Browsing by Author "Jeremic, Ivica (36016708800)"

Baseline sympathetic activity was found to be elevated in rheumatoid arthritis (RA) patients and it is related to increased cardiovascular risk in these patients. Although many studies have highlighted the association between RA and increased cardiac sympathetic activity, the underlying mechanistic links remain unclear. The aim of the present study was to understand how diseases-triggered changes in gene expression may result in maladaptive physiological changes. Our results suggest that the equilibrium between noradrenaline synthesis, release and reuptake was disrupted in the ventricles of arthritic rats. In the acute phase of the arthritic process, decreased gene expression of MAO-A might lead to accumulation of noradrenaline in myocardial interstitial space, whereas increased gene expression of NET protected cardiomyocytes from the deleterious effects of enhanced noradrenaline. During the chronic phase, reduced expression of β1-adrenoceptor and decreased efficiency of noradrenaline reuptake contribute to progressive damage of the myocardium and limits heart efficiency. © 2017 Elsevier B.V.

Baseline sympathetic activity was found to be elevated in rheumatoid arthritis (RA) patients and it is related to increased cardiovascular risk in these patients. Although many studies have highlighted the association between RA and increased cardiac sympathetic activity, the underlying mechanistic links remain unclear. The aim of the present study was to understand how diseases-triggered changes in gene expression may result in maladaptive physiological changes. Our results suggest that the equilibrium between noradrenaline synthesis, release and reuptake was disrupted in the ventricles of arthritic rats. In the acute phase of the arthritic process, decreased gene expression of MAO-A might lead to accumulation of noradrenaline in myocardial interstitial space, whereas increased gene expression of NET protected cardiomyocytes from the deleterious effects of enhanced noradrenaline. During the chronic phase, reduced expression of β1-adrenoceptor and decreased efficiency of noradrenaline reuptake contribute to progressive damage of the myocardium and limits heart efficiency. © 2017 Elsevier B.V.

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and n-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and n-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 μg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and n-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and n-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 μg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity. © Georg Thieme Verlag KG Stuttgart · New York.

Objective: Cross-cultural validation of the Serbian version of the Modified Falls Efficacy Scale (MFES). Methods: This cross-sectional study involved 257 women aged 65 years and above who were referred for dual-energy x-ray absorptiometry examination at the Railway Healthcare Institute in Belgrade, Serbia, between January and April 2016. Data collection comprised of a sociodemographic questionnaire and Geriatric Depression Scale-Short Form (GDS-SF) questionnaire, and data related to fractures, level of physical activity, use of medications that can increase the risk of falls, and frequency of falls in the past 12 months. None of the study participants had been previously treated for osteoporosis. The internal consistency of the questionnaire items was assessed via Cronbach's alpha, whereas the interclass correlation coefficient (ICC) was used to calculate test-retest reliability based on the sample of 257 women. We also evaluated concurrent, convergent, and construct validity. Results: Cronbach's alpha for the total assay score was 0.98. Correlations among the items ranged from 0.84 to 0.93. While ICC for the scale as a whole was 0.99 (95% confidence interval 0.98-0.99), ICC pertaining to individual items ranged from 0.82 to 0.99. Concurrent validity analysis revealed a significant positive correlation between MFES scores and the reported level of physical activity (ρ = 0.34; P < 0.01). Convergent validity was tested through the ratio of MFES and sociodemographic variables. The findings indicated presence of a significant negative correlation between the MFES scores and age (ρ = -0.32; P < 0.01), age of menopause onset (ρ = -0.16; P = 0.01), and GDS-SF scores (ρ = -0.12; P = 0.04), and positive correlation between MFES and the level of social activity (ρ = 0.22; P < 0.01). Significant differences were noted between the MFES scores of participants who had no history fractures and those who did (U = 5277.50; P < 0.01), and between scores of women who reported falling in the past 12 months and those who did not (U = 4968.50; P < 0.01). Similarly, significant differences (P < 0.01) in the scores pertaining to each MFES item were observed between women who had experienced falls in the past (n = 101) and those who had not (n = 156). Conclusion: The Serbian version of the MFES is a reliable and valid instrument that can be used in both clinical practice and research to describe and measure self-perceived fear of falling in older individuals. © 2017 by The North American Menopause Society.

Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells. © Georg Thieme Verlag KG Stuttgart.

Menopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells. © Georg Thieme Verlag KG Stuttgart.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus. Copyright © 2023 Banko, Cirkovic, Miskovic, Jeremic, Grk, Basaric, Lazarevic, Raskovic, Despotovic and Miljanovic.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus. Copyright © 2023 Banko, Cirkovic, Miskovic, Jeremic, Grk, Basaric, Lazarevic, Raskovic, Despotovic and Miljanovic.

