELISA-test. Metoda elektrohemiluminiscencije primenjena je za merenje koncentracije koštanih markera. Rezultati: Nivo sklerostina bio je značajno niži kod bolesnika sa hipotireozom (p = 0,009) odnosno značajno viši kod bolesnika sa hipertireozom (p = 0,008) u poređenju sa vrednostima kod eutiroidnih kontrolnih ispitanika. Pacijenti sa hipertireozom su takođe imali statistički značajno viši nivo sklerostina u odnosu na bolesnike sa supkliničkom hipertireozom (p = 0,013). Pokazana je negativna korelacija koncentracije sklerostina i TSH (r = -0,746, p lt 0,001), odnosno pozitivna korelacija sa FT4 (r = 0,696, p lt 0,001) kod pacijenata sa tireoidnom disfunkcijom. Štaviše, sklerostin pozitivno korelira sa koncentracijom osteokalcina (r = 0,605, p = 0,005) i beta-cross-lapsa (r = 0,573, p = 0,008) kod ovih pacijenata. Zaključak: Serumski nivoi sklerostina izmenjeni su kod osoba sa disfunkcijom štitaste žlezde. Sklerostin zajedno sa tireoidnim statusom utiče na koštani metabolizam, što se ogleda u njegovoj značajnoj korelaciji sa osteokalcinom i beta-cross-lapsom
Supplementary information for the article: Stevanovic, G.; Obradovic, A.; Ristic, S.; Petrovic, D.; Milenkovic, B.; Mitrovic, D.; Vignjevic, S. F.; Ilic, K.; Stoiljkovic, V.; Lavadinovic, L.; Pelemis, M.; Petrovic, S.; Vidmanic, A.; Popovic, O.; Eremic, N.; Sparrow, E.; Torelli, G.; Socquet, M.; Holt, R.; Ilieva-Borisova, Y.; Tang, Y.; Scorza, F. B.; Flores, J.; Rathi, N. Safety and Immunogenicity of a Seasonal Trivalent Inactivated Split Influenza Vaccine: A Double Blind, Phase III Randomized Clinical Trial in Healthy Serbian Adults. Therapeutic Advances in Vaccines and Immunotherapy 2020, 8, 2515135520925336. https://doi.org/10.1177/2515135520925336
Get PDFSupplementary Table 1: Trial Scheme - Schedule of events for each participant; Supplementary Table 2: Details of Ethics committee/Institutional Review Board Overseeing the study;Supplementary material for: [https://doi.org/10.1177/2515135520925336]Related to the published version: [http://intor.torlakinstitut.com/handle/123456789/616
Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults
Get PDFThis study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2–95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains., ClinicalTrials.gov identifier: NCT02935192, October 17, 2016Supplementary information: [https://hdl.handle.net/21.15107/rcub_intor_637
Burkholderia cepacia YtnP and Y2-aiiA lactonases inhibit virulence of Pseudomonas aeruginosa via quorum quenching activity
No full textBurkholderia cepacia is well known as the causative agent of infections in humans where often shares niche with other pathogens, like Pseudomonas aeruginosa. Clinical isolate Burkholderia sp. BCC4135 was selected due to its strong quorum quenching (QQ) activity. Whole genome sequencing unveiled this isolate as B. cepacia with unique sequence type ST1485 and a myriad of genes belonging to resistome and virulome. Two QQ lactonases YtnP and Y2-aiiA originated from B. cepacia BCC4135 were cloned, expressed, and functionally characterized. They were active against a broad substrate spectrum of the N-acyl-homoserine lactones (AHLs). The YtnP lactonase was inactive, while Y2-aiiA was active against N-tetradecanoyl-DL-homoserine lactone (C14-HSL) which could imply the difference in their biological roles from the aspect of its quorum sensing (QS) autoregulation and interference with the QS systems of bacteria residing within the same niche. Both YtnP and Y2-aiiA were able to attenuate virulence potential of P. aeruginosa MMA83 clinical isolate declining its biofilm formation and virulence factors production. B. cepacia BCC4135 lactonases interfered with the las, rhl, and even pqs QS circuit of P. aeruginosa MMA83 transcription and the effect of combined enzymes was even more prominent. B. cepacia BCC4135 also employs the CepI/R QS system for governing its own virulence traits and possibly self-regulates the QQ/QS network through the different expression and activity of YtnP and/or Y2-aiiA. Our findings pointed out that BCC4135 lactonases could be exploited as an effective antivirulence drugs against P. aeruginosa and gave us a new insight into B. cepacia QQ/QS machinery
