Liver damage profile in COVID-19 pregnant patients.

INTRODUCTION: SARS-CoV-2 unsparingly impacts all areas of medicine. Pregnant women are particularly affected by the pandemic and COVID-19 related liver damage seems to be another threat to maternal and fetal health. The aim of this study is to define liver damage profile including bile acids serum levels in COVID-19 pregnant patients and to determine predictors of disease aggravation and poor obstetrics outcomes. METHODS: This study has been carried out in the Obstetrics and Gynecology Department, at the National Medical Institute in Warsaw, Poland between 01.02.2021 and 01.11.2022 The study cohort comprises 148 pregnant patients with COVID-19 and 102 pregnant controls who has been tested negative for SARS-CoV-2. RESULTS: COVID-19 pregnant patients presented liver involvement at admission in 41,9%. Hepatotoxic damage accounted for 27 (19.85%), cholestatic type was diagnosed in 11 (8.09%) and mixed type of liver injury was presented in 19 (13.97%) of patients. Higher serum levels of AST, ALT, GGT, total bilirubin and bile acids as well as mixed type of liver injury at admission were correlated with severe form of an illness. AST and ALT above upper reference limit as well as hepatotoxic type of liver damage predisposed pregnant patients with COVID-19 to poor obstetrics outcomes. CONCLUSION: Hepatic damage in pregnant women with COVID-19 is a common, mild, transaminase-dominant, or mixed type of injury, and often correlates with elevated inflammatory markers. SARS-CoV-2 test should be performed as a part of differential diagnosis in elevated liver function tests. Although bile acids serum levels were commonly elevated they seems to be clinically irrelevant in terms of pregnancy outcomes. Video Abstract.

sFlT-1/PlGF ratio as a predictor of preeclampsia in COVID-19 pregnant patients.

The association between SARS-CoV-2 infection in pregnancy and preeclampsia is widely debated in numerous studies. The aim of our study was to investigate whether an increased sFlt-1/PlGF ratio is a good marker of preeclampsia in pregnant patients with COVID-19 infection. This single centre prospective study was conducted in the Department of Obstetrics and Gynaecology, at the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw. The study group consisted of 68 COVID-19 pregnant patients and 57 SARS-CoV-2 negative pregnant controls. Serum sFlt-1/PlGF ratio was assessed. The two groups did not differ in terms of the frequency of IVF, nulliparity, history of hypertension, pre-gestational diabetes and chronic kidney disease. The primary outcome was the diagnosis of preeclampsia. Preeclampsia was diagnosed in 10 patients in both groups. The sFlt-1/PlGF ratio higher than 38, considered highly suggestive of developing preeclampsia, was found in 20 patients in the COVID-19 group and 15 patients in the control group. The odds of developing preeclampsia in patients with sFlt-1/PlGF ratio > 38 was approximately 4-fold higher in COVID-19 group and 11-fold higher in controls. Sflt-1/PlGF ratio does not differ significantly between the SARS-CoV-2-positive and SARS-COV-2-negative pregnant patients. The sFlt-1/PlGF ratio > 38 is associated with higher odds of the diagnosis of preeclampsia in both of these groups, and therefore may serve as its marker regardless of COVID-19 infection status.

Meconium Proteins Involved in Iron Metabolism.

The lack of specific biological materials and biomarkers limits our knowledge of the mechanisms underlying intrauterine regulation of iron supply to the fetus. Determining the meconium content of proteins commonly used in the laboratory to assess the transport, storage, and distribution of iron in the body may elucidate their roles in fetal development. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and calprotectin were determined by ELISA in meconium samples obtained from 122 neonates. There were strong correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL (p < 0.05). Meconium concentrations of ferritin were several-fold higher than the concentrations of the other proteins, with the exception of calprotectin whose concentration was approximately three-fold higher than that of ferritin. Meconium ceruloplasmin concentration significantly correlated with the concentrations of MPO, NGAL, lactoferrin, and calprotectin. Correlations between the meconium concentrations of haptoglobin, transferrin, and NGAL may reflect their collaborative involvement in the storage and transport of iron in the intrauterine environment in line with their recognized biological properties. High meconium concentrations of ferritin may provide information about the demand for iron and its utilization by the fetus. The associations between ceruloplasmin and neutrophil proteins may indicate the involvement of ceruloplasmin in the regulation of neutrophil activity in the intrauterine environment.

The Impact of Platelet-Rich Plasma Application during Cesarean Section on Wound Healing and Postoperative Pain: A Single-Blind Placebo-Controlled Intervention Study.

