Examination of inflammatory markers pentraxin 3, cyclophilin A and heparin-binding epidermal growth factor in patients with acute myocardial infarction with ST-elevation

Poznato je da je koronarna arterijska bolest (KAB) povezana sa inflamatornim i oksidativnimprocesima koji dovode do okluzije koronarnih arterija i akutnog koronarnog sindroma, najčešćeinfarkta miokarda sa ST-elevacijom (STEMI). Još uvek se traga za biomarkerima koji bi bili korisni uklasifikaciji bolesnika prema težini bolesti i u predviđanju budućih srčanih događaja. Svrha ove studijeje da se ispitaju koncentracije pentraksina 3 (PTX3), ciklofilina A (CyPA) i heparin-vezujućegepidermalnog faktora rasta (HB-EGF) kod bolesnika sa STEMI (N=87) u odnosu na zdrave osobe(N=193) i bolesnike sa stabilnom anginom pektoris (N=15) kako bi se utvrdilo da li su promene ovihparametara posledica hronične srčane bolesti ili im se vrednosti menjaju usled akutnih poremećaja uSTEMI. Dodatno je analizirano da li primena primarne perkutane koronarne intervencije (pPCI) dovodido oštećenja krvnih sudova srca što će se manifestovati kroz promenu u koncentracijama navedenihispitivanih parametara. Ovi parametri su analizirani i kod bolesnika sa dijagnozom infarkta miokardabez opstrukcije koronarnih arterija (MINOCA). Studija je pokazala da su inflamatorni biomarkeriPTX3 i HB-EGF povišeni u STEMI i da se značajno menjaju posle pPCI kod bolesnika saopstruktivnom KAB u poređenju sa vrednostima pre procedure. MINOCA bolesnici imali su značajnoviše vrednosti PTX3 u odnosu na bolesnike sa STEMI. Kako bi se ispitali nezavisni prediktori visokihkoncentracija PTX3 i HB-EGF kod bolesnika sa STEMI, primenjena je faktorska analiza. Faktormetaboličko-oksidativnog stresa je značajan prediktor visokih koncentracija PTX3, dok je PTX3značajan prediktor visokih koncentracija HB-EGF. Osim toga, rezultati su pokazali da je identifikacijaMINOCA etiologije ključna za lečenje ovih bolesnika u čemu, pored standardnih procedura, možepomoći određivanje koncentracije PTX3.Since the association of coronary artery disease (CAD) with inflammatory and oxidativeprocesses that leads to the development of coronary artery occlusion and acute coronary syndrome,most commonly in the form of ST-elevation myocardial infarction (STEMI) have been recognized,biomarkers that would be useful in classifying patients according to disease severity and in predictingfuture cardiac events are still being sought. This study aimed to examine the concentrations ofpentraxin 3 (PTX3), cyclophilin A (CyPA) and heparin-binding epidermal growth factor-like growthfactor (HB-EGF) in patients with STEMI (N = 87) compared to healthy subjects (N = 193) and patientswith stable angina pectoris (N = 15) to determine whether changes in these parameters are due tochronic heart disease or their values change due to acute disorders in STEMI. It was additionallyanalyzed whether the application of primary percutaneous coronary intervention (pPCI) leads todamage of the heart blood vessels, which will be manifested as a change in the concentrations of theexamined parameters. These parameters were also analyzed in patients with the diagnosis of themyocardial infarction without coronary artery obstruction (MINOCA). This study showed that theinflammatory biomarkers PTX3 and HB-EGF are elevated in STEMI and change significantly afterpPCI in patients with obstructive CAD compared to pre-procedure values. MINOCA patients hadsignificantly higher PTX3 values compared to patients with STEMI. Factor analysis was applied toexamine independent predictors of high PTX3 and HB-EGF concentrations in patients with STEMI.The metabolic-oxidative stress factor is a significant predictor of high concentrations of PTX3, whilePTX3 is a significant predictor of high concentrations of HB-EGF. Besides, the results showed that theidentification of MINOCA etiology is crucial for the treatment of these patients in which thedetermination of PTX3 concentration can help, in addition to standard procedures

Examination of inflammatory markers pentraxin 3, cyclophilin A and heparin-binding epidermal growth factor in patients with acute myocardial infarction with ST-elevation

