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Introduction: This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra‐amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms‐like tyrosine kinase‐1 (sFlt‐1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. Material and methods: This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra‐amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra‐amniotic inflammation (by amniotic fluid interleukin‐6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt‐1 and PlGF were assessed using the Elecsys® sFlt‐1 and Elecsys® PlGF immunoassays and converted into multiples of medians. Results: Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt‐1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt‐1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. Conclusions: Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra‐amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion. [ABSTRACT FROM AUTHOR]

Objective: To determine the concentration of interleukin-6 (IL-6) in the cervical fluid in women with spontaneous preterm labor with intact fetal membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation), or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone). Methods: Eighty women with singleton pregnancies complicated by PTL between gestational ages 22 + 0 and 34 + 6 weeks were included in this retrospective cohort study. Samples of amniotic and cervical fluids were collected at the time of admission. Amniotic fluid samples were obtained via transabdominal amniocentesis, and cervical fluid was obtained using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on the combination of culture and molecular biology methods. The concentration of IL-6 in the amniotic and cervical fluids were measured using an automated electrochemiluminescence immunoassay method. Intra-amniotic inflammation was defined as an amniotic fluid IL-6 concentration 3000 pg/mL. Results: The presence of intra-amniotic infection and sterile inflammation was identified in 15% (12/80) and 26% (21/80) of the women, respectively. Women with intra-amniotic infection (median: 587 pg/mL; p = .01) and with sterile intra-amniotic inflammation (median: 590 pg/mL; p = .005) had higher concentrations of IL-6 in the cervical fluid than those without intra-amniotic inflammation (intra-amniotic infection: median 587 pg/mL vs. without inflammation, median: 136 pg/mL; p = .01; sterile intra-amniotic inflammation, median: 590 pg/mL vs. without inflammation, p = .005). No differences were found in the concentrations of IL-6 in the cervical fluid between women with intra-amniotic infection and sterile intra-amniotic inflammation (p = .81). Conclusion: In pregnancies with PTL, both forms of intra-amniotic inflammation are associated with elevated concentrations of IL-6 in the cervical fluid. [ABSTRACT FROM AUTHOR]

Positive effects of dexrazoxane (DEX) in anthracycline cardiotoxicity have been mostly assumed to be associated with its iron-chelating properties. However, this explanation has been recently questioned. Iron plays also an important role in the catecholamine cardiotoxicity. Hence in this study, the influence of DEX on a catecholamine model of acute myocardial infarction (100 mg/kg of isoprenaline by subcutaneous injection) was assessed: (i) the effects of an intravenous dose of 20.4 mg/kg were analyzed after 24 h, (ii) the effects were monitored continuously during the first two hours after drug(s) administration to examine the mechanism(s) of cardioprotection. Additional in vitro experiments on iron chelation/reduction and influence on the Fenton chemistry were performed both with isoprenaline/DEX separately and in their combination. DEX partly decreased the mortality, reduced myocardial calcium overload, histological impairment, and peripheral haemodynamic disturbances 24 h after isoprenaline administration. Continuous 2 h experiments showed that DEX did not influence isoprenaline induced atrioventricular blocks and had little effect on the measured haemodynamic parameters. Its protective effects are probably mediated by inhibition of late myocardial impairment and ventricular fibrillation likely due to inhibition of myocardial calcium overload. Complementary in vitro experiments suggested that iron chelation properties of DEX apparently did not play the major role. Key words: dexrazoxane, catecholamine, iron, acute myocardial infarction, cardiotoxicity, isoprenaline, myocardium. Les effets positifs du dexrazoxane (DEX) sur la cardiotoxicite des anthracyclines ont surtout ete attribues a ses proprietes de chelateur de fer. Cette explication a cependant ete remise en question recemment. Le fer joue aussi un role dans la cardiotoxicite des catecholamines. C'est ainsi que dans cette etude, l'influence du DEX a ete evaluee dans un modele d'infarctus aigu du myocarde induit par les cathecolamines (100 mg/kg d'isoprenaline sous-cutane) : (i) les effets d'une dose intraveineuse de 20,4 mg/kg de DEX ont ete analyses apres 24 h et (ii) les effets ont ete suivis de maniere continue au cours des deux premieres heures suivant l'administration du ou des medicaments afin d'examiner les mecanismes responsables de cardioprotection. Des experiences additionnelles in vitro de chelation/reduction du fer et de l' influence sur la chimie de Fenton ont ete realisees avec l' isoprenaline et le DEX utilises separement ou conjointement. Le DEX diminuait partiellement la mortalite, reduisait la surcharge calcique de myocarde, les anomalies histologiques et les perturbations hemodynamiques peripheriques 24 h apres l' administration d' isoprenaline. Les experiences realisees en continu pendant les deux premieres heures ont montre que le DEX n' avait pas d' influence sur le blocage atrioventriculaire induit par l' isoprenaline et avait peu d'effet sur les parametres hemodynamiques mesures. Ses effets protecteurs sont probablement dus a l'inhibition des dysfonctions tardives du myocarde et de la fibrillation ventriculaire, vraisemblablement a cause d'une inhibition de la surcharge calcique du myocarde. Les experiences complementaires realisees in vitro ont suggere que les proprietes du DEX dans la chelation du fer ne jouaient apparemment pas le role principal. Mots-cles : dexrazoxane, catecholamine, fer, infarctus aigu du myocarde, cardiotoxicite, isoprenaline, myocarde. [Traduit par la Redaction], Introduction Dexrazoxane (DEX) is the only approved drug for the prevention of anthracycline cardiotoxicity, and few studies reported its positive effects on cardiac impairment caused by ischaemia-reperfusion or chronic catecholamine [...]