Background/Objectives: The aim of this study was to evaluate if platelet-rich plasma (PRP) application into the wound during cesarean delivery improves wound healing and reduces pain in the postoperative period. Materials and Methods: A total of 46 patients undergoing cesarean section (CS) were included in this single-blind placebo-controlled intervention study: 23 women in the PRP group and 23 in the placebo group. Every patient was asked to evaluate pain by using the Visual Analogue Scale (VAS) immediately after surgery, as well as 6 and 12 h after the surgery. The use of analgetics was also recorded. The postoperative scar was assessed using the Patient and Observer Scar Assessment Scale (POSAS). Results: There was no case of wound dehiscence in either group. Significant differences between the groups in the scar quality assessment were detected in both patient and doctor POSAS results on days 8, 30 and 90 after surgery in the favor of the PRP group. There was no difference in the pain intensity assessment on the VAS recorded after surgery, but PRP patients required fewer paracetamol doses per day than the control group. Conclusions: PRP application during CS significantly improved wound healing in both short- and long-term assessment. Although it did not influence postoperative pain intensity, it may reduce the use of analgetics after surgery.

Links Between Vitamin D-Binding Protein, Alpha-1 Antitrypsin and Neutrophil Proteins in Meconium.

BACKGROUND/AIMS: Alpha-1 antitrypsin (AAT), vitamin-D binding protein (VDBP) and neutrophil granule proteins are specifically related to the neutrophil function and may be considered candidate biomarkers detected and measured in meconium (the first feces of newborn infants) as signals indicating abnormal processes in the fetal stage. Individual proteins found in meconium can be a source of information pertaining to the intrauterine metabolic processes. METHODS: Concentrations of AAT, VDBP, calprotectin, myeloperoxidase, lactoferrin and elastase were measured using ELISA tests in 80 meconium samples collected from 19 healthy, full-term neonates. RESULTS: The meconium concentrations of VDBP and AAT (mean±SD, [mg/g meconium]: 3.74±6.93, 3.72±1.79, respectively) were approximately 1000 times higher than those of the protein granule proteins calprotectin, myeloperoxidase, elastase and lactoferrin (mean ± SD, [µg/g meconium]: 285.7±215.8, 1.83±1.73, 1.72±2.70, 45.58±78.89, respectively). The correlation between VDBP and AAT was negative (r= - 0.40. p=0.000) and those between VDBP and calprotectin (r=0.38, p=0.000) and VDBP and myeloperoxidase (r=0.45, p=0.000) were positive. AAT was found to correlate positively with lactoferrin (r=0.38, p=0.000). CONCLUSION: The correlations between the concentrations of VDBP and AAT, and with neutrophil granule proteins observed in meconium indicate their functional relationship in the intrauterine environment of the developing fetus. Meconium can be seen as an apparently underutilized source of biomarkers for evaluation of metabolic processes specific to fetal development.

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

STUDY QUESTION: Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER: This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY: Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION: A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE: We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS: Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Meconium Transferrin and Ferritin as Markers of Homeostasis in the Developing Fetus.

The molecular mechanisms regulating homeostasis in the developing fetus have not been satisfactorily elucidated. Meconium contains substances accumulated in the fetal intestines. Measurements of transferrin and ferritin concentrations in meconium and assessment of transferrin-ferritin relationships could enhance knowledge about specific processes of the intrauterine period involving the two proteins and their effects on the development and growth of the fetus. Transferrin and ferritin concentrations were measured by ELISA in the homogenates of first meconium portions from 125 neonates. Higher birth weight was associated with lower ferritin concentrations in meconium (r = -0.22, p = 0.015). In neonates with a birth weight of more than 3750 g, there was a positive correlation between transferrin and ferritin concentrations (r = 0.51, p = 0.003). With meconium transferrin concentrations above 43.52 µg/g, a negative correlation between transferrin and ferritin was established (r = -0.37, p = 0.036), while with transferrin concentrations below 43.52 µg/g, the correlations between the birth weight and the meconium transferrin and ferritin concentrations were negative (r = -0.61, p < 0.001 and r = -0.43, p = 0.017, respectively). Measurements of transferrin and ferritin in meconium specimens create a new use for these common biomarkers to improve our understanding of the effects of homeostasis in utero on the fetal development and growth. Establishing reference ranges of meconium transferrin and ferritin concentrations and their association with the clinical parameters during pregnancy could aid in the assessment of the impact of intrauterine life on the health status of the neonate and its adaptation to extrauterine life.