Poznato je da je koronarna arterijska bolest (KAB) povezana sa inflamatornim i oksidativnim procesima koji dovode do okluzije koronarnih arterija i akutnog koronarnog sindroma, najčešće infarkta miokarda sa ST-elevacijom (STEMI). Još uvek se traga za biomarkerima koji bi bili korisni u klasifikaciji bolesnika prema težini bolesti i u predviđanju budućih srčanih događaja. Svrha ove studije je da se ispitaju koncentracije pentraksina 3 (PTX3), ciklofilina A (CyPA) i heparin-vezujućeg epidermalnog faktora rasta (HB-EGF) kod bolesnika sa STEMI (N=87) u odnosu na zdrave osobe (N=193) i bolesnike sa stabilnom anginom pektoris (N=15) kako bi se utvrdilo da li su promene ovih parametara posledica hronične srčane bolesti ili im se vrednosti menjaju usled akutnih poremećaja u STEMI. Dodatno je analizirano da li primena primarne perkutane koronarne intervencije (pPCI) dovodi do oštećenja krvnih sudova srca što će se manifestovati kroz promenu u koncentracijama navedenih ispitivanih parametara. Ovi parametri su analizirani i kod bolesnika sa dijagnozom infarkta miokarda bez opstrukcije koronarnih arterija (MINOCA). Studija je pokazala da su inflamatorni biomarkeri PTX3 i HB-EGF povišeni u STEMI i da se značajno menjaju posle pPCI kod bolesnika sa opstruktivnom KAB u poređenju sa vrednostima pre procedure. MINOCA bolesnici imali su značajno više vrednosti PTX3 u odnosu na bolesnike sa STEMI. Kako bi se ispitali nezavisni prediktori visokih koncentracija PTX3 i HB-EGF kod bolesnika sa STEMI, primenjena je faktorska analiza. Faktor metaboličko-oksidativnog stresa je značajan prediktor visokih koncentracija PTX3, dok je PTX3 značajan prediktor visokih koncentracija HB-EGF. Osim toga, rezultati su pokazali da je identifikacija MINOCA etiologije ključna za lečenje ovih bolesnika u čemu, pored standardnih procedura, može pomoći određivanje koncentracije PTX3.Since the association of coronary artery disease (CAD) with inflammatory and oxidative processes that leads to the development of coronary artery occlusion and acute coronary syndrome, most commonly in the form of ST-elevation myocardial infarction (STEMI) have been recognized, biomarkers that would be useful in classifying patients according to disease severity and in predicting future cardiac events are still being sought. This study aimed to examine the concentrations of pentraxin 3 (PTX3), cyclophilin A (CyPA) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with STEMI (N = 87) compared to healthy subjects (N = 193) and patients with stable angina pectoris (N = 15) to determine whether changes in these parameters are due to chronic heart disease or their values change due to acute disorders in STEMI. It was additionally analyzed whether the application of primary percutaneous coronary intervention (pPCI) leads to damage of the heart blood vessels, which will be manifested as a change in the concentrations of the examined parameters. These parameters were also analyzed in patients with the diagnosis of the myocardial infarction without coronary artery obstruction (MINOCA). This study showed that the inflammatory biomarkers PTX3 and HB-EGF are elevated in STEMI and change significantly after pPCI in patients with obstructive CAD compared to pre-procedure values. MINOCA patients had significantly higher PTX3 values compared to patients with STEMI. Factor analysis was applied to examine independent predictors of high PTX3 and HB-EGF concentrations in patients with STEMI. The metabolic-oxidative stress factor is a significant predictor of high concentrations of PTX3, while PTX3 is a significant predictor of high concentrations of HB-EGF. Besides, the results showed that the identification of MINOCA etiology is crucial for the treatment of these patients in which the determination of PTX3 concentration can help, in addition to standard procedures

Effects of agmatine on chlorpromazine-induced neuronal injury in rat

This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/ kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control values in all of the examined brain regions. Western blot analysis supported biochemical findings in all groups, but the most notable changes were found in the hippocampus. Our results suggest potentially beneficial effects of agmatine, which may be useful in the modified antioxidant approach in chlorpromazine-therapy

Association of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein with the Extent of Coronary Stenosis in Patients Undergoing Coronary Angiography

Background: We compared factors of inflammation high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity. Methods: The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1-3), representing significant stenosis in one, two or three vessels. Results: We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1-3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1-3) patients (AUC=0.770, p lt 0.001). Conclusion: PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application