We assessed the relationship between the serum levels of antibodies against double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement components with one another, with organ involvement and overall disease activity in patients with systemic lupus erythematosus (SLE). One hundred seventy-five sera from 99 patients with SLE, 31 sera of patients with other connective tissue diseases, and 20 sera from healthy blood donors were tested. SLE disease activity was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most significant risk factor for renal involvement were anti-C1q antibodies (OR = 3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99, p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05), and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR = 3.32, p < 0.01). Multiple linear regression analysis showed that disease activity in SLE could be predicted by the levels of antibodies against dsDNA determined by standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti-dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K. Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5) (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies represented a risk for renal, joint, and most importantly for serosal involvement. Our results suggest that simple and reliable ELISA for high-avidity anti-dsDNA antibodies is the test of good clinical utility for the assessment of global SLE activity. © 2013 Clinical Rheumatology.

Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naïve SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p < 0.001), BAFF and DNase I concentration (p < 0.01). Contrary, NETolytic activity was lower in SLE patients (p < 0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p < 0.001, p < 0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p < 0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p < 0.01), cfDNA and BAFF levels (p < 0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p < 0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naïve SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background : Decreased activity of serum desoxyribonuclease I (DNase I) in systemic lupus erythematosus (SLE) has been reported, but its role as a biomarker in SLE is still unelucidated. Methods : Seventy-seven SLE patients (aged 39.6 ± 13.1 years) were studied for serum DNase I activity, levels of antinuclear (ANA), anti-dsDNA [high-avidity ELISA, conventional ELISA and indirect immunofluorescence (IIF)], anti-nucleosome, anti-histone antibodies, complement components C3 and C4. SLE disease activity was evaluated by disease activity index (SLEDAI-2K). Thirty-five patients were serologically and clinically followed for 3 - 12 months (mean 5.6 ± 2.8). Thirty-seven healthy blood donors were the control group. Results : DNase I activity in SLE patients was lower than in healthy controls (p < 0.01). DNase I activity was in positive correlation with SLEDAI-2K (p < 0.01), levels of ANA, anti-dsDNA, anti-nucleosome and anti-histone antibodies (p < 0.01) and in negative correlation with C3 concentration (p < 0.05). The highest correlation was found between DNase I activity and anti-dsDNA concentrations determined by high-avidity ELISA (r = 0.624), followed by IIF (r = 0.541) and conventional ELISA (r = 0.405). In the follow-up study, DNase I activity also correlated with SLEDAI-2K (p < 0.01). SLE patients with low DNase I activity more frequently had SLE-specific cutaneous lesions (p < 0.05). Conclusions : Monitoring of DNase I activity simultaneously with SLEDAI-2K might be a useful tool in the followup of SLE. An increase of DNase I activity characterized relapse in most SLE patients, although it did not reach the levels of healthy individuals. A decrease of DNase I activity in SLE flare-ups might be a functional biomarker of a subset of patients with specific dysfunction of apoptotic chromatin degradation.

Background : Decreased activity of serum desoxyribonuclease I (DNase I) in systemic lupus erythematosus (SLE) has been reported, but its role as a biomarker in SLE is still unelucidated. Methods : Seventy-seven SLE patients (aged 39.6 ± 13.1 years) were studied for serum DNase I activity, levels of antinuclear (ANA), anti-dsDNA [high-avidity ELISA, conventional ELISA and indirect immunofluorescence (IIF)], anti-nucleosome, anti-histone antibodies, complement components C3 and C4. SLE disease activity was evaluated by disease activity index (SLEDAI-2K). Thirty-five patients were serologically and clinically followed for 3 - 12 months (mean 5.6 ± 2.8). Thirty-seven healthy blood donors were the control group. Results : DNase I activity in SLE patients was lower than in healthy controls (p < 0.01). DNase I activity was in positive correlation with SLEDAI-2K (p < 0.01), levels of ANA, anti-dsDNA, anti-nucleosome and anti-histone antibodies (p < 0.01) and in negative correlation with C3 concentration (p < 0.05). The highest correlation was found between DNase I activity and anti-dsDNA concentrations determined by high-avidity ELISA (r = 0.624), followed by IIF (r = 0.541) and conventional ELISA (r = 0.405). In the follow-up study, DNase I activity also correlated with SLEDAI-2K (p < 0.01). SLE patients with low DNase I activity more frequently had SLE-specific cutaneous lesions (p < 0.05). Conclusions : Monitoring of DNase I activity simultaneously with SLEDAI-2K might be a useful tool in the followup of SLE. An increase of DNase I activity characterized relapse in most SLE patients, although it did not reach the levels of healthy individuals. A decrease of DNase I activity in SLE flare-ups might be a functional biomarker of a subset of patients with specific dysfunction of apoptotic chromatin degradation.

