Marcel Stanciu

Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects

OBJECTIVES Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF). DESIGN AND METHODS We studied 27 patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically. RESULTS CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P=0.001). CONCLUSIONS Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma with/without Hashimoto's thyroiditis

Abstract Objective. To investigate the potential role of interleukin 4 (IL-4), interleukin 10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without Hashimotos thyroiditis (HT). Methods. Eighty consecutive patients (64 F/16 M, 43.2 ± 12.7 years) with PTC and 40 (37 F/3 M, 40.6 ± 12.3 years) with papillary thyroid carcinoma associated with Hashimotos thyroiditis (PTC + HT) were evaluated before radioiodine therapy. A control group of 20 patients with HT without thyroid cancer (18 F/2 M, 47.3 ± 2.8 years) was included in the study for the comparison of cytokine levels. Results. No meaningful differences were found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45% persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in patients with persistent/recurrent disease compared to those without recurrence (p < 0.001). IL-4, IL-10 and hs-CRP were also found in substantially higher concentrations in PTC + HT patients with persistent/recurrent disease than in patients with HT or PTC (with or without recurrence) (p < 0.01). Positive correlations were observed between IL-4, IL-10, hs-CRP and thyroglobulin (Tg) (r between 0.48 and 0.56, p < 0.005) or antithyroglobulin antibodies (TgAb) (r between 0.63 and 0.80, p < 0.002) in PTC and PTC + HT patients with persistent/recurrent disease. Conclusions. Increased levels of serum IL-4, IL-10 and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT patients. Our results suggest that these biomarkers might be used to improve patient stratification according to the risk of recurrence, especially in patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.

Imbalance between Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Promotes Invasion and Metastasis of Head and Neck Squamous Cell Carcinoma

BACKGROUND The balance between collagenolysis and its inhibition is critical during extracellular matrix remodeling in head and neck squamous cell carcinoma (HNSCC). An imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) plays a critical role in the development of tumor cell invasion and metastasis. The purpose of the study was to determine MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in the sera of patients with HNSCC in relation to clinicopathological parameters. METHODS Serum samples from seventy patients with HNSCC were measured by ELISA, before and 2 days after surgery. Forty healthy volunteers were selected as controls. RESULTS Preoperative MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were significantly higher in HNSCC patients than in the control group (p < 0.001 and p = 0.002, respectively). Changes in MMP-9 concentration and MMP9/TIMP-1 ratio after surgery had a negative correlation with lymph node involvement (r = - 0.35, p = 0.021 and r = - 0.37, p = 0.013), while changes in TIMP-1 had a positive one (r = 0.45, p = 0.006). Histological grade was positively correlated with the changes in circulating TIMP-2 level (r = 0.39, p = 0.021). No significant correlation was discovered between MMP-2/TIMP-2 ratio and tumor grade or any clinicopathological variables. CONCLUSIONS Our results suggest that an imbalance between MMP-9 and TIMP-1 could play an important role in metastatic spread via lymphatic pathways of HNSCC cells. MMP-9/TIMP-1 ratio and, in particular, MMP-9, TIMP-1, TIMP-2, may represent suitable biomarkers for early diagnosis and detection of disease progression and dissemination in HNSCC patients.

Effects of thyroid hormone withdrawal on natriuretic peptides during radioactive iodine therapy in female patients with differentiated thyroid cancer

Abstract Objective: We aimed to investigate the effects of thyroid hormone withdrawal on N-terminal prohormone forms of atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (NT-proBNP) during radioiodine therapy in female patients with differentiated thyroid cancer (DTC). Methods: Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), NT-proANP and NT-proBNP were measured in 51 female patients with DTC (48.7 ± 4.2 years) at three time-points: day of radioiodine therapy (t1 – under acute hypothyroidism), 5 days after radioiodine (t2 – under acute hypothyroidism) and 3 months after radioiodine (t3 – under TSH suppression). Thirty healthy euthyroid women served as controls (42.8 ± 5.6 years). Results: At t1/t2/t3, median NT-proANP was 5.2/1.7/487 pmol/L vs. 297.7 pmol/L in control group (p < 0.001), median NT-proBNP was 50.1/36.5/79.5 pmol/L vs. 64.5 pmol/L (p < 0.001) and median NT-proANP/NT-proBNP ratios was 0.20/0.18/4.81 vs. 4.14 (p < 0.001). In acute hypothyroidism, FT3 levels were positively correlated with NT-proANP (r = 0.38, p = 0.005), NT-proANP/NT-proBNP ratios (r = 0.47, p = 0.001), heart rate (r = 0.39, p = 0.005), and negatively with mean arterial blood pressure (r = −0.58, p < 0.001). Conclusions: Our results indicate that NT-proANP reflects more accurately direct thyroid hormone effects than NT-proBNP. Thyroid hormone-dependent hemodynamic effects seem to be overlapped on the direct stimulatory effect of thyroid hormones on NT-proANP secretion by cardiac myocytes.

