Acute Vascular Response to Hemodialysis as Measured by Serum Syndecan-1 and Endothelin-1 Levels as Well as Vascular Stiffness.

BACKGROUND: Chronic hemodialysis (HD) patients have a very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. The aim of this article is to study the acute vascular changes during HD. METHODS: In 29 consecutive chronic HD patients (age: 65.6 ± 10.4 years), their pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. RESULTS: Their SDC-1 levels increased during HD (p = 0.004). Males had higher ET-1 levels. The patients were divided into two groups based on their pre-HD pulse wave velocity (PWV): PWV ≥ 12 m/s and PWV < 12 m/s. The pre-HD and mid-HD SDC-1 levels were higher in the group with a PWV ≥ 12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/mL, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/mL, p = 0.044, respectively). The post-HD ET-1 levels were higher in the patient group with a PWV ≥ 12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients with a PWV ≥ 12 m/s had higher pre-HD peripheral and aortic systolic blood pressures (p < 0.05). The total cholesterol correlated with the SDC-1 decrease during HD (r = 0.539; p = 0.008). The pre-, mid-, and post-HD SDC-1 correlated with ultrafiltration (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). CONCLUSION: SDC-1 and ET-1 contribute to the vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

Thrombocytes and Platelet-Rich Plasma as Modulators of Reproduction and Fertility.

Thrombocytes play an essential role in hemostasis and thrombosis. Moreover, the controlled activation of thrombocytes is required in reproduction and fertility. The platelet-activating factor and the controlled activation of platelets have important roles in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets accumulate in the follicular vessels surrounding the follicle and, due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters), locally increase oocyte maturation and hormone secretion. Furthermore, activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Low-dose aspirin can prevent OHSS during ovulation induction, while intrauterine or intraovarian administration of platelet-rich plasma (PRP) increases the endometrium thickness and receptivity as well as oocyte maturation. Activated thrombocytes rapidly release the contents of intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of thrombocytes, it is reasonable to suppose a platelet-associated regulatory system (PARS) in reproduction. Although we are far from a complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilization are promising.

Disrupted Balance of the Oxidant-Antioxidant System in the Pathophysiology of Female Reproduction: Oxidative Stress and Adverse Pregnancy Outcomes.

The significance of oxidative stress in the pathophysiology of male reproductive processes has been closely studied in the last two decades. Recently, it has become clear that oxidative stress can lead to numerous pathological conditions during female reproductive processes as well, contributing to the development of endometriosis, polycystic ovary syndrome and various forms of infertility. During pregnancy, physiological generation of reactive oxygen species (ROS) occurs in association with several developmental processes including oocyte maturation and implantation. An overproduction of ROS can lead to disturbances in fetal development and increases the risk for missed abortion, intrauterine growth restriction, pre-eclampsia, premature delivery and gestational diabetes. Our review focuses on the etiological role of the disrupted oxidant-antioxidant system during human gestation as it relates to adverse pregnancy outcomes.

Pathomechanisms of Prenatally Programmed Adult Diseases.

Based on epidemiological observations Barker et al. put forward the hypothesis/concept that an adverse intrauterine environment (involving an insufficient nutrient supply, chronic hypoxia, stress, and toxic substances) is an important risk factor for the development of chronic diseases later in life. The fetus responds to the unfavorable environment with adaptive reactions, which ensure survival in the short run, but at the expense of initiating pathological processes leading to adult diseases. In this review, the major mechanisms (including telomere dysfunction, epigenetic modifications, and cardiovascular-renal-endocrine-metabolic reactions) will be outlined, with a particular emphasis on the role of oxidative stress in the fetal origin of adult diseases.

Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization.

