Influence of oral hormonal contraception on the concentration of anti-Müllerian and reproductive hormones in patients with polycystic ovary syndrome

Aim: To investigate the effects of three-month use of oral hormonal contraception (OHC) on hormonal status and ovarian reserve indicator (anti-Müllerian hormone, AMH) in patients with polycystic ovary syndrome (PCOS). Methods: 19 patients with diagnosed PCOS and clinical and laboratory signs of hyperandrogenism without additional comorbidities and co-medication were included in the study. All participants received therapy with the same oral hormonal contraceptive (fixed combination of 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate). The main outcomes were the concentrations of reproductive hormones measured before starting therapy and in the first cycle following therapy. Hormone concentrations were analysed using the immunochemical electrochemiluminescence (ECLIA) method. Results: Initial concentrations of total and free testosterone and AMH were elevated, while initial concentrations of other reproductive hormones were within reference values. By applying the therapy, the concentrations of AMH, luteinizing hormone (LH) and estradiol decreased by more than 20% and those of free testosterone by 85%. The concentration of sex hormone binding globulin (SHBG) increased by 44%. Conclusions: Three months of oral hormonal contraception with 35 μg ethinyl estradiol and 2 mg cyproterone acetate reduced elevated concentrations of AMH and free testosterone in PCOS patients. The decrease in serum AMH concentration indicates a temporary interruption of folliculogenesis as well as the selection of follicles from preantral to antral, and the decrease in androgens has a positive effect on the clinical condition and symptoms of patients with PCOS

Searching for carbonylome biomarkers of aging – development and validation of the proteomic method for quantification of carbonylated protein in human plasma

Aim To develop a method for measuring protein carbonylation in human plasma and serum samples, which was previously implied in numerous age-related phenotypes. Methods Protein expression and carbonylation were analyzed in plasma samples obtained from 12 healthy human individuals by using a novel method that combines affinity-based albumin and immunoglobulin G removal, and aminooxy dyeing in one- or two-dimensional gels. In addition, carbonylome profile of plasma and serum was compared. Coefficients of variation and intra-class correlation coefficients were used in statistical analysis. Results Following a step-wise laboratory development and optimization process, we measured the protein expression and carbonylation for 813 proteins from the plasma. The analysis of repeated measurements suggested excellent coefficients of variation, which rarely exceeded 10%. The average value of intra-class correlation based on absolute agreement (ICC) for protein expression was 0.97 ± 0.02, while for carbonylation it was 0.73 ± 0.24. The removal of the most extreme protein outlier in carbonylation assessment increased the average ICC to 0.87 ± 0.04. Low protein spot volume substantially reduced repeatability. Serum carbonylation estimates were similar to those from plasma, with the ICC in the range of 0.86-0.89. Conclusion We developed a reliable method for the measurement of human plasma protein carbonylation, which can be used for the assessment of carbonylome biomarkers of aging

Vasodilatation and antioxidant effects of phenolic acids from wine, heat-treated and intact wine in comparison with blackberry wine

Za razliku od ostalih polifenolnih spojeva iz vina i unatoč njihovoj velikoj zastupljenosti u drugim napitcima i hrani, biološki su učinci fenolnih kiselina slabije istraživani. Kardiovaskularni učinci termički obrađenog vina također do sada nisu istraživani, iako je primjena vina u kuhanju i konzumacija vina kao toplog napitka (kuhano vino) široko rasprostranjena. Osim vina iz grožđa, postoje brojna voćna vina čija je konzumacija sve popularnija, a njihovi su biološki učinci također slabije istraživani. Stoga je cilj ovog istraživanja bio utvrditi vazodilatacijske i antioksidacijske učinke fenolnih kiselina iz vina, termički obrađenog vina i kupinovog vina. Antioksidacijski učinci mjereni su FRAP (Ferric reducing antioxidant power) i TEAC (Trolox equivalent antioxidant capacity) metodama, dok je vazodilatacijska aktivnost određena na prekontrahiranim vaskularnim prstenovima aorte štakora i zamorčića. Fenolne kiseline bile su bolji antioksidansi nego vazodilatatori. Njihovi su antioksidacijski kapaciteti i maksimalni vazodilatacijski učinci pokazali negativnu povezanost. Kupinova su vina manje potentni vazodilatatori, a unatoč nižem sadržaju ukupnih fenola učinkovitiji antioksidansi u odnosu na crna vina. Vazodilatacijska aktivnost vina iz grožđa te kupinovih vina, osim s flavonoidnim i ukupnim fenolnim sadržajem, najznačajnije je povezana sa sadržajem antocijana, ali ne i sa sadržajem rezveratrola. Vazodilatacijski učinci crnog vina zagrijavanog pri 75 i 125 ºC uspoređivani su s učincima intaktnog vina i vina dealkoholiziranog bez termičkog stresa. Iako je pri najnižim koncentracijama dealkoholizirano vino ostvarilo jaču vazodilataciju, svi su uzorci vina postigli sličan maksimalni vazodilatacijski učinak, veći na aorti zamorčića.In contrast to other wine polyphenolic compounds, and despite their great abundance in other drinks and foods, biological effects of phenolic acids have been scarcely investigated. Also cardiovascular effects of thermally treated wine have not been investigated, although cooking with wine and consumption of mulled wine is common practice throughout the world. Besides grape wines, consumption of other fruit wines has become increasingly popular, but their biological effects have received little scientific attention. Therefore the aim of this study was to determine vasodilatory and antioxidant effects of wine phenolic acids, thermally treated and blackberry wine. Antioxidant effects were measured by FRAP (Ferric reducing antioxidant power) and TEAC (Trolox equivalent antioxidant capacity) methods. Vasodilatory effects were measured in the isolated rat and guinea pig aortic rings. Phenolic acids were better antioxidants than vasodilators. There was negative correlation between their antioxidant capacities and maximal vasodilatory effects. Blackberry wines were less potent vasodilators, and despite their lower total phenolic content, more effective antioxidants in comparison to red wines. Vasodilatory activity of grape and blackberry wines, in addition to their flavonoid and total phenolic content, was most significantly associated with their anthocyanins content. No association of vasodilation with the resveratrol content was found. Vasodilatory effects of red wine heated at 75 and 125 ºC were compared with the effects of the intact and wine dealcoholized without thermal stress. Although at the lowest concentrations dealcoholized wine produced greater vasodilation, all the tested wine samples produced similar maximal vasodilatory effect, more pronounced in the guinea pig aorta

