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Open access

Emőke Horváth, Adina Huțanu, Alex Orădan, Liviu Chiriac, Daniela Lucia Muntean, Előd-Ernő Nagy and Minodora Dobreanu

Abstract

Introduction: Experimental acute cerebral ischemia quickly triggers circulating inflammatory cells, provoking infiltration of neutrophils and macrophages in the damaged brain region. N-3 polyunsaturated fatty acids alleviate the ischemic deterioration, however, their potential effect on bone marrow cell mobilization is less known.

Materials and methods: healthy male Wistar rats were submitted to intraperitoneal saline injection (n=10, sham Group), transient middle cerebral artery occlusion (tMCAO) and saline injection (n=10, placebo Group), tMCAO and highly purified fish-oil administration (n=10, T Group). At the two latter groups, twenty-four hours after tMCAO, MRI scans were performed to identify the ischemic regions; the eligible animals were sacrificed, the left parietal bones being removed and subjected to qualitative and quantitative histological and immunohistochemical analysis.

Results: The active hematopoietic surface was maximal at the T-Group, being significantly lower in the P- and S-Groups (p=0.006 and p= 0.017). The MPO positive surface increased significantly in the T-compared to the S-Group (22.57± 0.86 % vs. 18.87± 0.68%, p= 0.004). Arg1 expression was significantly higher (p=0.001), while iNOS expression was lower (p=0.004) in the T- than in the P-Group, but similar to the S-group. The Arg1/iNOS2 ratio was higher in the FO-treated than in the P-group (p<0.001).

Conclusion: the ischemic conditions triggered granulopoiesis and the increase of iNOS2 positive, type M1 macrophage in the rat bone marrow. Fish-oil treatment generated the expansion of overall hematopoietic surface along with normalization of iNOS2, up-regulating the potentially protective Arg1 positive M2 type macrophages and causing a significant shift in the M2/M1 ratio.

Open access

Brîndușa Țilea, Septimiu Voidăzan, Rodica Bălașa, Adina Huțanu and Andrea Fodor

Abstract

Background: During the acute inflammatory process, the CXCL13 chemokine plays an important role in B cell recruitment within the central nervous system (CNS).

Objective: The objective of the study consisted of the evaluation of CXCL13 chemokine cerebral spinal fluid (CSF) and plasma levels in patients with acute infectious and non-infectious neurological diseases correlated with pleocytosis and CSF protein levels.

Material and method: This retrospective study was conducted over one year and included 72 patients. Thirty-eight patients (52.8%) suffering from infectious neurological disease, acute viral and bacterial meningitis, meningoencephalitis, and 34 patients (44.2%) diagnosed with non-infectious neurological diseases.

CXCL13 chemokine CSF and plasma levels were determined through the ELISA technique with the Human CXCL13/BLC/BCA-1 kit. CSF cell count, glucose and protein levels, along with anti-Borrelia burgdorferi antibodies were monitored using the ELISA technique.

Results: CXCL13 chemokine levels in the CSF of patients with acute infectious neurological diseases showed a median value of 23.07 pg/mL, which was significantly higher in comparison with the median value of 11.5 pg/mL of patients with noninfectious neurological diseases (p-0.03). CXCL13 median plasma concentration in patients with infectious neurological diseases was 108.1 pg/mL, in comparison with the second patient category, 50.7 pg/ml (p-0.001). We observed a statistically significant association between CXCL13 concentrations, CSF cell count and proteins. The higher the CXCL13 chemokine level, the more increased the cell count was.

Conclusions: CXCL13 levels in the CSF was significantly increased in patients with acute infectious neurological diseases compared with patients with non-infectious diseases. Moreover, CXCL13 chemokine concentration was significantly correlated with the number of cells and proteins in the CSF of patients suffering from neuroinfections.

Open access

Ioan Ţilea, Andreea Varga, Septimiu Voidăzan and Adina Huţanu

Abstract

Background: Twenty-four hours dynamic blood pressure (BP) behaviour displays dipper profile defined as nocturnal systolic BP (SBP) reduction>10% compared to daytime. Non-dipper profile, nocturnal absence of SBP fall, associates an increased cardiovascular risk. We investigated the concomitant association of inflammatory bio-markers - high-sensitivity- C-reactive protein (hs-CRP), Human Chitinase3-like1 (YKL-40) and autonomic nervous system (total brain-derived neurotrophic factor, BDNF) with respect to non-dipping blood pressure status.