This study aimed to evaluate the interrelationship between telomere length, telomerase activity and oxidative DNA damage in patients undergoing in vitro fertilization (IVF). This single-center, observational clinical study comprised 102 unselected, consecutive patients with various infertility diagnoses. Granulosa cells (GCs) and follicular fluid (FF) were analyzed simultaneously for telomere functions and for the marker of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG). An Absolute Human Telomere Lengths Quantification qPCR Assay kit and Telomerase Activity Quantification qPCR Assay kit (Nucleotestbio, Budapest, Hungary), as well as an 8-OHdG ELISA kit (Abbexa Ltd., Cambridge, United Kingdom) were used for analyses. Similar telomere lengths were found in GCs and FF, however telomerase activity was markedly depressed, while 8-OHdG levels were markedly elevated in FF compared with those in GCs (p < 0.01). Telomere lengths were independent of telomerase activity both in GCs and FF. However, GC 8-OHdG was inversely related to telomerase activity in GCs and FF (p < 0.05). Importantly, 8-OHdG levels both in GCs and FF had significant negative impact on the number of the retrieved and MII oocytes (p < 0.01), whereas FF 8-OHdG was negatively related further to the number of fertilized oocytes and blastocysts (p < 0.01). In conclusion, we could not confirm the direct association of telomere function and reproductive potential. However, oxidative DNA damage, as mainly reflected by 8-OHdG, adversely affected early markers of IVF outcome and clinical pregnancies.

Oxidative Stress in Assisted Reproductive Techniques, with a Focus on an Underestimated Risk Factor.

Based on current findings, the presence of oxidative stress has a significant impact on the quality of gametes and embryos when performing assisted reproductive techniques (ART). Unfortunately, in vitro manipulation of these cells exposes them to a higher level of reactive oxygen species (ROS). The primary goal of this review is to provide a comprehensive overview of the development of oxidative stress in female and male reproductive systems, as well as in the case of the pre-implantation embryo and its environment. This review also focuses on the origins of ROS and the mechanisms of oxidative stress-induced damage during ART procedures. A well-known but underestimated hazard, light exposure-related photo-oxidation, is particularly concerning. The effect of oxidative stress on ART outcomes, as well as the various strategies for preventing it, are also discussed. We emphasize the role and significance of antioxidants and light protection including forms, functions, and mechanisms in the development of gametes and embryos in vivo and in vitro.

The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.

Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.

The role of platelets in reproduction / A thrombocyták szerepe a reprodukcióban

It is well known that platelets play a major role in hemostasis and thrombosis. Beyond these classic functions, the controlled activation of platelets is required in reproduction and immune response. In this review, we attempt to summarize the most important roles of thrombocytes in reproduction. The most recent studies of thrombocyte research provide remarkable insights into the physiological and clinical importance of this cellular fragment. We have summarized the key findings we have taken from the relevant literature ­ including our previous publications ­ and emphasized their significance. The plateletactivating factor and the controlled activation of platelets have important role in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Lowdose aspirin can prevent OHSS during ovulation induction, while intrauterine infusion of plateletrich plasma (PRP) increases the endometrium thickness and receptivity. Activated platelets rapidly release the contents of preformed intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of platelets, it is reasonable to suppose a plateletassociated regulatory system (PARS) in reproduction. Several studies prove the importance of thrombocytes in various essential physiological processes including reproduction. Although we are far from the complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilisation are promising.

Tissue Sodium Accumulation: Pathophysiology and Clinical Implications.

Excessive sodium intake has been well established as a risk factor for the development and progression of cardiovascular and renal diseases. Its adverse effects are achieved by renal sodium retention and related volume expansion and by inducing low-grade inflammation and oxidative stress (OS) in the target tissues. This review presents the recent concept of nonosmotic sodium storage in the skin interstitium, the subsequent dissociation of sodium and volume homeostasis, and the cellular response to the increased tissue sodium concentration. Furthermore, data are shown on the sodium barrier and buffering potential of the endothelial glycocalyx that may protect the functional integrity of the endothelium when it is challenged by an increased sodium load. Finally, examples will be given of the involvement of oxygen free radicals (OFR) in sodium-induced tissue damage, and some clinical entities will be mentioned that are causally associated with sodium/volume retention and OS.