Beneficial heterologous effects of a tetanus vaccination: the role of molecular mimicry and/or trained immunity
No full textInfluence of aging on germinal centre reaction and antibody response to inactivated influenza virus antigens in mice: sex-based differences
No full textThe study examined sex-specificities in age-related changes in BALB/c mice IgG antibody responses to immunisation with trivalent inactivated split-virus influenza bulk. Aging diminished the total serum IgG antibody responses to H1N1 and H3N2 and B influenza virus antigens in mice of both sexes, but they remained greater in aged females. This sex difference in aged mice correlated with the greater post-immunisation increase in the frequency of spleen germinal centre (GC) B cells and more favourable T follicular regulatory (Tfr)/GC B cell ratio, as Tfr cells are suggested to control antibody production through suppression of glycolysis. The greater post-immunisation GC B cell response in aged females compared with males correlated with the greater proliferation of B cells and CD4+ cells in splenocyte cultures from aged females restimulated with inactivated split-virus influenza from the bulk. To support the greater post-immunisation increase in the frequency GC B cell in aged females was more favourable Tfr/T follicular helper (Tfh) cell ratio. Additionally, compared with aged males, in age-matched females the greater avidity of serum IgG antibodies was found. However, in aged females IgG2a/IgG1 antibody ratio, reflecting spleen Th1/Th2 cytokine balance, was shifted towards IgG1 when compared with age-matched male mice. This shift was ascribed to a more prominent decline in the titres of functionally important IgG2a antibodies in females with aging. The study suggest that biological sex should be considered as a variable in designing strategies to manipulate with immune outcome of immunisation in aged animals, and possibly, at very long distance, humans
In- depth quantitative profiling of post- translational modifications of Timothy grass pollen allergome in relation to environmental pollution and oxidative stress
No full textProbiotic activity and microencapsulation of Lactobacillus reuteri b2 isolated from feces of c57bl/6 mice
No full textThe major parts of the commensal microbial flora of the human gastrointestinal tract (GIT)
belong to the lactic acid bacteria (LAB) that are frequently used as probiotics. Probiotics must
survive passage through the upper GIT and reach its site of action alive, where they have to
maintain their stability, viability and function. Preparation of various biopolymer-based carriers
and microencapsulation become inevitable part of probiotics-focused researches. In this study,
we assessed probiotic activity of Lactobacillus reuteri B2 selected from the panel of LAB
isolated from the feces of C57BL/6 mice. L. reuteri B2 was evaluated as potential probiotic and
its microencapsulation with alginate-based materials were performed. We hypothesized that if L.
reuteri B2 in the free form can survive all conditions in the GIT then the usage of the appropriate
biomaterials for microencapsulation would improve its viability and stability in GIT.