Material and method: Using 24h automatic BP measurements, 80 known hypertensive patients were divided into two groups: dipper group included fifty-one dipper patients (age 55.6 ±13.5 years) and non-dipper group consisted of 29 non-dipper subjects (62.07±12.03 years). Serum levels of hs-CRP were evaluated with enhanced immunoturbidimetric assay. Plasma levels of YKL-40 were measured by commercial sandwich ELISA using microplate coated with a monoclonal antibody for CHI3L1. Plasma levels of total BDNF were determined using quantitative sandwich enzyme-linked immunoassay. Statistical analysis of obtained data was performed.

Results: In the non-dipper group, a significant positive association with age over 60 years, hs-CRP values above 1.90 mg/dl was observed along with increased mean values of YKL-40. Non-dipper status is independently and statistically significantly associated with elevated levels of hs-CRP (OR: 3.248, 95% CI: 1.022-10.317, p=0.046) in multivariate odds ratio analysis. No statistically significant positive association between a median total BDNF plasma level of 1430 pg/ml and the non-dipper hypertension profile was identified.

Conclusion: Our study demonstrated that patients over 60 years, in particular, have a higher probability to present a non-dipping pattern of hypertension. hs-CRP and YKL-40 values are more likely to increase in the non-dipping hypertensive patients, and hs-CRP values above 1.9 mg/dl can identify the presence of a non-dipper blood pressure profile.

Open access

Simona Cernea, Adina Huţanu, Ligia Coroş and Minodora Dobreanu

Abstract

Objectives: The primary aim of this study was to assess residual beta cell function at diagnosis of type 2 diabetes and identify accessible laboratory markers that best estimate it. The secondary objective was to evaluate the change in beta cell function 6 months after starting different therapeutical regimens. Materials and methods: Forty seven subjects were included in the study and each performed a 75-g oral glucose tolerance test (OGTT) at baseline and after 6 months. Metabolic and immunologic parameters were determined from fasting samples. According to the degree of metabolic decompensation, specific therapy was started: metformin, metformin plus gliclazide or insulin therapy (with/out metformin). Early and total beta cell function was evaluated by the disposition index (DI) calculated for 30 minutes and 120 minutes, respectively. Results: At diagnosis, fasting blood glucose (BG) and HbA1c varied largely (129-521 mg/dl and 5.5-14%, respectively). The DI30 and DI120 decreased with more severe glycemic decompensation. For both DI30 and DI120 significant negative correlations were found for glycemic markers (HbA1c, 2-hour BG and maximal BG amplitude) and positive correlation for 2- hour C peptide (p<0.0001 for all). HbA1c value of 7% discriminated an important decrease of DI30 and DI120. Insulin and combined therapy significantly improved DI120 at 6 months (p: 0.0062 and 0.01, respectively), while DI30 was improved only with insulin therapy (p: 0.0326). Conclusions: Beta cell function at onset correlated with HbA1c, 2-hour BG and C peptide during OGTT. Thus OGTT and HbA1c are pivotal for evaluation of beta cell function. Insulin therapy improved early and total insulin secretion at 6 months.

Open access

Simona Cernea, Floredana-Laura Şular, Adina Huţanu and Septimiu Voidăzan

Abstract

Background. The study aimed to evaluate the correlations of cognitive function with metabolic, nutritional, hormonal and immunologic parameters in patients with type 2 diabetes (T2D), in order to identify markers of cognitive impairment.

Material and methods. This cross-sectional study included 216 T2D patients and 23 healthy individuals (HC). The cognitive status was evaluated by the MoCA test. From HC and 145 T2D patients several parameters were also determined: C-peptide, vitamin B12, high-sensitivity CRP (by chemiluminescent immunometric assay), HbA1c, lipids, cortisol, TSH, Mg (by a Cobas 6000 analyzer), glucose (by glucose-oxidase method) and leptin and adiponectin (by ELISA method). Statistical significance was set at p < 0.05.

Results. There was a significant difference in the MoCA scores between HC and T2D groups (26.0(17.0-29.0) vs. 23.0(13.0- 31.0) points; p: 0.004). T2D patients with cognitive dysfunction were significantly older and less formally educated (p < 0.0001). Age negatively correlated with MoCA scores (-0.31; 95%CI:-0.42,-0.18; p < 0.0001). T2D patients had significantly lower visuospatial/executive (4.0(0.0-5.0) vs. 5.0(2.0-5.0) points; p: 0.04) and delayed recall scores (2.0(0.0- 5.0) vs. 3.0(1.0-5.0) points; p: 0.03) and lower serum Mg concentrations (0.81(0.12-0.99) vs. 0.92(0.41-1.35) mmol/l, p < 0.0001). Serum Mg levels positively correlated with MoCA scores (0.24, 95%CI: 0.07, 0.39; p: 0.003) and with visuospatial/ executive (0.30; 95%CI: 0.14, 0.45; p: 0.0002) and naming functions (0.18; 95%CI: 0.01, 0.34; p: 0.02).