Examination of inflammatory markers pentraxin 3, cyclophilin A and heparin-binding epidermal growth factor in patients with acute myocardial infarction with ST-elevation

Poznato je da je koronarna arterijska bolest (KAB) povezana sa inflamatornim i oksidativnim procesima koji dovode do okluzije koronarnih arterija i akutnog koronarnog sindroma, najčešće infarkta miokarda sa ST-elevacijom (STEMI). Još uvek se traga za biomarkerima koji bi bili korisni u klasifikaciji bolesnika prema težini bolesti i u predviđanju budućih srčanih događaja. Svrha ove studije je da se ispitaju koncentracije pentraksina 3 (PTX3), ciklofilina A (CyPA) i heparin-vezujućeg epidermalnog faktora rasta (HB-EGF) kod bolesnika sa STEMI (N=87) u odnosu na zdrave osobe (N=193) i bolesnike sa stabilnom anginom pektoris (N=15) kako bi se utvrdilo da li su promene ovih parametara posledica hronične srčane bolesti ili im se vrednosti menjaju usled akutnih poremećaja u STEMI. Dodatno je analizirano da li primena primarne perkutane koronarne intervencije (pPCI) dovodi do oštećenja krvnih sudova srca što će se manifestovati kroz promenu u koncentracijama navedenih ispitivanih parametara. Ovi parametri su analizirani i kod bolesnika sa dijagnozom infarkta miokarda bez opstrukcije koronarnih arterija (MINOCA). Studija je pokazala da su inflamatorni biomarkeri PTX3 i HB-EGF povišeni u STEMI i da se značajno menjaju posle pPCI kod bolesnika sa opstruktivnom KAB u poređenju sa vrednostima pre procedure. MINOCA bolesnici imali su značajno više vrednosti PTX3 u odnosu na bolesnike sa STEMI. Kako bi se ispitali nezavisni prediktori visokih koncentracija PTX3 i HB-EGF kod bolesnika sa STEMI, primenjena je faktorska analiza. Faktor metaboličko-oksidativnog stresa je značajan prediktor visokih koncentracija PTX3, dok je PTX3 značajan prediktor visokih koncentracija HB-EGF. Osim toga, rezultati su pokazali da je identifikacija MINOCA etiologije ključna za lečenje ovih bolesnika u čemu, pored standardnih procedura, može pomoći određivanje koncentracije PTX3.Since the association of coronary artery disease (CAD) with inflammatory and oxidative processes that leads to the development of coronary artery occlusion and acute coronary syndrome, most commonly in the form of ST-elevation myocardial infarction (STEMI) have been recognized, biomarkers that would be useful in classifying patients according to disease severity and in predicting future cardiac events are still being sought. This study aimed to examine the concentrations of pentraxin 3 (PTX3), cyclophilin A (CyPA) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with STEMI (N = 87) compared to healthy subjects (N = 193) and patients with stable angina pectoris (N = 15) to determine whether changes in these parameters are due to chronic heart disease or their values change due to acute disorders in STEMI. It was additionally analyzed whether the application of primary percutaneous coronary intervention (pPCI) leads to damage of the heart blood vessels, which will be manifested as a change in the concentrations of the examined parameters. These parameters were also analyzed in patients with the diagnosis of the myocardial infarction without coronary artery obstruction (MINOCA). This study showed that the inflammatory biomarkers PTX3 and HB-EGF are elevated in STEMI and change significantly after pPCI in patients with obstructive CAD compared to pre-procedure values. MINOCA patients had significantly higher PTX3 values compared to patients with STEMI. Factor analysis was applied to examine independent predictors of high PTX3 and HB-EGF concentrations in patients with STEMI. The metabolic-oxidative stress factor is a significant predictor of high concentrations of PTX3, while PTX3 is a significant predictor of high concentrations of HB-EGF. Besides, the results showed that the identification of MINOCA etiology is crucial for the treatment of these patients in which the determination of PTX3 concentration can help, in addition to standard procedures

Da li pentraksin -3 doprinosi sniženju koncentracije lipoproteina niske gustine i terapiji statinima?