Cardiometabolic Effects of Irisin in Patients with End-Stage Renal Disease on Regular Hemo- or Peritoneal Dialysis.

INTRODUCTION: Data on the role of irisin in vascular calcification in patients with end-stage renal diseases on regular dialysis are inconsistent, and the underlying mechanisms are not clearly defined. The present study was designed to explore the association of serum irisin with vascular stiffness and with the impact of well-established risk factors. METHODS: The clinical study enrolled 52 hemodialysis (HD) and 15 continuous ambulatory peritoneal dialysis (PD) patients with an age of >18 years receiving dialysis therapy for >3 months. Patients who had major pathologies affecting carbohydrate, lipid, and bone metabolism and those who had acute cardiovascular events were excluded. Thirty-seven healthy subjects matched for age and sex served as controls. Routine biochemical parameters were measured in fasting serum samples by standard methods. Serum irisin was determined using the commercial ELISA kit (BioVendor Laboratory Medicine Inc., Brno, Czech Republic). Arterial stiffness parameters - carotid-femoral pulse wave velocity (cf PWV) and augmentation index (Aix) - were measured using applanation tonometry (SphygmoCor System; AtCor Medical, Sydney, Australia). Body composition was assessed by segmental bioelectric impedance (InBody 2.0; Biospace Co. Ltd., Seoul, Korea). RESULTS: It was demonstrated that serum irisin levels were markedly depressed (p < 0.05), while the cf PWV significantly increased (p < 0.05) in HD/PD patients as compared to controls. Serum irisin proved to be independent of serum insulin, glucose, and HOMA-IR. However, it was inversely related to HbA1c (ß = -0.544, p = 0.035), iPTH (ß = -0.260, p = 0.035), and alkaline phosphatase (r = -0.325, p = 0.007). Furthermore, significant negative relationships were found of irisin to serum triglyceride and indices of body fat mass. Retrospective analysis at a follow-up period of 40 months revealed a direct relationship of irisin to all-cause mortality (p = 0.039). CONCLUSIONS: Our study demonstrated that serum irisin levels are reduced in uremic patients on regular HD/PD but failed to establish significant associations of irisin deficiency with vascular stiffness. However, the significant negative relationship of irisin to HbA1c, iPTH, and alkaline phosphatase suggests that it improves insulin sensitivity, inhibits bone resorption, mitigates bone-vascular interaction, and protects vascular function.

Key to Life: Physiological Role and Clinical Implications of Progesterone.

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means "promoting gestation", this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.

Expression of mRNAs for pro-and anti-apoptotic factors in granulosa cells and follicular fluid of women undergoing in vitro fertilization. A pilot study.

BACKGROUND: This observational clinical study evaluated the expression levels and predictive values of some apoptosis-related genes in granulosa cells (GCs) and follicular fluid (FF) of women undergoing in vitro fertilization (IVF). METHODS: GCs and FF were obtained at oocyte retrieval from 31 consecutive patients with heterogeneous infertility diagnosis (age: 34.3 ± 5.8 years, body mass index: 24.02 ± 3.12 kg/m2, duration of infertility: 4.2 ± 2.1 years). mRNA expression of pro-apoptotic (BAX, CASP3, CASP8) and anti-apoptotic (BCL2, AMH, AMHR, FSHR, LHR, CYP19A1) factors was determined by quantitative RT-PCR using ROCHE LightCycler 480. RESULTS: No significant difference in GC or FF mRNA expression of pro- and anti-apoptotic factors could be demonstrated between IVF patients with (9 patients) or without (22 patients) clinical pregnancy. Each transcript investigated was detected in FF, but their levels were markedly reduced and independent of those in GCs. The number of retrieved oocytes was positively associated with GC AMHR (r = 0.393, p = 0.029), but the day of embryo transfer was negatively associated with GC LHR (r = - 0.414, p = 0.020) and GC FSHR transcripts (r = - 0.535, p = 0.002). When pregnancy positive group was analysed separately the impact of apoptosis- related gene expressions on some selected measures of IVF success could be observed. Strong positive relationship was found between gene expression levels of pro- and anti-apoptotic factors in GCs. CONCLUSION: Our study provides only marginal evidences for the apoptosis dependence of IVF outcome and suggests that the apoptosis process induces adaptive increases of the anti-apoptotic gene expression to attenuate apoptosis and to protect cell survival.

