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Immunoreactive neuropeptides in the cells of human thymus
The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall's corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans
Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers
Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenstrom's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs
Uloga mast ćelija u inflamaciji šape i dva inbredna soja pacova, Dark Agouti i Albino Oxford
Na modelu akutne inflamacije šape indukovane intraplantarnim ubrizgavanjem
konkanavalina A (engl., Concanavalin A, Con A) kod pacova
pokazali smo sojne razlike u pogledu intenziteta i kinetike inflamatorne
reakcije, pri čemu su Dark Agouti (DA) pacovi razvijali jači
odgovor u odnosu na Albino Oxford (AO) pacove. Cilj ovog rada Je bio
da se utvrdi da li medijatori mastocita doprinose sojnim razlikama u
inflamaciji šape kod DA i AO pacova. Sistemska deplecija mastocita
Je izvršena sukcesivnim |. p. tretmanom rastućim dozama supstance
48/80, а ınflamacija Je indukovana 24 sata nakon poslednjeg tretmana.
Rezultati su pokazali da prethodna deplecija mastocita potencira inflamaciju
kod DA pacova tako što povećava dijametar ınflamirane šape
(meren nonijusom) | ekstravazaciju plazme (određivana metodom sa
Evans blue), ali smanjuje influks granulocita (određivan merenjem mi-
Jeloperoksidazne aktivnosti) u odnosu na kontrolne Životinje. Nasuprot
tome, kod AO pacova deplecija mastocita dovodi do supresije svih
parametara ınflamacije. Ispitivanjem fenotipa mononuklearnih ćelija
izolovanih iz inflamiranog tkiva šape u piku ınflamacije potvrđeno Je
smanjenje procenta HIS48* granulocita usled deplecije mastocita u
oba soja pacova. Takođe, tretman sa 48/80 povećava procenat ED2?
makrofaga u drenirajućim limfnim čvorovima AO ı DA pacova, а! | zastupljenost
ED2* makrofaga u tkivu inflamiranin Sapa kod AO pacova
Rezultati ukazuju da su medijatorı mastocita neophodni za razvoj ınflamatornog
edema Sape | ekstravazacyu plazme u AO, ali ne ı u DA
pacova. dok su u oba soja pacova mediator mastocita neophodni za
regrutaciju ćelija u ınflamatorni fokus ı remodelovanje ćelijskog miljea
drenirajućih limfnih čvorova u ınflamaciji
Induction of APS after TTd Hyper-Immunization has a Different Outcome in BALB/c and C57BL/6 Mice
Problem The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy complications (lower fecundity and lower litter size), as well as by an increase in anti-beta(2) glycoprotein I (beta(2)GPI)-specific autoantibody titer. We have investigated how the genetic background of the immune system [T helper (Th) prevalence] and the type of animal model of APS influence the induced pathology. Method of Study Antiphospholipid syndrome induced by tetanus toxoid (TTd) hyper-immunization and by intravenous application of monoclonal anti-beta(2)GPI-specific antibody 26 was compared in C57BL/6 (Th1 prone) and BALB/c (Th2 prone) mice. Results Tetanus toxoid hyper-immunization of BALB/c mice led to reduction in fertility, but in C57BL/6 mice a decrease in fecundity occurred. In both cases, pathology was caused by anti-beta(2)GPI antibodies, the production of which was adjuvant and strain dependent. Conclusion We conclude that TTd immunization and i.v. application of monoclonal antibody 26 induced the same reproductive pathology and that the type of pathology is strain dependent
Arbovirusi kod nas i u svetu
Arboviruses are the most numerous group of viruses with 534 registered members. With a few exceptions, most of arboviruses are RNA viruses. Mostly they have zoonotic characteristics and are transmissible by vectors- arthropods (ticks, mosquitoes, phlebothomines etc.) on human and animal population. Arboviruses induced epidemics and epizooties have massive occurrence with huge economic loses. Primarily, arboviruses are neurotropic viruses that cause damage on central nervous system with lethality rate 5-80%, and are considered to be very dangerous- biohazard. Beside vector transmission interhuman transmission can occur (Crimean-Congo hemorrhagic fever, Ebola, Lasso, Marburg). According to their characteristics, some of arboviruses took place in the List of biological weapons used against humans, animals and even plants. Investigation of Arboviruses in the Republic of Serbia has been started in 1960s, resulting with isolation of 5 arboviruses - 4 were isolated from vectors samples and one from human material sample. Two of them under the name of Jug Bogdanovac and Dubrava/Belgrade took place in the International catalogue of viruses as a new isolated arboviruses. The formation of distribution map of Arboviruses in Serbia was started by isolations and seroepidemiological investigations as well as overview of their impact to human public and veterinary medicine health.Arbovirusi su najbrojnija grupa virusa sa više od 534 registrovana člana. Sa malim izuzetkom to su RNK virusi. Većina su zoonoznog karaktera, a na ljude i životinje prenose se posredstvom artropoda (krpelja, komaraca, flebotomina). Epidemije i epizootije koje izazivaju su masovne sa velikim ekonomskim gubicima u zdravstvu i ekonomiji zemlje. Primarno su neurotropni i izazivaju oštećenja centralnog nervnog sistema sa letalitetom od 5-80%. Neki su veoma opasni - biohazardni i pored vektorskog prenošenja prenose se i intrahumano (Krimska - Kongo HG, Ebola, Lassa, Marburg i druge). Zbog svojih osobina neki arbovirusi su i na listi biološkog oružja protiv ljudi, životinja, pa čak i bilja. Istraživanja arbovirusa u Srbiji započeta su 1960 godine, a rezultirala su izolacijom 5 arbovirusa i to 4 iz vektora (Krpelja, komaraca i flebotomina), od kojih je jedan kao nov pod imenom Jug Bogdanovac ušao u međunarodni katalog, i jedan iz humanog materijala koji je pod imenom Dobrava/Belgrade takođe registrovan u međunarodnom katalogu arbovirusa. Izolacijama virusa i seroepidemiološkim istraživanjima započeto je formiranje karte rasprostranjenosti arbovirusa u Srbiji i sagledavanje njihove uloge u zdravstvu i veterinarskoj medicine
Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome
The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field
Razlike u edemu šape pacova indukovanom konkanavalinom a u zavisnosti od soja - uticaj histaminskih H1 i H2 receptora
The present study tests the hypothesis that the difference in the intensity of paw edema found between the Dark Agouti (DA) and Albino Oxford (AO) rat strains originates from the distinct participation of histamine, serotonin and their corresponding receptors in Concanavalin A (Con A)-induced inflammation. DA and AO male rats were intraplantarly injected with specific receptor antagonists prior to Con A, and the intensity of inflammation was determined by measuring the paw diameter. Our results have showed that histamine H1 and H2 receptor antagonists reduced the Con A-induced paw edema in DA rats, while serotonin 5HT3 receptor antagonist diminished the inflammation in both DA and AO rat strains. The calcium channel blocker did not change Con A-induced inflammation. Strain differences in the intensity and kinetics of inflammation observed between the DA and AO rats are most likely defined by the diversity of mediators released and their receptors activated upon Con A injection.Testirana je hipoteza da razlike u intenzitetu inflamatornog edema šape indukovanog konkanavalinom A u pacova Dark Agouti (DA) i Albino Oxford (AO) soja potiču od različitog doprinosa histamina i serotonina i njihovih odgovarajućih receptora. Mužjaci pacova DA i AO soja su intraplantarno tretirani antagonistima specifičnih receptora pre izazivanja inflamacije konkanavalinom A i intenzitet inflamacije je praćen merenjem dijametra šape. Naši rezultati su ukazali da antagonisti histaminskih H1 i H2 receptora smanjuju edem šape indukovan konkanavalinom A u DA pacova, dok antagonist serotoninskih 5HT3 receptora smanjuje edem šape u oba soja pacova. Blokator kalcijumskih kanala ne utiče na inflamaciju izazvanu konkanavalinom A. Razlike u intenzitetu i kinetici inflamatornog odgovora indukovanog konkanavalinom A između DA i AO sojeva su najverovatnije posledica razlika u oslobođ enim medijatorima i aktivaciji odgovarajućih receptora nakon injekcije konkanavalina A
Hexameric immunoglobulin M in humans: Desired or unwanted?
Immunoglobulin M (IgM) is the first antibody produced upon infection, and is often suggested as the first line of defense of human immune system. In addition to being present on the surface of naive B cells as a monomeric molecule, IgM is always secreted as a polymer. The most abundant IgM polymer in humans is pentamer, composed of five monomeric units, joined together by so-called joining on chain. On the other hand, it is well known that hexameric IgM can be also found in human sera. Its presence is often related to different dissorders (Waldenstrom's macroglobulinemia, cold agglutinin, and recurrent urinary bacterial infections), although it is believed that small amounts of hexamer are present in normal human sera as well. Unlike pentamer, IgM hexamer contains six monomeric blocks and completely lacks J chain. Although it has been decades since its discovery, the precise function of IgM hexamer is still unknown. Since it was documented that hexamer is very potent in activating complement, it is suggested that its production in humans must be under strict control, and that it is produced in special conditions, when strong activation of complement is absolutely needed. However, the question is whether hexameric IgM is really a secret weapon or just an undesirable molecule in humans. According to structural and known functional characteristics of both pentamers and hexamers of IgM, it can be concluded that hexamers are, in addition to being maybe too reactive to be around, probably not that efficient in protecting us from bacterial and viral infections. (C) 2011 Elsevier Ltd. All rights reserved
Emergence of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in a paediatric hospital in Serbia
Molecular detection and surveillance of theresistance genes harboured byPseudomonas aeruginosa are becomingincreasingly important in assessing andcontrolling spread and colonization inhospitals, and in guiding the antibiotictreatment of infections. Metallo-blactamase (MBL)-producing P. aeruginosastrains are slowly but steadily increasingwithin hospitals, causing outbreaks and/orhyperendemic situations in some centres,mostly in the Far East and the south ofEurope (Queenan & Bush, 2007). Theglobal dissemination of MBL-producingP. aeruginosa strains has also reached theBalkan region (Lepsanovic et al., 2008;Sardelic et al., 2003). The objective of ourstudy was to detect and characterize P.aeruginosa isolates producing MBLs fromthe 400-bed paediatric tertiary carehospital Mother and Child Health Instituteof Serbia ‘Dr Vukan Cupic