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  1. Article ; Online: Get reliable laboratory findings - how to recognize the deceptive effects of angiotensin-converting enzyme inhibitor therapy in the laboratory diagnostics of sarcoidosis?

    Szabó, Attila Ádám / Enyedi, Enikő Edit / Altorjay, István Tibor / Hajnal, Péter / Pintér, Tamás Bence / Mányiné, Ivetta Siket / Váradi, Csongor / Bányai, Emese / Tóth, Attila / Papp, Zoltán / Fagyas, Miklós

    Clinical chemistry and laboratory medicine

    2024  

    Abstract: Objectives: Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams ... ...

    Abstract Objectives: Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams by lowering ACE activity, delaying diagnosis and giving a false impression of disease activity of sarcoidosis. We aimed to develop a simple method to detect the presence of ACEi drugs in samples, to investigate the ACEi medication-caused interference and consequences in a retrospective study.
    Methods: ACE activity and the level of ACE inhibition were determined for 1823 patients with suspected sarcoidosis. These values were compared with the therapeutic information at the first and follow-up visits.
    Results: A total of 302 patients had biochemical evidence of an ACEi drug effect during diagnostic ACE activity testing. In their case, ACE activity was significantly lower (median(IQR): 4.41 U/L(2.93-6.72)) than in patients not taking ACEi (11.32 U/L(8.79-13.92), p<0.01). In 62 sarcoidosis patients, the ACEi reduced ACE activity to the reference range or below. Only in 40 % of the cases was the medication list recorded in the outpatient chart and only in 3 cases was low ACE activity associated with ACEi use. 67 % of the repeated ACE activity measurements were also performed during ACEi therapy.
    Conclusions: Our study revealed that the use of ACEi is common in patients with suspected sarcoidosis. The ACE activity lowering effect of ACEi drugs may escape the attention of medical teams which can lead to diagnostic errors and unnecessary tests. Nevertheless, these pitfalls can be avoided by using a method suggested by our team.
    Language English
    Publishing date 2024-01-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1418007-8
    ISSN 1437-4331 ; 1434-6621 ; 1437-8523
    ISSN (online) 1437-4331
    ISSN 1434-6621 ; 1437-8523
    DOI 10.1515/cclm-2023-1288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Case report: Complex evaluation of coagulation, fibrinolysis and inflammatory cytokines in a SARS-CoV-2 infected pregnant woman with fetal loss.

    Tóth, Eszter Lilla / Orbán-Kálmándi, Rita / Bagoly, Zsuzsa / Lóczi, Linda / Deli, Tamás / Török, Olga / Molnár, Sarolta / Baráth, Sándor / Singh, Parvind / Hevessy, Zsuzsanna / Katona, Éva / Fagyas, Miklós / Szabó, Attila Ádám / Molnár, Szabolcs / Krasznai, Zoárd Tibor

    Frontiers in immunology

    2024  Volume 15, Page(s) 1329236

    Abstract: Background: SARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn't been described so far. Besides knowledge gaps in the ... ...

    Abstract Background: SARS-CoV-2 infection during pregnancy increases the risk of severe obstetrical complications. Detailed evaluation of COVID-19-associated coagulopathy in a pregnancy with stillbirth hasn't been described so far. Besides knowledge gaps in the pathomechanism leading to stillbirth in COVID-19 pregnancies, currently, no prognostic biomarker is available to identify pregnant patients who are at imminent risk of COVID-19-associated maternal and fetal complications, requiring immediate medical attention.
    Case: Here we report the case of a 28-year-old SARS-CoV-2 infected pregnant patient, admitted to our hospital at 28 weeks of gestation with intrauterine fetal loss. The presence of SARS-CoV-2 placentitis was confirmed by immunohistological evaluation of the placenta. She had only mild upper respiratory symptoms and her vital signs were within reference throughout labor and postpartum. The stillborn infant was delivered per vias naturales. Fibrinogen concentrate was administered before and after labor due to markedly decreased fibrinogen levels (1.49 g/l) at admission and excessive bleeding during and after delivery. Although coagulation screening tests were not alarming at admission, the balance of hemostasis was strikingly distorted in the patient. As compared to healthy age- and gestational age-matched pregnant controls, increased D-dimer, low FVIII activity, low FXIII level, marked hypocoagulability as demonstrated by the thrombin generation assay, together with shortened clot lysis and decreased levels of fibrinolytic proteins were observed. These alterations most likely have contributed to the increased bleeding observed during labor and in the early postpartum period. Interestingly, at the same time, only moderately altered inflammatory cytokine levels were found at admission. Serum ACE2 activity did not differ in the patient from that of age- and gestational age-matched healthy controls, suggesting that despite previous speculations in the literature, ACE2 may not be used as a potential biomarker for the prediction of COVID-19 placentitis and threatening fetal loss in SARS-CoV-2-infected pregnancies.
    Conclusions: Although based on this case report no prognostic biomarker could be identified for use in pregnant patients with imminent risk of fetal loss associated with COVID-19 placentitis, the above-described hemostasis alterations warrant awareness of postpartum hemorrhagic complications and could be helpful to identify patients requiring intensified medical attention.
    MeSH term(s) Humans ; Female ; Infant ; Pregnancy ; Adult ; Fibrinolysis ; SARS-CoV-2 ; Cytokines ; Angiotensin-Converting Enzyme 2 ; Pregnant Women ; Stillbirth ; COVID-19/complications ; Chorioamnionitis ; Biomarkers ; Fibrinogen
    Chemical Substances Cytokines ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Biomarkers ; Fibrinogen (9001-32-5)
    Language English
    Publishing date 2024-02-21
    Publishing country Switzerland
    Document type Case Reports ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1329236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Effect of anti-SARS-CoV-2 BNT162b2 mRNA vaccination on thrombin generation in children with inflammatory bowel disease.