Investigations of follicular fluid biomarkers in patients undergoing / A tüszofolyadék biomarkereinek vizsgálata in vitro fertilizációs kezelésben részesült betegekben.

Összefoglaló. A szerzok ismertetik vizsgálataik eredményeit, melyeket a közelmúltban az in vitro fertilizációs kezelésben részesülo betegeikben a tüszofolyadék biomarkereinek analízisével értek el. A vizsgálatok célja annak feltárása volt, hogy az in vitro fertilizációs eljárás során a petesejtek aspirációjakor nyert tüszofolyadék-biomarkerek lokális/ovarialis vagy szisztémás eredetuek, és milyen összefüggést mutatnak az in vitro fertilizáció eredményességét jelzo paraméterekkel. Megerosítettük, hogy az autokrin/parakrin szerotoninrendszer már a fejlodés legkorábbi idoszakában is muködoképes, és mind az anyai szérum, mind a tüszofolyadék szerotoninszintje szignifikáns pozitív összefüggést mutatott az érett petesejtek számával és a klinikai terhességgel (ß = 0,447, p = 0,015, illetve ß = 0,443, p = 0,016). Az agyi eredetu neurotrofikus faktor (BDNF) esetében ilyen kapcsolat nem volt igazolható, de a tüszofolyadék BDNF- és szerotoninszintjei közötti pozitív korreláció (r = 0,377, p = 0,040) azt mutatja, hogy a két neurohormon 'feed-forward' (elorecsatoló ) szabályozása ovarialis szinten is muködik. A hypothalamicus kisspeptin esetében csupán a posztstimulációs anyai szérumhormonszint befolyásolta az érett petesejtek számát (ß = 0,398, p = 0,029). A triptofán-kinurenin-szerotonin rendszer elemzése azt mutatta, hogy kedvezobb in vitro fertilizációs kimenetel várható, ha a szerotonin-kinurenin egyensúly a szerotonin javára tolódik el. Az oxidatívstressz-markerek közül vizsgálták a DNS-károsodás biomarkerét, a 8-hidroxi-2'-deoxiguanozin és a totális antioxidáns-kapacitás szérum- és tüszofolyadékszintjeit, és megállapították, hogy mindkét marker kedvezotlenül befolyásolja az életképes embriók számát (r = 0,302, p = 0,027 és r = 0,268, p = 0,039). A protektív hatású szirtuinok - nikotinamid-adenin-dinukleotid-függo hiszton-deacetiláz fehérjék - közül a vizsgált szirtuin-1 és szirtuin-6 a szérumszintektol függetlenül kimutatható a tüszofolyadékban. Szignifikáns pozitív korreláció van a tüszofolyadék-szirtuin-6 és az érettpetesejt-szám (F = 6,609, p = 0,016), valamint a szérum-szirtuin-1 (F = 10,008, p = 0,005) és a szérum-szirtuin-6 (F = 5,268, p = 0,031) és a klinikai terhesség gyakorisága között. Eredményeink alapján megállapítható, hogy a tüszofolyadék biomarkereinek vizsgálata javíthatja az in vitro fertilizáció kimenetelének megítélését. Orv Hetil. 2021; 162(14): 523-529. Summary. This article outlines the result of recent studies on several follicular fluid biomarkers in patients undergoing in vitro fertilization. The aim of these studies was to investigate whether 1) the follicular fluid biomarkers in question are produced locally by the ovaries or they originate from the circulating plasma, 2) and to establish their association with parameters of in vitro fertilization outcome. It was confirmed that the autocrine/paracrine serotonin system is functional already at the earliest stage of development and both maternal serum and follicular fluid serotonin levels were positively related to the number of mature oocytes (ß = 0.447, p = 0.015 and ß = 0.443, p = 0.016, respectively) and clinical pregnancy (ß = 1.028, p = 0.047). Such associations for brain-derived neurotrophic factor (BDNF) could not be found, but BDNF and serotonin in the follicular fluid were closely related (r = 0.377, p<0.040) suggesting that the feed-forward regulation of these neurohormones is activated at ovarian level. The hypothalamic kisspeptin in the post-stimulation maternal serum also increased the number of mature oocytes (ß = 0.398, p = 0.029). Analysis of the tryptophan-kynurenine-serotonin system showed a more favourable in vitro fertilization outcome when the serotonin-kynurenine balance was shifted and serotonin predominated over kynurenine. The oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, an indicator of DNA damage and the total antioxidant capacity in follicular fluid and maternal serum had negative impact on the number of viable embryos (r = 0.302, p = 0.027 and r = 0.268, p = 0.039), respectively. The protective sirtuins - the nicotinamide adenine dinucleotide-dependent histone deacetylase proteins - could be detected in follicular fluid irrespective of their maternal serum levels. Significant positive relationship was demonstrated between follicular fluid sirtuin 6 and mature oocytes (F = 6.609, p = 0.016) as well as between serum sirtuin 1 (F = 10.008, p = 0.005) and serum sirtuin 6 (F = 5.268, p = 0.031) and the rate of clinical pregnancy, respectively. On the basis of these results, it can be concluded that measuring several follicular fluid biomarkers may improve the prediction of the outcome of in vitro fertilization. Orv Hetil. 2021; 162(14): 523-529.

