37 research outputs found
Funkcija Ŕtitaste žlezde i prisustvo antitireoidnih autoantitela kod bolesnika sa sistemskim bolestima vezivnog tkiva
Autoimmune thyroid disease (ATD) has been described in patients with connective tissue diseases (CTD). The aim of this study was to estimate and compare the prevalence of ATD in a group of 91 CTD patients, and in their subgroups: 53 systemic lupus erythematosus (SLE), 24 rheumatoid arthritis (RA), 7 primary Sjogrenās syndrome (SSy) and 7 progressive systemic sclerosis (SSc) patients. A control group of 34 healthy blood volunteers was used for comparison. Serum levels of free thyroxine (FT4), thyroid stimulating hormone (TSH), as well as thyroid autoantibodies (Abs) specific of thyroperoxidase (TPO) and thyroglobulin (TG) were examined. CTD patients, in general, as well as SLE and RA subgroups, had significantly higher number of thyroid dysfunction than the control group (p lt 0.05). The most prominent thyroid dysfunction was subclinical hypothyroidism, with a higher prevalence in all subgroups of patients when compared to the control. Anti-TPO Abs were detected in a significant number of CTD patients, especially in SLE subgroup when compared to the control group. It was also found that a higher number of CTD patients, SLE and RA subgroups, had positive anti-Tg Abs, when compared to the control subjects. In conclusion, the prevalence of ATD in CTD patients was more frequent than in the control group. The patients with anti-TPO Abs and anti-Tg Abs at the time when they were analyzed, had hyperthyroidism, hypothyroidism or were clinically and biochemically euthyroid. The prevalence of hypothyroidism was greater than the prevalence of hyperthyroidism in all subgroups of patients.Autoimunske bolesti Å”titaste žlezde (AITD) opisane su kod bolesnika sa sistemskim bolestima vezivnog tkiva (SBVT). Cilj ovog rada bio je da se ispita prevalencija AITD u grupi od 91 bolesnika sa SBVT, koja je ukljuÄila 53 bolesnika sa sistemskim eritemskim lupusom (SLE), 24 obolelih sa reumatoidnim artritisom (RA) i po 7 obolelih od primarnog Sjogrenovog sindroma (SSy) i progresivne sistemske skleroze (SSc). Kontrolnu grupu ispitanika Äinila su 34 dobrovoljna davaoca krvi. Kod svih uÄesnika u studiji merene su serumske koncentracije slobodnog tiroksina (FT4), tireostimuliÅ”uÄeg hormona (TSH), kao i autoantitela specifiÄnih za tireoperoksidazu (anti-TPO At) i tireoglobulin (anti-Tg At). U grupi bolesnika sa SBVT, kao i u podgrupama obolelih od SLE i RA, naÄena je statistiÄki znaÄajno veÄa uÄestalost poremeÄaja funkcije Å”titaste žlezde u odnosu na kontrolnu grupu (p lt 0.05), a od svih poremeÄaja funkcije Å”titaste žlezde najÄeÄÄe je detektovana subkliniÄka hipotireoza. Anti-TPO At naÄena su kod znaÄajno veÄeg broja bolesnika sa SBVT i SLE, u odnosu na kontrolnu grupu. Isto tako, i anti-Tg At su detektovana kod veÄeg broja ispitanika u grupi SBVT, i podgrupama SLE i RA, nego kod zdravih osoba. U zakljuÄku, prevalencija AITD kod obolelih od SBVT veÄa je nego u kontrolnoj grupi. Bolesnici sa anti- TPO At i anti-Tg At u vreme kada su analizirani, imali su subkliniÄku ili kliniÄki manifestnu hipotireozu ili hipertireozu, ili su joÅ” bili u stadijumu bolesti u kome se ne može detektovati poremeÄaj funkcije Å”titaste žlezde. Prevalencija hipotireoze bila je veÄa od prevalencije hipertireoze u svim podgrupama bolesnika sa SBVT
Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides
Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (Ī±1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low Ī±1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease
Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis (vol 49, pg 598, 2022)
J Rheumatol 2022; doi: 10.3899/jrheum.210931
In the Methods section, under the subheading āFollow-up and study outcome,ā the last sentence should be as follows: āAll new DUs were recorded by contacting all 39 patients once every 1ā3 months during follow-up.ā The error does not affect the results or conclusions of the study.