Serum Level of Matrix Metalloproteinase-9 in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is characterized by the upregulation of a large number of matrix metalloproteinases (MMPs). The aim of the study was to investigate the level of MMP-9 in the sera of HNSCC patients and its relationship to clinicopathological features. METHODS Serum samples from sixty-five patients (56M/9F, 59.11 ± 9.02 years) with HNSCC were quantitatively measured by ELISA assay, before and two days after surgery. Forty healthy volunteers served as controls (29M/ 11F, 56.21 ± 12.13 years). RESULTS Median serum concentrations of MMP-9 were consistently upregulated in HNSCC patients both preoperatively (1593.0 ng/mL, IQR: 833.0 - 1942.0 ng/mL) and postoperatively (1382.0 ng/mL, IQR: 778.6 - 2062.0 ng/mL) in comparison to healthy controls (291.3 ng/mL, IQR: 223.8 - 330.5 ng/mL) (p < 0.001). Pretreatment levels of MMP-9 were related to the size of primary tumor (p = 0.018) and lymph node involvement (p = 0.045). No statistically significant association was found between serum MMP-9 concentrations and clinical stage or degree of differentiation of the tumor cells. CONCLUSIONS Serum MMP-9 level could be used as a diagnostic tool for early detection of HNSCC and for determining prognosis. Moreover, our results suggest that MMP-9 might be a good marker in evaluating the size of the primary tumor and lymph node involvement. Further studies are needed to show whether MMP-9 could serve as a marker for recurrence.

ECG monitoring. A software tool for deriving time and frequency parameters

In this paper is presented a software application which performs dynamic analysis of ECG tachogram using time framing (data windows) and appropriate sliding steps, as chosen by investigator. The application provides a high degree of versatility and the paper presents the algorithms, some experimental results and their significance.

The role of pro-fibrotic biomarkers in paroxysmal and persistent atrial fibrillation

Purpose Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin‐6 (IL‐6), transforming growth factor‐beta1 (TGF‐&bgr;1), matrix metalloproteinase‐9 (MMP‐9), tissue inhibitor of metalloproteinase‐1 (TIMP‐1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) and left atrial (LA) diameter. Methods Thirty‐seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. Results IL‐6 levels and MMP‐9/TIMP‐1 ratio were significantly higher in AF patients than in non‐AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT‐proBNP and LA diameter. In contrast, TGF‐&bgr;1 levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9–87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9–43.6 pg/mL in persistent AF). TGF‐&bgr;1 was negatively correlated with NT‐proBNP (r = −0.53, P = .001 in paroxysmal AF and r = −0.71, P < .001 in persistent AF) and LA diameter (r = −0.44, P = .006 in paroxysmal AF and r = −0.51, P = .003 in persistent AF). Conclusions Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT‐proBNP, IL‐6 and MMP‐9/TIMP‐1 ratio. Moreover, this study suggests that the relationship between TGF‐&bgr;1, NT‐proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF‐&bgr;1 signaling pathway. HighlightsAF progression is associated with a gradual increase in NT‐proBNP, IL‐6, MMP‐9/TIMP‐1.TGF‐&bgr;1 was lower in persistent AF than in paroxysmal AF and non‐AF controls.TGF‐&bgr;1 was negatively correlated with NT‐proBNP and LA diameter in AF.AF progresses despite compensatory changes in the TGF‐&bgr;1 signaling pathway.

Design of a current sensor based on optical fibers

This paper present the design of a current sensor based on Faraday Effect using optical fibers devices and a polarizing beam splitter (PBS). Two different schematics are to be taken into account, for high currents and for smaller ones. A single polarized laser signal is sent to the PBS prism and two angular components are separated. From here, these optical signals are processed using some interfaces, a NI-DAQ acquisition board and a LabVIEW interface. After calculations, the unknown current is obtained function of the reflexion angle between the two light components.

NT-proBNP and CA 125 levels are associated with increased pro-inflammatory cytokines in coronary sinus serum of patients with chronic heart failure

Purpose Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino‐terminal fragment of the prohormone B‐type natriuretic peptide (NT‐proBNP) and CA‐125 production and release in chronic HF (CHF). We aimed to measure the levels of NT‐proBNP, CA 125, pro‐anti‐inflammatory cytokines (IL‐6, IL‐1&bgr;, IL‐8, TNF‐&agr; and IL‐4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. Methods We enrolled 32 subjects (20M/12F) with CHF (III‐IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. Results All investigated biomarkers were significantly higher in CHF patients than in non‐CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT‐proBNP, IL‐6 and IL‐1&bgr; levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT‐proBNP, CS IL‐6 and CS IL‐1&bgr; serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = −0.61, P < 0.001; r = −0.71, P < 0.001 and r = −0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL‐1&bgr; (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL‐6 (r = 0.43, P = 0.015), TNF‐&agr; (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT‐proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). Conclusions CS sampling of NT‐proBNP, CA 125 and pro‐anti‐inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT‐proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation. HighlightsNT‐proBNP, IL‐6, IL‐1&bgr; were higher in CS than in PV, while CA 125 was lower.A strong relationship was found between CS NT‐proBNP, CS IL‐6, CS IL‐1&bgr; and LVEF.CA 125 concentrations were closely related to IL‐1&bgr; in serum sampled from CS.PV CA 125 was correlated with PV IL‐6, PV TNF‐&agr; and LVEF.CA 125 was positively correlated with NT‐proBNP both in CS and PV.