L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice.

By 1980, it was thought that we already knew most of the major mechanisms regulating vascular tone. However, after the somewhat serendipity discovery that endothelium is involved in mediation of relaxation to acetylcholine, a whole new world opened up and we had to rewrite our concept regarding vascular function and its regulation (not to mention many other fields). The new player was an endothelium derived relaxing factor, which molecular constitution has been identified to be nitric oxide (NO). This review summarizes the major molecular steps concerning how NO is synthetized from L-arginine. Also, the fate of L-arginine is described via the arginase and methylation pathways; both of them are affecting substantially the level and efficacy of NO. In vitro and in vivo effects of L-arginine are summarized and controversial clinical findings are discussed. On the basis of the use of methylated L-arginines, the vasomotor effects of endothelial NO released to agonists and increases in flow/wall shear stress (a major biological stimulus) is summarized. In this review the role of NO in the regulation of coronary vascular resistance, hence blood flow, is delineated and the somewhat questionable clinical use of NO donors is discussed. We made an attempt to summarize the biosynthesis, role, and molecular mechanisms of endogenously produced methylated L-arginine, asymmetric dimethylarginine (ADMA) in modulating vascular resistance, affecting the function of the heart. Additionally, the relationship between ADMA level and various cardiovascular diseases is described, such as atherosclerosis, coronary artery disease (CAD), ischemia/reperfusion injuries, and different types of coronary revascularization. A novel aspect of coronary vasomotor regulation is identified in which the pericardial fluid ADMA and endothelin play putative roles. Finally, some of the open possibilities for future research on L-arginine-NO-ADMA signaling are highlighted.

Effects of perinatal factors on sirtuin 3, 8-hydroxy-2'- deoxyguanosine, brain-derived neurotrophic factor and serotonin in cord blood and early breast milk: an observational study.