The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms.

Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Risk of venous thromboembolism during the use of oral estrogen-progestogen hormone therapies in light of most recent research findings.

Two important studies evaluating the safety profile of oral estrogen-progestogen hormonal therapies conducted in standard clinical practice with respect to the venous system were recently published. A large prospective controlled cohort study (PRO-E2) based on the non-inferiority design has shown that the relative risk of developing venous thrombosis (VTE) in women using combined oral hormonal contraceptives (COHC) containing 17ß-estradiol (1.5 mg) and nomegestrol acetate (2.5 mg) (E2/NOMAC) was not statistically different from that in users of COHC containing ethinylestradiol and levonorgestrel (EE/LNG). The aim of the recently presented study was to compare the risk of VTE in patients treated with a product for oral continuous combined menopausal hormone therapy containing 1 mg of 17ß-estradiol and 100 mg of micronized progesterone (1 mgE2/100 mgP4) with patients taking conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA). The study was based on an analysis of records retrieved from a US health insurance database, and was therefore concerned the real-life clinical practice. The hazard ratio of VTE when comparing 1 mgE2/100 mgP4 with CEE/MPA was 0.70 (95% CI: 0.53-0.92). The difference was found to be statistically significant (p < 0.05). The rewieved studies provide further evidence that the use of hormones bioidentical with endogenous steroids in oral contraception and menopausal hormone therapy creates an opportunity to combine high efficacy with a favorable safety profile.

Absence of SARS-CoV-2 RNA in Peritoneal Fluid During Surgery in Pregnant Women Who Are COVID-19 Positive.

STUDY OBJECTIVE: Coronavirus disease 2019 (COVID-19) infection poses significant risks during surgical interventions. We investigated the intraperitoneal presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients who are COVID-19 positive. DESIGN: A prospective group study. SETTING: Department of Obstetrics and Gynecology designated for patients with COVID-19, Central Clinical Hospital of the Ministry of Interior, Warsaw. PATIENTS: Overall, 65 pregnant women with COVID-19 infection underwent cesarian section. The diagnosis was confirmed either by positive antigen test or by positive reverse transcriptase-polymerase chain reaction assay performed within no more than 13 days before the operation. INTERVENTIONS: On the day of the operation, a nasopharyngeal swab was taken, and peritoneal fluid was collected at the beginning of the operation. Both the nasopharyngeal swab and peritoneal fluid samples were tested for SARS-CoV-2. MEASUREMENTS AND MAIN RESULTS: A total of 65 pregnant women with COVID-19 infection were enrolled in the study. The SARS-CoV-2 ribonucleic acid test by nasopharyngeal swab produced positive results in 34 patients. In this group as well as in 31 nonconfirmed patients, all peritoneal fluid samples tested negative for SARS-CoV-2 ribonucleic acid. CONCLUSION: These results suggest a low risk of COVID-19 transmission from the peritoneal cavity at the time of laparoscopy or laparotomy.

Can aminopeptidase N determined in the meconium be a candidate for biomarker of fetal intrauterine environment?

AIM: To investigate possible association of aminopeptidase N/CD13 with other parameters of possible homeostatic mechanisms in meconium for potential use in identifying intrauterine environmental stress factors during fetal and perinatal life. METHODS: Aminopeptidase N/CD13 (APN/CD13), calprotectin (CAL), myeloperoxidase (MPO), ceruloplasmin (CER), lactoferrin (LF) and interleukin-8 (IL-8) were determined using ELISA kits in 115 meconium samples collected from 30 healthy full term neonates. RESULTS: Significant correlations were established between meconium APN/CD13 [µg/g] (mean ± SD, median, range: 2.88 ± 9.90, 0.94, 0.09-91.54) and MPO (r = 0.77, p = .0000), CER (r = 0.48, p = .0000), LF (r = 0.26, p = .005), IL-8 (r = 0.44, p = .00012) but no correlation of APN/CD13 vs CAL (r = 0.15, p > .05). With increased APN/CD13 concentrations there were increases (p < .05) in concentrations of MPO, CER, LF and L-8. CONCLUSIONS: Meconium APN/CD13 demonstrates characteristic associations with other proteins involved in the regulation of metabolic processes. The panel of APN/CD13, MPO, CER and LF may be candidate biomarker for disorders developing in utero which may have impact on health in later life.

Can variability of serum electrophoretic fractions during pregnancy provide knowledge about maternal and fetal health.