    Stercel, Vivien / Lóczi, Linda / Kadenczki, Orsolya / Nemes, Éva / Nagy, Béla / Hodossy-Takács, Rebeka / Szabó, Attila Ádám / Fagyas, Miklós / Kappelmayer, János / Szabó, Tamás / Bagoly, Zsuzsa

    Frontiers in immunology

    2023  Volume 14, Page(s) 1257072

    Abstract: Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. Despite encouraging data reporting vaccine safety and ... ...

    Abstract Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. Despite encouraging data reporting vaccine safety and low IBD flare rates in adults with IBD, vaccine hesitancy was demonstrated to be high in families of children with IBD. We aimed to find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV-2 mRNA vaccination.
    Patients and methods: In this observational case-control study, 38 children with IBD (CD:18, UC: 20) aged 12-18 years and 62 healthy age-and sex-matched children were enrolled. Blood was collected before the first dose and 2-6 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine dose. Blood cell counts, fibrinogen, inflammatory markers (hsCRP, ferritin), anti-SARS-CoV-2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Detailed clinical parameters including disease activity scores (PUCAI, PCDAI) were registered pre-and post- vaccination. A guided questionnaire was used to collect data on adverse reactions (AEs) post- vaccination.
    Results: Baseline TG parameters did not differ between patients and controls. Endogenous thrombin potential showed a significant positive correlation with markers of inflammation and with PCDAI. Inflammatory parameters and TG did not increase in patients and controls post-vaccination. Vaccination significantly increased antibody levels in all three investigated groups, but post-vaccination anti-SARS-CoV-2 S IgG/IgM levels were below the 5
    Conclusion: Our study is the first to support the safety and efficacy of anti-SARS-CoV-2 BNT162b2 vaccination in children with IBD with detailed pre-and post-vaccination laboratory data including TG. Results of this study may further increase confidence and reduce vaccine hesitancy in caretakers of pediatric IBD patients.
    MeSH term(s) Child ; Humans ; Antibodies, Viral ; BNT162 Vaccine ; Case-Control Studies ; Colitis, Ulcerative ; COVID-19/prevention & control ; Crohn Disease ; Immunoglobulin G ; Immunoglobulin M ; Inflammatory Bowel Diseases ; RNA, Messenger ; SARS-CoV-2 ; Thrombin
    Chemical Substances Antibodies, Viral ; BNT162 Vaccine ; Immunoglobulin G ; Immunoglobulin M ; RNA, Messenger ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2023-10-30
    Publishing country Switzerland
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1257072
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis.

    Kacsándi, Dorottya / Fagyas, Miklós / Horváth, Ágnes / Végh, Edit / Pusztai, Anita / Czókolyová, Monika / Soós, Boglárka / Szabó, Attila Ádám / Hamar, Attila / Pethő, Zsófia / Bodnár, Nóra / Kerekes, György / Hodosi, Katalin / Szamosi, Szilvia / Szűcs, Gabriella / Papp, Zoltán / Szekanecz, Zoltán

    Frontiers in medicine

    2023  Volume 10, Page(s) 1226760

    Abstract: Introduction: The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) ... ...

    Abstract Introduction: The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers.
    Patients and methods: Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment.
    Results: After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (
    Conclusion: JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.
    Language English
    Publishing date 2023-10-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1226760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The majority of severe COVID-19 patients develop anti-cardiac autoantibodies.

    Fagyas, Miklós / Nagy, Béla / Ráduly, Arnold Péter / Mányiné, Ivetta Siket / Mártha, Lilla / Erdősi, Gábor / Sipka, Sándor / Enyedi, Enikő / Szabó, Attila Ádám / Pólik, Zsófia / Kappelmayer, János / Papp, Zoltán / Borbély, Attila / Szabó, Tamás / Balla, József / Balla, György / Bai, Péter / Bácsi, Attila / Tóth, Attila

    GeroScience

    2022  

    Abstract: Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to ... ...

    Abstract Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment. Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).
    Language English
    Publishing date 2022-09-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-022-00649-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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