BACKGROUND: The profile of sirtuin 3 (SIRT3), 8-hydroxy-2'-deoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) in cord blood and in early breast milk was studied and it was related to perinatal factors. 5-HT and BDNF signalling systems have been claimed to play a critical role in intrauterine development, postnatal adaptation and lactation. Since prematurity and Caesarean birth are frequently associated with inflammation and related oxidative stress, an attempt was made to reveal the adaptive changes of the protective SIRT3 and the complex interplay among these bioactive components in cord blood and early breast milk. METHODS: Three groups each consisting of 30 mothers were included in the study: mothers who underwent spontaneous vaginal birth at term (group I), Caesarean section at term (group II) and preterm birth (group III). Venous cord blood and early breast milk samples were collected for measuring the biomarkers. SIRT3, 8-OHdG, BDNF and 5-HT levels were determined by using commercially available ELISA kits. RESULTS: It was demonstrated that cord blood levels of SIRT3, BDNF and 5-HT were markedly reduced whereas those of 8-OHdG were significantly elevated after preterm birth when compared with birth at term. The Caesarean section was associated with a moderate decrease in BDNF and 5-HT, however, both SIRT3 and 8-OHdG remained unaffected. Breast milk levels of all biomarkers studied proved to be independent of their corresponding cord blood concentrations. In response to preterm birth breast milk SIRT3, 8-OHdG and 5-HT increased significantly, while a drastic fall occurred in BDNF. A significant positive relationship was found of 5-HT with SIRT3 and 8-OHdG irrespective of the gestational age and the mode of delivery. CONCLUSIONS: It is suggested that the selected biomarkers in the breast milk mostly derive from local production by the mammary glands and 5-HT may have an essential role in the control of this process.

Levels of total antioxidant capacity and 8-hydroxy-2'-deoxyguanosine of serum and follicular fluid in women undergoing in vitro fertilization: focusing on endometriosis.

This study was designed to evaluate the levels of oxidative stress (OS) markers, total non-enzymatic antioxidant capacity (TAC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the serum and follicular fluid (FF) of patients undergoing in vitro fertilization (IVF). The impact of these biomarkers on IVF outcome was also analysed. Samples were obtained from 61 patients (age: 36.40 ± 4.99 years; BMI: 22.54 ± 2.46; infertility: 3.7 ± 2.5 years [mean ± SD]) before and after controlled ovarian hyperstimulation (COH). Patients with and without endometriosis were also evaluated separately. TAC was quantified by enhanced chemiluminescence assay and 8-OHdG was measured by enzyme-linked immunosorbent assay. It was demonstrated that these biomarkers responded to COH differently. No relationship could be detected in their FF levels, although their cumulative serum levels were inversely related. Both FF TAC and FF 8-OHdG had a negative impact on the number of good quality embryos, but an effect of Serum TAC and 8-OHdG could not be observed. When women with and without endometriosis were evaluated separately, inconsistent results were obtained. However, women without endometriosis had higher levels of serum and FF TAC when they progressed to clinical pregnancy. Our findings support the notion that OS has an important contribution to the reproductive potential in IVF patients, the ideal biomarkers of outcome measures, however, need to be further explored.

Serum and follicular fluid levels of serotonin, kisspeptin, and brain-derived neurotrophic factor in patients undergoing in vitro fertilization: an observational study : Neurohormones in patients receiving IVF.

OBJECTIVE: This study aimed to examine the effect of interactions between serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and kisspeptin on the reproductive potential in women receiving in vitro fertilization (IVF). METHODS: Paired serum and follicular fluid (FF) samples were obtained from 30 consecutive patients receiving IVF. Primary and secondary outcome measures were the rate of chemical/clinical pregnancy and the number of mature oocytes and embryos, respectively. Serum and FF 5-HT, BDNF, kisspeptin, and platelet-activating factor (PAF) levels were measured by enzyme-linked immunosorbent assay. RESULTS: In response to ovarian hyperstimulation, serum 5-HT and kisspeptin levels significantly increased, whereas serum BDNF and PAF levels remained unchanged. These factors were detected in FF, but they were unrelated to serum levels. FF 5-HT and BDNF levels were positively correlated. Serum kisspeptin levels were negatively correlated with FF BDNF and serum and FF PAF levels. Women who were pregnant had significantly lower FF BDNF levels compared with women who were not pregnant (21.96±12.75 vs 47.63±52.90 µg/mL). Multivariate stepwise linear regression and logistic regression analyses showed that only 5-HT and kisspeptin improved IVF outcome. CONCLUSIONS: This study indicates a role of serotoninergic mechanisms in success of IVF, but the contribution of interacting neuropeptides requires additional investigation.