To determine the amniotic fluid glucose levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on the presence of microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. A total of 142 women with singleton pregnancies complicated by PPROM between gestational ages 24 + 0 and 36 + 6 weeks were included. Amniocentesis was performed at the time of admission. The assessments of microbial invasion of the amniotic cavity (using both cultivation and non-cultivation techniques) and intra-amniotic inflammation (amniotic fluid interleukin-6 levels ≥ 3000 pg/mL) were performed on all the women. Based on the presence of microbial invasion of the amniotic cavity and/or intra-amniotic inflammation, the women were further categorized into the subgroups: (i) intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation); (ii) sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation without microbial invasion of the amniotic cavity); (iii) colonization (the presence of microbial invasion of the amniotic cavity without intra-amniotic inflammation); and (iv) negative amniotic fluid (the absence of either microbial invasion of the amniotic cavity or intra-amniotic inflammation). Amniotic fluid glucose levels were assessed using enzymatic reference method with hexokinase. There was a difference in the amniotic fluid glucose levels among the women with intra-amniotic infection, sterile intra-amniotic inflammation, colonization, and those with negative amniotic fluid (p <.0001). No difference was found in the amniotic fluid glucose levels between women with intra-amniotic infection and those with sterile intra-amniotic inflammation [infection: median 11.6 mg/dL (0.7 mmol/L) vs. sterile: median 6.3 mg/dL (0.4 mmol/L); p =.41] and between women with colonization and negative amniotic fluid [colonization: median 21.6 mg/dL (1.2 mmol/L) vs. negative: median 23.4 mg/dL (1.3 mmol/L; p =.67]. Women with intra-amniotic infection and sterile intra-amniotic inflammation had lower amniotic fluid glucose levels than women with colonization and with negative amniotic fluid in crude analysis as well as after adjustment for gestational age at sampling. Amniotic fluid glucose level of 10 mg/dL (0.56 mmol/L) was the optimal concentration for the identification of intra-amniotic inflammation in women with PPROM. The presence of intra-amniotic inflammation was associated with lower amniotic fluid glucose levels in singleton pregnancies complicated with PPROM. An amniotic fluid glucose level of 10 mg/dL (0.56 mmol/L) was the optimal concentration for the identification of intra-amniotic inflammation in PPROM pregnancies. In the absence of better amniotic fluid markers, amniotic glucose could be used as a marker of intra-amniotic inflammation, with very good specificity in PPROM pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method. Study Design: This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit. Results: Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908–0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799–0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045. Conclusion: While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to compare the amniotic fluid interleukin (IL)-6 concentrations measured using the automated electrochemiluminescence immunoassay method and ELISA, and to establish an IL-6 concentration cut-off value for intra-amniotic inflammation (IAI) in preterm prelabor rupture of membranes (PPROM), which can be used in the automated electrochemiluminescence immunoassay method.Materials and methods: A total of 120 women with PPROM were included in this study. Amniotic fluid samples were obtained through transabdominal amniocentesis. IL-6 concentrations were assessed using both the automated electrochemiluminescence immunoassay method and ELISA, the current gold standard. IAI was defined as an amniotic fluid IL-6 concentration of ≥2600 pg/mL measured using ELISA.Results: A correlation between both assays was found (Spearman's rho = 0.97; p < .0001). Based on the receiver-operating characteristic curve for the identification of IAI (area under the curve = 0.99), a cut-off value of ≥3000 pg/mL was selected for the automated electrochemiluminescence immunoassay method with a sensitivity of 88%, specificity of 99%, positive predictive value of 97%, negative predictive value of 96%, and likelihood ratio of 76.Conclusions: For amniotic fluid IL-6 concentrations assessed using the automated electrochemiluminescence immunoassay method, a cut-off value of 3000 pg/mL was indicated for diagnosing IAI in women with PPROM. [ABSTRACT FROM AUTHOR]

Background. Predicting cardiovascular events remains challenging despite the range of known biomarkers. Aim. To establish relationships between various biochemical and functional parameters of the cardiovascular system. Method. The relationship between cardiovascular dys/function and various biomarkers was examined in 145 experimental rats half of which received isoprenaline 100 mg/kg s.c. to induce cardiac impairment. Results. Serum concentration of cardiac troponin T (cTnT), a known marker of cardiac derangement, correlated strongly with degree of myocardial injury (e.g. calcium overload, stroke volume) but correlations between cTnT and oxidative stress parameters were weak (for glutathione and vitamin C) or not found (for serum vitamin E and plasma thiobarbituric acid reactive substances levels). Relationships between cTnT and other parameters were exponential with the exception of myocardial calcium, where a power function was found.Conclusions. Commonly used biomarkers of oxidative stress cannot reliably predict cardiovascular dys/function in experimental rats. [ABSTRACT FROM AUTHOR]

An abstract of the medical research "Dose-Dependence Study of a Novel Iron Chelator PCTH in a Model of Catecholamine Cardiotoxicity," by Zuzana Bobrovova, Radomir Hrdina, Premysl Mladenka, Mojmir Hubl, Jaroslava Vavrova, Magdalena Holeckova, Vladimir Palicka is presented.

Introduction: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively., Methods: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays., Results: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p &lt; 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p &lt; 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL., Conclusion: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days., (© 2024 The Author(s). Published by S. Karger AG, Basel.)