Introduction: After the Serbian community hospitals had reached their full capacity during the pandemic, new institutions were enrolled into the coronavirus disease 2019 (COVID-19) system as temporary COVID hospitals (TCH). These hospitals usually had no intensive care units (ICU) and no possibility to treat severely ill patients. The aim of this study was to identify risk factors at the time of triage that could help identify patients that will require ICU treatment and cannot be treated in a TCH. Methodology: In this retrospective study, a total of 158 patients with COVID-19 infection were enrolled. The demographic information, underlying comorbidities, laboratory findings, chest X-rays, computed tomography scans, and clinical outcomes were obtained from medical records. Deterioration of a patient’s condition was regarded as a need for further transfer to ICU. Results: During the hospitalization 15.2% of patients required transfer to ICU. Patients with deterioration were significantly older and there was no difference between genders. We observed a higher prevalence of hypertension, other cardiovascular diseases, lower lymphocyte and platelet counts, and higher IL-6 and troponin T in patients with deterioration. The multivariate logistical regression model showed that only age was an independent risk factor for deterioration and with each year of age, the risk for poor outcome increased by 8%. Conclusions: Patients with cardiovascular risk factors, low lymphocyte and platelet counts, high IL-6 and troponin T and, especially, increased age should not be treated in a TCH because of the high possibility for deterioration and need for transfer to an ICU. Copyright © 2023 Djurdjevic et al.

Introduction: After the Serbian community hospitals had reached their full capacity during the pandemic, new institutions were enrolled into the coronavirus disease 2019 (COVID-19) system as temporary COVID hospitals (TCH). These hospitals usually had no intensive care units (ICU) and no possibility to treat severely ill patients. The aim of this study was to identify risk factors at the time of triage that could help identify patients that will require ICU treatment and cannot be treated in a TCH. Methodology: In this retrospective study, a total of 158 patients with COVID-19 infection were enrolled. The demographic information, underlying comorbidities, laboratory findings, chest X-rays, computed tomography scans, and clinical outcomes were obtained from medical records. Deterioration of a patient’s condition was regarded as a need for further transfer to ICU. Results: During the hospitalization 15.2% of patients required transfer to ICU. Patients with deterioration were significantly older and there was no difference between genders. We observed a higher prevalence of hypertension, other cardiovascular diseases, lower lymphocyte and platelet counts, and higher IL-6 and troponin T in patients with deterioration. The multivariate logistical regression model showed that only age was an independent risk factor for deterioration and with each year of age, the risk for poor outcome increased by 8%. Conclusions: Patients with cardiovascular risk factors, low lymphocyte and platelet counts, high IL-6 and troponin T and, especially, increased age should not be treated in a TCH because of the high possibility for deterioration and need for transfer to an ICU. Copyright © 2023 Djurdjevic et al.

Sideritis scardica (mountain tea) is an endemic plant on the Balkan Peninsula traditionally used for treating different conditions, mainly of inflammatory nature. This study was aimed to examine the cytotoxic activity of different S. scardica extracts against the rat glioma C6 line and rat astrocytes in primary culture. The obtained data revealed that diethyl ether (extract 2) and ethyl acetate (extract 3) extracts of S. scardica exerted a cytotoxic effect on C6 rat glioma cells. Diethyl ether extract induced an increase in reactive oxygen species production, leading to apoptotic and autophagic cell death. Ethyl acetate extract induced G2 M cell cycle arrest and autophagy. None of the tested extracts was cytotoxic to rat astrocytes in primary culture. Cytotoxic effects of S. scardica extracts were, at least in part, mediated by their flavonoid constituents apigenin and luteolin that, when applied alone, induced cell cycle arrest, apoptosis, and autophagy. © Georg Thieme Verlag KG Stuttgart New York.

Sideritis scardica (mountain tea) is an endemic plant on the Balkan Peninsula traditionally used for treating different conditions, mainly of inflammatory nature. This study was aimed to examine the cytotoxic activity of different S. scardica extracts against the rat glioma C6 line and rat astrocytes in primary culture. The obtained data revealed that diethyl ether (extract 2) and ethyl acetate (extract 3) extracts of S. scardica exerted a cytotoxic effect on C6 rat glioma cells. Diethyl ether extract induced an increase in reactive oxygen species production, leading to apoptotic and autophagic cell death. Ethyl acetate extract induced G2 M cell cycle arrest and autophagy. None of the tested extracts was cytotoxic to rat astrocytes in primary culture. Cytotoxic effects of S. scardica extracts were, at least in part, mediated by their flavonoid constituents apigenin and luteolin that, when applied alone, induced cell cycle arrest, apoptosis, and autophagy. © Georg Thieme Verlag KG Stuttgart New York.