[New aspects of the pathomechanism of salt-sensitive hypertension]. / Új szempontok a sószenzitív hypertoniák patomechanizmusában.

This article shortly outlines the evolution of hypertonia from risk factors to end-organ damage. The pathogenetic role of salt intake is underlined and in the light of recent clinical and experimental observations, the importance of renal and extrarenal mechanism in the development of salt-sensitive hypertension is analysed. The generally accepted concept that the inefficient renal sodium excretion and the subsequent expansion of the extracellular space is the major factor in blood pressure elevation is challenged. Evidences have been provided that the retained sodium dissociates from the volume of extracellular space and, also from the blood pressure. It has been shown that the negatively charged macromolecules in the subcutaneous interstitium bind sodium ions in osmotically inactive form and store sodium reversibly. The local tissue hypertonicity induces monocytes/macrophages invasion and activation that causes increased expression of tonicity-responsive enhancer binding protein (TonEBP) and the secretion of vascular endothelial growth factor C that result in enhanced lymphangiogenesis. The expanded lymphatic system drains the excess sodium and volume back to the circulation. The reduction of buffer function of this system may contribute to the development or to worsening of hypertension. Similar buffer and barrier functions are attributed to the glycocalyx that covers the luminal surface of vascular endothelium. It is also recognised that the high sodium intake alone is an important pathogenetic factor in end-organ damage independent of hypertension. This may be accounted for by the induction and activation of Th17 cells as well as by the increased production of several pro-inflammatory and pro-fibrotic cytokines. Orv Hetil. 2019; 160(2): 43-49.

Serum and follicular fluid levels of sirtuin 1, sirtuin 6, and resveratrol in women undergoing in vitro fertilization: an observational, clinical study.

OBJECTIVE: This observational, clinical study was designed to assess the role of sirtuin 1 (SIRT1), sirtuin 6 (SIRT6), and resveratrol in in vitro fertilization (IVF). METHODS: Paired serum and follicular fluid (FF) samples were obtained from 30 consecutive patients (age: 36.43 ± 4.17 years, body mass index: 22.90 ± 2.05 kg/m2, duration of infertility: 5.10 ± 2.80 years) who received IVF treatment. SIRT1, SIRT6, and resveratrol levels were measured by enzyme-linked immunosorbent assay. RESULTS: Ovarian hyperstimulation resulted in significantly higher serum SIRT1 levels in pregnant women (8 patients) compared with non-pregnant women (22 patients). SIRT6 levels remained unchanged after ovarian hyperstimulation, but were significantly lower in pregnant women compared with non-pregnant women before and after hyperstimulation. Both SIRTs were detected in FF, but they appeared to be independent of their serum levels. After correction for confounders, FF SIRT6 levels were positively related to mature oocytes (F = 6.609), whereas serum SIRT1 and SIRT6 levels were related to clinical pregnancy (F = 10.008, F = 5.268, respectively). CONCLUSIONS: Our study shows that SIRT1 and SIRT6, but not resveratrol, are involved in human reproduction and they may have a role in oocyte maturation and clinical pregnancy in IVF.

The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis.

BACKGROUND/AIMS: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS) and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD). METHODS: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity - PWV, aortic augmentation index - AIx) were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney) and the routine latoratory test were completed with measurements of osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG) by using commercially available ELISA kits. 35 heathcare workers served as controls. RESULTS: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG). PWV was found to be independently associated only with OC (ß:-0.25, p<0.029) and age (r=0.411,p<0.000), but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI), OPG (age, BMI) and OP (LDL-cholesterol). CONCLUSION: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.