AIM: Characteristics of variability of concentrations total protein and its electrophoretic fractions in serum of healthy pregnant women between successive trimesters and post-partum for initial classification of proteins involved in specific metabolic processes associated with pregnancy. METHODS: Total serum protein concentrations were measured by biuret method and serum protein fractions were electrophoretically separated in 166 serum samples collected from healthy pregnant women in three trimesters of pregnancy (1st, n = 55; 2nd, n = 42; 3rd, n = 39) and in post-partum (n = 30), and in 20 samples from nonpregnant controls. RESULTS: Across pregnancy, there were gradual, but occurring at different rates, decreases over time in serum total protein, albumin and gamma globulins compared to controls (P < 0.05). In 1st trimester, serum concentrations of total protein, albumin and gamma globulins were <10% lower than in nonpregnant state, with further decreases in 2nd and 3rd trimesters and in post-partum. The concentrations of alpha-1-, alpha-2-, beta-1- and beta-2-globulins were elevated compared to controls (P < 0.05) with different dynamics of change and with the highest percentage increase for alpha-1-globulin. CONCLUSION: Pregnancy-associated alterations in the serum concentrations of total protein and in its individual electrophoretic protein fractions in each trimester of pregnancy and differences versus normal ranges in nonpregnant healthy females could be a simple screening method for classification useful laboratory parameters that help obstetricians and gynecologists to make multidirectional judgments about the state of health of pregnant women.

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature.

Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.

Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).

OBJECTIVES: To evaluate the effects of a combined Myo-inositol (MI) and D-chiro-inositol (DCI) therapy on the hormonal and metabolic parameters of women with PCOS. Prospective clinical study. Clinical Study registration number - EUPAS25705 Material and methods: Seventy women diagnosed with PCOS according to the Rotterdam criteria were enrolled in this study. Patients received a combined therapy of one tablet that contained 550 mg of inositol (myo-inositol (MI) and D-chiro-inositol (DCI) in a ratio of 10:1) twice a day for 6 months. At each of 3 visits, the body weight, height and BMI were all recorded; and serum levels of free testosterone (fT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and glucose with insulin during standard OGTT (75 g) were measured. Also at each visit, transvaginal ultrasonography and skin condition assessments were performed. RESULTS: Significant body weight reduction and decreases in fT, FSH, LH and insulin levels, as well as significant increase of serum SHBG concentrations were observed. Serum glucose levels during OGTT decreased after 6 months of treatment. Also, skin conditions improved after only three months of treatment. CONCLUSIONS: Combination of MI and DCI in a ratio 10:1 seems to be efficient in improving both metabolic and hormonal parameters in patients with PCOS.

Correlation between the concentrations of lactoferrin and neutrophil gelatinase-associated lipocalin in meconium.

Neutrophil gelatinase-associated lipocalin (NGAL) and lactoferrin (Lf) are among the key components of the innate immune system due to their ability to bind iron with high affinity and thus control inflammation. The aim of this study was to test the use of NGAL and LF measurements in meconium for the assessment of the intrauterine homeostasis. NGAL and Lf concentrations were measured using ELISA kits in all serial meconium portions (n = 81) collected from 20 healthy neonates. Mean ± SD meconium concentration of Lf was 45.07 ± 78.53 µg/g and more than 1000-fold higher compared with that of NGAL at 1.93 ± 2.46 ng/g. The correlation between the two proteins (r = 0.83, p < 0.0001) was found only for portions with Lf concentrations > 25 µg/g. High variability of NGAL and Lf concentrations in meconium and their correlations prove their key role as biomarkers of the fetal condition in utero. NGAL and Lf measured in meconium are candidate biomarkers for fetal iron status.

Relationships between meconium concentrations of acute phase proteins.

Meconium concentrations of naturally accumulated ceruloplasmin (CER), lactoferrin (LF), and neutrophil gelatinase-associated lipocalin (NGAL) and their relationships considered as a panel of acute phase proteins could be used for the assessment of fetal homeostasis. CER, LF and NGAL concentrations were measured using enzyme-linked immunosorbent assay kits in meconium portions (n = 80) collected from 19 healthy neonates. The coefficients of variation (CV) of the meconium LF (1.77) and NGAL (1.26) were about two-fold higher than that of CER (0.73) with significant (P < 0.05) correlations between all three parameters. The LF to NGAL ratio (CV = 0.67) correlated strongly with the CER concentrations (r = 0.39, P < 0.01). These correlations between CER, LF and NGAL concentrations suggest their combined involvement in the metabolic processes in the developing fetus.