Conclusions. Patients with T2D had significant cognitive impairment, with decrements in the visuospatial/executive and delayed recall domains. Younger age and higher education correlated with better cognitive function. Serum Mg levels correlated positively with overall cognitive function and with visuospatial/executive and naming domains.

Open access

Septimiu Voidazan, Horatiu Moldovan, Adina Huţanu, Doina Giurgiu, Stelian Morariu, Lode Godderis and Radu-Corneliu Duca

Abstract

Purpose: Our study focuses on elucidating if two common inflammatory biomarkers, easily performed in any laboratory - high-sensitivity C-reactive protein (hsCRP), as well as fibrinogen - could be used to assess the personal health risk of workers exposed to a complex occupational exposure to ultrafine particles (UFP) and a mixture of organic solvents. Methods: To assess the inflammatory response on the body, laboratory determinations were performed by testing the serum levels of hsCRP and fibrinogen, in exposed and unexposed groups. Results: There are no statistically significant differences for hsCRPs (p-0.25), medians were similar in groups. The mean values of fibrinogen in the three groups were: in the workers group (1st group): 346.2 mg/dl, in the office staff group (2nd group): 328.7 mg/dl, and in the control group (3rd group): 284.8 mg/dl, with significant differences between 1st group vs 3rd group and between 2nd group vs 3rd group (p-0.002). UFP levels differ between the groups, as follows: 1st group were exposed to the highest levels, ranging from 48349 to 3404000 part/cm3; 2nd group, ranging from 17371 to 40595 part/cm3; and 3rd group, ranging from 213 to 16255 part/cm3. Conclusions: Our study demonstrates that fibrinogen is a useful inflammatory biomarker for exposure to a mixture of UFP and organic solvents. On the other hand, hsCRP is not a useful inflammatory biomarker in occupational exposure to UFP and organic solvents. Further studies are needed to demonstrate the extent to which fibrinogen is more or less influenced by organic solvents or UFP alone.

Open access

Anca-Meda Georgescu, Janos Szederjesi, Septimiu Voidăzan, Minodora Dobreanu, Sanda Maria Copotoiu, Adina Huțanu and Leonard Azamfirei

Abstract

Background. Validating new sepsis biomarkers can contribute to early diagnosis and initiation of therapy. The aim of this study is to evaluate the sepsis predictive capacity of soluble urokinase plasminogen receptor (suPAR) and its role in evaluating the prognosis of bloodstream infections. Material and method. We conducted a prospective pilot study on 49 systemic inflammatory response syndrome (SIRS) patients admitted to the intensive care unit (ICU), that were divided, on the basis of bacteremia in group A (SIRS with bacteremia, n=14) and group B (SIRS without bacteremia, n=35). Hemoculture and blood samples were drawn on the first day to determine suPAR, C-reactive protein (CRP) and procalcitonin (PCT). We set to identify significant cut-off values in estimating bacteremia and mortality in septic patients. Results. In group A, suPAR values were 14.3 ng/mL (range 10-45.5 ng/mL) and in group B, 9.85 ng/mL (range 3.4-48 ng/mL) p=0.008. Area under the curve (AUC) for suPAR was 0.745 (95% CI: 0.600-0.859), for CRP 0.613 (95% CI: 0.522-0.799) and for PCT 0.718 (95% CI: 0.477-0.769). Cut-off value for suPAR in bacteremia prediction was 9.885 ng/mL, with 100% sensibility and 51.43% specificity. Mortality in group A was 85.7% (12/14) and in group B 74.3% (26/39), p>0.05. Area under the curve (AUC) for suPAR was 0.750 (95% CI: 0.455-0.936), for CRP 0.613 (95% CI: 0.413-0.913) and for PCT 0.618 (95% CI: 0.373-0.888). Cut-off value of suPAR in predicting mortality was 11.5 ng/mL, with 66.67% sensibility and 100% specificity. Conclusions. In our study suPAR had a predictive capacity for bacteremia and seems to be an independent factor for mortality prognosis in septic patients.