This correction only applies to the April 1 First Release. The correct text appears in the print and online issues
Influence of promoter polymorphisms of the TNF-Ī± (-308G/A) and IL-6 (-174G/C) genes on therapeutic response to etanercept in rheumatoid arthritis
Uvod: GenetiÄki faktori su znaÄajni za predviÄanje ishoda leÄenja bolesnika sa reumatoidnim artritisom (RA). Cilj studije bio je da se ispita uticaj-308G/A TNF-Ī± (rs 1800629) i -174G/C IL-6 (rs1800795) promotorskih polimorfizama na terapijski odgovor na etanercept. Metode: U studiju su bila ukljuÄena 73 pacijenta sa aktivnim RA. Terapijski odgovor je procenjivan posle 6 i 12 meseci terapije po kriterijumima Evropske lige protiv reumatizma. Genotipizacija pacijenata za polimorfizme -308G/A TNF-Ī± i -174G/C IL-6 uraÄena je PCR-RFLP metodom i procenjivan je uticaj genotipova na odgovor na etanercept. Rezultati: Nije bilo razlike u procentu respondera (pacijenti kod kojih se DAS28 popravio gt 1,2) izmeÄu pacijenata sa TNF-Ī± -308GG, GA i AA genotipom ni posle 6 ni posle 12 meseci tretmana. Posle 12 meseci leÄenja procenat respondera je bio znaÄajno veÄi kod pacijenata sa IL-6 -174GG u odnosu na pacijente sa GC ili CC genotipom (p= 0,006, x2 test). PoreÄenje pacijenata prema kombinovanim IL-6/TNF-Ī± genotipovima pokazalo je da je IL-6 -174GG / TNF-Ī± -308GG genotip uÄestaliji kod respondera u odnosu na druge kombinovane genotipove (p= 0.022, x2 test). TaÄnije, svi pacijenti sa kombinovanim IL-6 -174GG / TNF-Ī± -308GG genotipom bili su responderi posle 12 meseci terapije etanerceptom. ZakljuÄak: Studija pokazuje da bolesnici sa genotipovima koji se povezuju sa manjom produkcijom TNF-Ī± i IL-6 najbolje odgovaraju na terapiju etanerceptom.Background: The study was undertaken to assess the influence of functional -308G /A TNF-Ī± (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-Ī± blocker, in patients with rheumatoid arthritis (RA). Methods: Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G /A TNF-Ī± and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed. Results: No difference in the percentage of responders (patients who had DAS28 improvement gt 1.2) between patients with the TNF-Ī± -308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/TNF-Ī± genotypes showed that patients with the IL-6 -174GG / TNF-Ī± -308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chisquare test). More precisely, all patients with the combined IL-6 -174GG / TNF-Ī± -308GG genotype were responders after 12 months of etanercept treatment. Conclusions: The study suggests that patients who are genetically low TNF-Ī± and IL-6 producers are the best responders to etanercept therapy
Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients
The function of immune complexes in rheumatoid arthritis (RA) is related to their composition and size. Using dynamic light scattering (DLS), we investigated the link between the RA circulating immune complex (CIC) particlesā size and the CIC immunoglobulin level. In this study, 30 RA patients and 30 healthy individuals were included. IgA, IgG, and IgM were found in all analyzed CICs, but more IgA and IgG were found in RA than in control CICs. In both control and RA CICs, DLS detected 50 particles that differed in size and clustered around two size groups: with a 7.5ā164 nm radius and with a 342ā1718 nm radius. An increased level of IgA in RA CICs, compared to control ones, was associated with more than 50% of CIC particles. In RA, compared to the control, a higher number of CICs with 28.2 nm, 531 nm, 712 nm, and 1718 nm particles and a lower number of CICs with 78.8 nm particles were detected. This particle distribution pattern did not reflect the changes in the CIC immunoglobulin level. Thus, RA elevated CIC IgA was linked with all these particles (except the 1718 nm particle), the IgM increase was linked with 43.8 nm and 712 nm particles, and the IgG increase was linked with the 712 nm particle only. This study provides the very first data on the association between CIC particlesā size, CIC immunoglobulin level, and RA. It opens the possibility that the size of CICs determined by DLS can be used as a criterion in RA diagnosis or monitoring after a large-scale study confirmation
Influence of Promoter Polymorphisms of the Tnf-Ī± (-308g/A) and IL-6 (-174g/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis
Background: The study was undertaken to assess the influence of functional -308G/A TNF-alpha (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-alpha. blocker, in patients with rheumatoid arthritis (RA). Methods: Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G/A TNF-alpha and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed. Results: No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-alpha -308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/INF-alpha genotypes showed that patients with the IL-6 -174GG / TNF-alpha -308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chi-square test). More precisely, all patients with the combined IL-6 -174GG / TNF-alpha -308GG genotype were responders after 12 months of etanercept treatment. Conclusions: The study suggests that patients who are genetically low TNF-alpha and IL-6 producers are the best responders to etanercept therapy
Comparative analysis of the prices of essential medicines among Bulgaria and Macedonia
The prices of medicines differ because of many reasons as the sector that is purchasing medicines, distribution channel, patent status, trade mark and methodology of pricing. The current study aims at comparing the manufactoring, wholesale and retail prices of 30 30 INN essential medicines in Bulgaria and Macedonia as well their affordability to the population. There are presented the results for amoxicillin and glibenclamid. The collection, verification and data analysis are following the new WHO approach for medicines prices comparison. For the 30 INN included in the WHO list are collected data for registered trade marks in both countries, and their prices are collected. The randomized sample of 4 regions in both countries were created at whole - sale and retail prices are observed for the selected INN. It is compared the prices of generic and branded products for each segment - manufactoring, wholesale and retail. The affordability of the population to the medicines necessary for the treatment of diabetes II and bronchopneumonia is calculated comparing the cost of monthly treatment and minimal governmental wages in both countries. The analysis of the ceiling prices calculated by the MoH in Bulgaria revealed that in order to increase affordability is necessary to negotiate prices mainly at manufactoring level. It is also necessary to consider the discounts that are provided within ceiling prices that made prices lower at consumer level and also change the price structure. The analysis show that the prices in both countries differ in significant extend but the existing price control mechanisms are effective and allow pepople affordability to important medicines
Gabriel GarcĆa MĆ”rquez in njegove prevajalke
Sodelovale so: Alenka Bole Vrabec, Vesna Velkovrh-Bukilica in Veronika Rot. Pogovor je moderirala Barbara Pregelj
Prosim, uvrstiti pod 3.26 (drugi dogodki
J.Serb.Chem.Soc. 67 (8ā9)567ā572(2002) UDC 577.153.004.12:582.998.2 JSCSā2977 Original scientific paper
Isolation and partial characterization of an acid phosphatas
Physicochemical and immunologic characterization of low molecular-weight allergoids of Dactylis glomerata pollen proteins
Background: Orchard grass (Dactylis glomerata) pollen proteins were chemically modified by means of acid anhydrides (maleic and succinic anhydride) to obtain low-molecular-weight allergoids. Chemical modification in both cases led to the replacement of one positive charge (epsilon amino group of Lys) by one negative charge, yielding proteins with changed physicochemical properties in comparison to the native orchard grass-pollen proteins. Methods: Physicochemical characterization of derivatives was done by gel chromatography, SDS-PAGE, and isoelectric focusing. To examine the IgE-binding properties of these derivatives, we carried out immunoblotting. To examine the ability of derivatives to induce IgG production, we immunized rabbits. Skin prick testing with the allergoids was performed on 15 individuals allergic to orchard grass pollens and on two healthy subjects. Results: II was shown that the modified proteins retain their original molecular weights, but change pi to more acidic values. In the case of allergoids, a strong reduction in IgE binding was found. Immunization of rabbits with allergoids showed that the derivatives retain the ability to induce IgG production, and that the antisera obtained in such a way react to native (unmodified) extract. The ability of derivatives to induce allergic reaction was significantly reduced. The patients (86.6%) included in our study exhibited less than 50% of native extract response. Among them, 53.3% had no response to one or both allergoids. Conclusions: These modification procedures yield allergoids with a reduced allergenic activity and preserved immunogenic potential suitable for use in immunotherapy