Publications by authors named "Tamara Kovacevic"

7 Publications

  • Page 1 of 1

Predictive value of admission glycemia in diabetics with pulmonary embolism compared to non-diabetic patients.

Acta Diabetol 2022 May 30;59(5):653-659. Epub 2022 Jan 30.

Clinic of Cardiology and Emergency Internal Medicine, Military Medical Academy, School of Medicine, University of Defense, Belgrade, Serbia.

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2.

Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5-10.0 mmol/L; III: 10.0-15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5-6.3 mmol/L; III: 6.3-7.9 mmol/L; IV: > 7.9 mmol/L).

Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017-6.027) only in DM patients.

Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality.
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May 2022

Monoclonal antibody 26 cross-reactive with β2-glycoprotein I affects human trophoblast invasion in vitro.

Eur J Obstet Gynecol Reprod Biol 2013 Nov 16;171(1):23-9. Epub 2013 Aug 16.

Institute for the Application of Nuclear Energy - INEP, University of Belgrade, Serbia.

Objective: Monoclonal antibody 26 (MAb 26) raised against tetanus toxoid has documented cross-reactivity with β2-glycoprotein I. Passive introduction of this antibody in mice results in an antiphospholipid syndrome-like condition. We investigated the effects of MAb 26 on first trimester human trophoblast in vitro.

Study Design: Binding of MAb 26 to placental tissue trophoblast, isolated cytotrophoblast and HTR-8/SVneo cells was analyzed by immunohisto(cyto)chemistry. Possible effects on cell invasion in vitro were assessed by Matrigel assay. Effects on cell viability were assessed by MTT test. A possibility that MAb 26 induces change in levels of effector molecules important for cell invasion was investigated. Integrin subunits α1, α5 and β1, and galectin-1, were analyzed by qPCR and Western blot. Metalloproteinases -2 and -9 were assessed by gelatin zymography.

Results: Immunohisto(cyto)chemistry showed binding of MAb 26 to placental tissue trophoblast, isolated cytotrophoblast and HTR-8/SVneo cells. The antibody had a significant inhibitory effect on cell invasion by both isolated cytotrophoblast and HTR-8/SVneo. The antibody induced significant decrease in protein levels of metalloproteinases, integrin subunit α1 and galectin-1. Cell viability was not affected.

Conclusion: MAb 26 reduces trophoblast invasion in vitro through decreased levels of metalloproteinases-2 and -9, integrin α1 and galectin-1.
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November 2013

Galectin-1 is part of human trophoblast invasion machinery--a functional study in vitro.

PLoS One 2011 8;6(12):e28514. Epub 2011 Dec 8.

Laboratory for Biology of Reproduction, Institute INEP, University of Belgrade, Belgrade, Serbia.

Background: Interactions of glycoconjugates with endogenous galectins, have been long proposed to participate in several reproductive processes including implantation. In human placenta gal-1, gal-3, gal-8, and gal-13 proteins are known to be present. Each of them has been proposed to play multiple functions, but so far no clear picture has emerged. We hypothesized that gal-1 participates in trophoblast invasion, and conducted Matrigel invasion assay using isolated cytotrophoblast from first trimester placenta and HTR-8/SVneo cell line to test it.

Methods And Findings: Function blocking anti-gal-1 antibody was employed to assess participation of endogenous gal-1 in cell adhesion, cell invasion of HTR-8/SVneo cells. When gal-1 was blocked in isolated trophoblast cell invasion was reduced to 75% of control (SEM ± 6.3, P<0.001) and to 66% of control (SEM ± 1.7, P<0.001) in HTR-8/SVneo cell line. Increased availability of gal-1, as two molecular forms of recombinant human gal-1 (CS-gal-1 and Ox-gal-1), resulted in increased cell invasion by cytotrophoblast to 151% (SEM ± 16, P<0.01) with 1 ng/ml of CS-gal-1, and to 192% (SEM ± 51, P<0.05) with 1 µg/ml of Ox-gal-1. Stimulation was also observed in HTR-8/SVneo cells, to 317% (SEM ± 58, P<0.001) by CS-gal-1, and to 200% (SEM ± 24, P<0.001) by Ox-gal-1 at 1 µg/ml. Both sets of results confirmed involvement of gal-1 in trophoblast invasion. Galectin profile of isolated cytotrophoblast and HTR-8/SVneo cells was established using RT-PCR and real-time PCR and found to consist of gal-1, gal-3 and gal-8 for both cell types. Only gal-1 was located at the trophoblast cell membrane, as determined by FACS analysis, which is consistent with the results of the functional tests.

Conclusion And Significance: These findings qualify gal-1 as a member of human trophoblast cell invasion machinery.
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April 2012

Effects of anti-phospholipid antibodies on a human trophoblast cell line (HTR-8/SVneo).

Acta Histochem 2010 2;112(1):34-41. Epub 2008 Oct 2.