Open access

Adina Huțanu, Smaranda Maier, Rodica Bălaşa, Oana Roxana Oprea, Ştefan Barbu, Septimiu Voidăzan and Minodora Dobreanu

Abstract

Background: The aim of the study was to determine the utility of plasma NfH in correlation with serum hsCRP for severity and short-term functional outcome prediction after ischemic stroke. Methods: 124 patients and 40 healthy controls were enrolled, serial plasma neurofilament heavy chains and hsCRP concentrations were measured and evaluated for TOAST subtype, stroke severity and functional outcome at discharge. Results: Serum level of hsCRP was significantly higher in patients versus controls (p<0.05) with no difference between TOAST subtypes. Plasma NfH concentration on day 5 was higher in CE stroke compared to LAA group and SVO group. A positive correlation between NfH levels on day 5 and mRS at discharge (r=0.304, p=0.001) and a gender stratification of hsCRP and mRS at discharge was found. Values of 6.04 mg/l for hsCRP and 46.4 ng/ml for NfH were found predictive for unfavorable short-term outcome, but after adjusting for age, sex and stroke severity, the prediction power was lost. Conclusions: Plasma concentration of NfH shows a significant increase over the first five days after ischemic stroke, in correlation with inflammatory status and short-term evolution.

Open access

János Szederjesi, Anca Georgescu, Ario Santini, Emőke Almásy, Alexandra Lazar, Adina Hutanu, Sanda-Maria Copotoiu and Leonard Azamfirei

Abstract

Sepsis represents one the main cause of death in patients admitted to the intensive care. Biomarkers offer an alternative approach to the diagnostic and prognostic evaluation and improve the outcomes. Angiopoietin 2 (Ang-2) and Tyrosine kinase 2 (Tie-2) are biomarkers which may be involved in sepsis, Ang-2 being responsible for vascular remodelling while Tie-2 is their endothelial receptor.

The aim of the study: To assess the Ang-2, Tie-2 and Ang-2/Tie-2 ratio serum levels in septic and non-septic patients and to investigate the independent value of circulating Ang-2, Tie-2, and Ang-2/Tie-2 ratios as predictors of prognosis in critically ill medical patients.

Study design: The study included 74 adults admitted to an intensive care unit (ICU). The patients were separated in two groups: Group A [sepsis: n=40] and Group B [no-sepsis: n= 34] patients. Serum levels of Ang-2 and Tie-2 were determined in the first 12 hours after admission and were correlated with ICU severity scores, APACHE II, SOFA and SAPS and with the death rate.

Results: Group A gave significantly higher values (p=0.01), for serum Ang-2 (11.07±9.21 ng/ml) compared to Group B (6.18±5.28 ng/ml). The level of Tie-2 was also higher (11.03±5.12 ng/ml) in Group A compared to Group B (9.46±4.99 ng/ml) (p=0.19). In Group A, the Ang-2/Tie2 ratio showed higher values than Group B (p=0.02). There was a positive association between severity scores (APACHE II, SAPS, and SOFA) and Ang-2, and Ang-2/ Tie-2 ratio, but not for Tie2.

Conclusions: In our study Ang-2 and Ang-2/Tie-2 ratio serum levels had independent diagnostic value in patients with sepsis, as measured on admission.

Open access

Zsombor Mathe, Razvan Constantin Serban, Irina Pintilie, Cristina Somkereki, Adina Hutanu and Alina Scridon

Abstract

Introduction: The magnitude of the very early coronary artery bypass grafting (CABG)-related inflammatory response has been shown to influence post-CABG outcomes. However, the dynamics of the systemic inflammatory response to CABG beyond the very early postoperative phase and its relevance to clinical outcomes are not fully understood.

Methods: Circulating levels of several inflammatory markers were determined in 30 consecutive patients undergoing elective isolated on-pump CABG one day prior (D0-1), and 2 (D2) and 5 days post-CABG.

Results: CABG was associated with a significant increase in all studied inflammatory marker levels (all p<0.05 for D2 versus D0-1). D2 post-CABG IL-6 and IL-8 levels were both significantly positively correlated with extracorporeal circulation (ECC) and aortic clamping (AC) times (all p<0.05), whereas a weaker correlation was observed between D2 post-CABG IL-8 levels and total surgery time (r=0.42, p=0.02). In multiple regression analysis, D2 IL-8 levels independently predicted post-CABG kidney (p= 0.02) and liver (p = 0.04) dysfunction, as well as a sum of post-CABG major complications ≥2 (p = 0.04).

Conclusions: In this prospective study, longer duration of cardiopulmonary bypass caused a larger post-CABG inflammatory surge, whereas the duration of total CABG surgery had a less significant effect. IL-8 hyperresponders had greater risk of developing kidney and liver dysfunction and presented more major post-CABG complications. These data suggest that targeting the IL-8 pathway using antiinflammatory agents, or simply by shortening the duration of cardiopulmonary bypass could improve the in-hospital post-CABG outcomes in this population.