Statins have been shown to decrease inflammatory markers, especially high sensitivity C reactive protein (hsCRP), in a dose-dependent manner. Pentraxin-3 (PTX3) is another important inflammatory biomarker from the pentraxin family that provides useful prognostic information and facilitates diagnostics of cardiovascular diseases. This study investigated the effect of statin therapy on PTX3 and hsCRP concentrations and whether statins acted synergistically with PTX3 and hsCRP concentrations in lowering LDL-C. The study group consisted of 90 patients undergoing coronary angiography. The results showed that statins reduced PTX3 concentrations (p=0.031). PTX3 and hsCRP levels were significantly different between subclinical and severe stenosis groups (p=0.011 and p=0.009, respectively). Statin therapy was significantly associated with lower PTX3 and LDL-C levels in multiple logistic analyses. The probability that statin therapy would achieve target LDL-C values was highest in patients with low PTX3 values (OR=3.683, p=0.040), while multiplicative interaction was 23.3. The effect of statins on PTX3 reduction was higher than on hsCRP. It can be suggested that statin therapy was more successful in patients with low PTX3 values.Pokazano je da statini snižavaju koncentracije inflamatornih markera, posebno visoko osetljivog C reaktivnog proteina (hsCRP), pri čemu je sniženje zavisno od doze leka. Pentraksin- 3 (PTX3) je još jedan važan inflamatorni biomarker iz porodice pentraksina koji ima prognostičke karakteristike i olakšava dijagnozu kardiovaskularnih bolesti. U ovoj studiji je ispitivan efekat terapije statinima na koncentracije PTX3 i hsCRP, kao i sinergistički efekat terapije, koncentracija PTX3 i hsCRP u snižavanju LDL-C. U studiju je uključeno 90 pacijenata kojima je koronarnom angiografijom procenjeno suženje koronarnih krvnih sudova. Rezultati su pokazali da statini smanjuju koncentraciju PTX3 (p=0,031). Koncentracije PTX3 i hsCRP značajno se razlikuju između grupa sa subkliničkim (p=0,011) i teškim oblikom stenoze (p=0,009). Primenom multiple logističke regresione analize uočena je veza između terapije statinima i niskih koncentracija PTX3 i LDL-C. Verovatnoća da će terapija statinima postići ciljne vrednosti LDL- C bila je najveća kod pacijenata sa niskim vrednostima PTX3 (OR=3,683, p=0,040), dok je multiplikativna interakcija bila 23,3. Efekat statina na sniženje PTX3 bio je veći u odnosu na efekat koji ostvaruje na hsCRP. Može se sugerisati da je terapija statinima bila uspešnija kod pacijenata sa niskim vrednostima PTX3

Oxidative stress induced by chlorpromazine in patients treated and acutely poisoned with the drug

Background/Aim. Although chlorpromazine (CPZ) is an antipsychotic drug widely used in clinical practice for a long time, its mechanism of action has not been entirely defined. An extremely difficult managing of patients acutely poisoned with CPZ is additional reason for detailed studying its toxicity mechanisms. In this clinical study, we investigated whether the oxidative stress (OS) mediates CPZ toxic effects in the exposed patients. Methods. The patients were organized into 3 groups: the T-group - hospitalized patients receiving therapeutic doses of 75-150 mg CPZ/day; the overdosed group, divided into two subgroups: the group M and the group S - mildly (CPZ serum concentration: 0.21 ± 0.05 mg/L) and severely (CPZ serum concentration: 2.66 ± 0.25 mg/L) poisoned patients, respectively, and the group C (control group of healthy volunteers). Oxidative stress parameters [total antioxidative status (TAS) and malondialdehyde (MDA) in plasma)] and superoxide dismutase (SOD) activity in erythrocytes were measured spectrophotometrically, and CPZ concentrations in serum were monitored chromatographically. One set of measurements was performed in the group C and T, whereas two sets of measurements (after 24 hours and 48 hours) were done in the poisoned patients, groups M and S. Results. A decrease of TAS and increase of SOD activity were obtained in both subgroups of the poisoned patients, compared to the controls and the group receiving therapeutic doses of CPZ. A significant increase of MDA was achieved in severely poisoned patients, compared to all other groups. Conclusion. Changed oxidative stress parameters in patients poisoned with chlorpromazine indicate involvement of oxidative stress in the toxicity mechanism(s) of chlorpromazine. [Military Medical Academy, Project No. МФВМА/6/15-17

Oxidative Stress and Inflammatory Markers PTX3, CypA, and HB-EGF: How Are They Linked in Patients With STEMI?

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = −0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a “metabolic-oxidative stress factor” comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values