Consequently, there has been assessed L. reuteri B2 in free and in microencapsulated form, in
vitro, in the culture of epithelial cells. High survival rate of L. reuteri B2 at low pH (2.0- 4.0)
and in the presence of the bile salts at concentrations up to 0.30% imply that it can survive harsh
conditions within GIT. Likewise, L. reuteri B2 strong antimicrobial activity toward pathogen
species on which this strain has been assessed. Furthermore, testing of the alginate-based
polymers revealed no negative impact on the viability of epithelial cells. Results obtained from
this study highly encourage further research on the impact of alginate- encapsulated L. reuteri
B2 in physiological conditions as well as for the prevention or treatment of some pathological
states. Additionally, demonstrating extended viability of encapsulated probiotics in vivo will
justify scaling up the encapsulation process for commercial application
Prophylactic treatment by banana lectin influences the immune response in the peak of experimental colitis
No full textBanana is highly abundant in everyday nutrition and it is recommended to be a part of
the diet with patients suffering from inflammatory bowel diseases. A mannose-specific
banana lectin (BanLec) is reported to be a potent immunomodulator. Our aim was to
explore the prophylactic impact of BanLec in a murine model of colitis. A recombinant
BanLec (rBanLec) that possesses structural and functional characteristics similar to
naturally occurring counterparts was used in the research. Colitis was induced (day 0)
in C57BL/6 mice by 2,4,6-trinitrobenzene sulfonic acid (TNBS; 3.5 mg/ml TNBS /
50% ethanol, 100 μl intrarectal). 24h prior to the induction of colitis, mice were treated
(100 μl, intrarectal) by 0.1 μg/ml (rBL0.1), 1 μg/ml (rBL1) and 10 μg/ml (rBL10)
rBanLec/PBS. Mice subjected to colitis induction without rBanLec pretreatment (PC)
were referent. The impact of rBanLec pretreatment was assessed at the peak of the
disease (day 2). Body weight loss was taken as a main parameter for estimation of
disease severity. A significant reduction in disease severity was noticed in rBL0.1
group and it correlated with lower leukocyte infiltrations in the colon. Nevertheless,
inflammation-related parameters (MPO activity, production of NO, IL-12 and TNFα)
were significantly lower in colons of rBL0.1 group compared to rBL1, rBL10 and PC
groups. Levels of regulatory cytokines (IL-10, TGFβ) were the highest in the colons of
rBL0.1 group. Local activities of antioxidant enzymes (CAT, SOD, GST) were also
significantly increased in rBanLec-pretreated groups, especially in rBL0.1 group.
Presented results show that local stimulation by low dose of rBanLec prior to colitis
induction reduces the severity of the disease. Observed positive impact resulted from
the stimulation of local regulatory and antioxidant mechanisms that alleviate harmful
proinflammatory response. (Supported by Ministry of Education, Science and
Technological Development Republic of Serbia, Grant no. 172049
Digestomics of raw and roasted hazelnut according to Infogest protocol and characterization of gastric-phase products
Get PDFBrief introduction: Stability to gastric digestion represents a very important parameter of food protein allergenicity. Usually digestion experiments are carried out on purified proteins or protein extracts; however, use of solid food is far closer to the in vivo situation, taking into account food protein interactions with other food components, such as polyphenols and lipids.Objective: The aim of this study was to investigate and compare digestion stability and allergenicity of large and small peptides released after pepsin digestion of whole raw and roasted hazelnut kernels under standardized and physiologically relevant in vitro conditions.Methodology: In vitro simulated oral and gastric phase digestion was carried out with ground raw and roasted hazelnut kernels. Digested proteins were extracted from the mixture and analyzed by SDS-PAGE, 2D-PAGE, and compared with Image Master 2D Platinum 7.0. Western blot probed with allergic patients’ sera and specific antibodies for Cor a 8.Main findings: Several important hazelnut seed storage digestion resistant proteins and peptides have been identified and characterized. Most abundant hazelnut allergens were resolved on a 2DE map, for instance acidic and basic chains of Cor a 9, and Cor a11. Digestion-resistant peptides of Cor a 11 and Cor a 9 were able to bind IgE. Lipid transfer protein (Cor a 8) was highly resistant to gastric proteolysis. Conclusion: To conclude, roasted hazelnut is more prone to gastric digestion than raw, and cause milder IgE response in patients. Gastric phase digestion of raw and roasted hazelnut kernels results in partial extraction and digestion of Cor a 11 and Cor a 9 into digestion- resistant peptides with preserved IgE-binding epitopes. These results demonstrate substantial resistance of raw and roasted hazelnut allergens to gastric digestion since they remained mostly intact after 2 h of gastric (pepsin) digestion and retained their allergenicity