Institute for Application of Nuclear Energy - INEP, University of Belgrade, Serbia.

Antibodies to phospholipids (aPL) have been shown to adversely affect trophoblast invasion in vivo and in vitro. HTR-8/SVneo cells derived from first trimester of pregnancy extravillous trophoblast were studied. Matrigel invasion assay, cytochemistry and cell-based enzyme-linked immunosorbant assay (ELISA) with aPL or normal IgG was used. Our data show that aPL at 100 microg/ml decrease invasiveness of HTR-8/SVneo cells to 60% of control (p<0.01), and this was also shown for primary cytotrophoblast (to 15.5% of control, p<0.001). aPL treatment caused a significant decrease in integrin alpha(1), alpha(5), and beta(1) proteins (86%, 84%, and 87%, respectively). We conclude that HTR-8/SVneo cell culture is a suitable model to study mechanisms of action of aPL on trophoblast, which in HTR-8/SVneo cells inhibit invasion by decreasing integrins alpha(5), alpha(1), and beta(1).
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March 2010

High-dose atorvastatin in peripheral arterial disease (PAD): effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial.

Thromb Haemost 2008 Jan;99(1):182-9

Clinic of Angiology, Department of Medicine, University Hospital Zurich, Switzerland.

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months.
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January 2008

Blood fluidity and outcome after femoropopliteal percutaneous transluminal angioplasty (PTA): role of plasma viscosity and low platelet count in predicting restenosis.

Clin Hemorheol Microcirc 2005 ;32(2):159-68

Division of Angiology, Department of Medicine, University Hospital Zurich, Switzerland.

Rheological abnormalities are well known in patients with peripheral arterial occlusive disease (PAOD). We wanted to determine whether rheological variables are related to restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). In 114 patients (62 men; median age 70 years) undergoing femoropopliteal PTA for symptomatic peripheral arterial occlusive disease (PAOD) plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, fibrinogen, platelet count, leukocytes and C-reactive protein were determined the day after the procedure and at 1, 3, and 12 months. The primary endpoint was restenosis >50% documented by duplexsonography up to 12 months. Cox proportional hazards analysis was used to assess the risk of restenosis for postinterventional values of rheological variables. Forty-eight patients (42%) developed restenosis at 12 months. Patients with restenosis had higher baseline plasma viscosity (PV) (medians, 1.71 vs. 1.65 millipascal seconds [mPa.s]; p = 0.04) and lower platelet count (224 vs. 240 x 10(3)/microl; p = 0.03) than patients without restenosis. The hazard ratio (HR; 95% CI) of incident restenosis was 9.2 (1.12-76; p = 0.03) for PV and 0.99 (0.99-1.0; p = 0.07) for PLT. When examining jointly both high PV and low platelet count (PLT), patients with PV > 1.66 mPa.s and PLT < 233 x 10(3)/microl (i.e. variables split at their respective median) had an increased risk of restenosis (log-rank test p = 0.01). Multivariate Cox proportional hazard analysis showed that plasma viscosity (p = 0.02), low platelet count (p = 0.01), lesion length (p = 0.0037) and lack of hypertension (p = 0.01) were associated with restenosis at 12 months. No associations were found between restenosis and the other rheological and inflammatory variables studied. Our data suggest that increased PV and low PLT contribute to restenosis after femoropopliteal PTA.
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July 2005

Plasma homocysteine and restenosis after femoropopliteal angioplasty.

J Endovasc Ther 2004 Jun;11(3):302-9

Department of Medicine, University Hospital Zurich, Switzerland.

Purpose: To assess the relationship between plasma homocysteine levels and restenosis after femoropopliteal percutaneous transluminal angioplasty.

Methods: Over a 10-month period, 128 consecutive, symptomatic patients (72 men; median age 70 years) having successful femoropopliteal angioplasty for atherosclerotic occlusive disease were prospectively enrolled in the study. Plasma homocysteine levels were determined the day before the procedure. The primary endpoint was restenosis >50%, documented by duplex sonography, at up to 12 months' follow-up. Cox proportional hazards analysis was used to determine the risk of restenosis in relation to pretreatment homocysteine levels.

Results: The restenosis rate at 12 months was 46%. Median baseline plasma homocysteine levels were not different in patients with and without restenosis (15.4 versus 16.7 micromol/L, p=0.30). Compared to patients with homocysteine levels /=19.7 micromol/L (upper tertile, n=42) (p=0.38). Multivariate analysis showed that lesion length (p<0.0001) and lack of hypertension (p=0.0013) were associated with restenosis.

Conclusions: Elevated plasma homocysteine levels are not associated with restenosis after femoropopliteal angioplasty. Therefore, plasma homocysteine cannot be considered as an important risk factor influencing the outcome after initially successful angioplasty in femoropopliteal arteries.
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June 2004