Vasodilatation and antioxidant effects of phenolic acids from wine, heat-treated and intact wine in comparison with blackberry wine

Za razliku od ostalih polifenolnih spojeva iz vina i unatoč njihovoj velikoj zastupljenosti u drugim napitcima i hrani, biološki su učinci fenolnih kiselina slabije istraživani. Kardiovaskularni učinci termički obrađenog vina također do sada nisu istraživani, iako je primjena vina u kuhanju i konzumacija vina kao toplog napitka (kuhano vino) široko rasprostranjena. Osim vina iz grožđa, postoje brojna voćna vina čija je konzumacija sve popularnija, a njihovi su biološki učinci također slabije istraživani. Stoga je cilj ovog istraživanja bio utvrditi vazodilatacijske i antioksidacijske učinke fenolnih kiselina iz vina, termički obrađenog vina i kupinovog vina. Antioksidacijski učinci mjereni su FRAP (Ferric reducing antioxidant power) i TEAC (Trolox equivalent antioxidant capacity) metodama, dok je vazodilatacijska aktivnost određena na prekontrahiranim vaskularnim prstenovima aorte štakora i zamorčića. Fenolne kiseline bile su bolji antioksidansi nego vazodilatatori. Njihovi su antioksidacijski kapaciteti i maksimalni vazodilatacijski učinci pokazali negativnu povezanost. Kupinova su vina manje potentni vazodilatatori, a unatoč nižem sadržaju ukupnih fenola učinkovitiji antioksidansi u odnosu na crna vina. Vazodilatacijska aktivnost vina iz grožđa te kupinovih vina, osim s flavonoidnim i ukupnim fenolnim sadržajem, najznačajnije je povezana sa sadržajem antocijana, ali ne i sa sadržajem rezveratrola. Vazodilatacijski učinci crnog vina zagrijavanog pri 75 i 125 ºC uspoređivani su s učincima intaktnog vina i vina dealkoholiziranog bez termičkog stresa. Iako je pri najnižim koncentracijama dealkoholizirano vino ostvarilo jaču vazodilataciju, svi su uzorci vina postigli sličan maksimalni vazodilatacijski učinak, veći na aorti zamorčića.In contrast to other wine polyphenolic compounds, and despite their great abundance in other drinks and foods, biological effects of phenolic acids have been scarcely investigated. Also cardiovascular effects of thermally treated wine have not been investigated, although cooking with wine and consumption of mulled wine is common practice throughout the world. Besides grape wines, consumption of other fruit wines has become increasingly popular, but their biological effects have received little scientific attention. Therefore the aim of this study was to determine vasodilatory and antioxidant effects of wine phenolic acids, thermally treated and blackberry wine. Antioxidant effects were measured by FRAP (Ferric reducing antioxidant power) and TEAC (Trolox equivalent antioxidant capacity) methods. Vasodilatory effects were measured in the isolated rat and guinea pig aortic rings. Phenolic acids were better antioxidants than vasodilators. There was negative correlation between their antioxidant capacities and maximal vasodilatory effects. Blackberry wines were less potent vasodilators, and despite their lower total phenolic content, more effective antioxidants in comparison to red wines. Vasodilatory activity of grape and blackberry wines, in addition to their flavonoid and total phenolic content, was most significantly associated with their anthocyanins content. No association of vasodilation with the resveratrol content was found. Vasodilatory effects of red wine heated at 75 and 125 ºC were compared with the effects of the intact and wine dealcoholized without thermal stress. Although at the lowest concentrations dealcoholized wine produced greater vasodilation, all the tested wine samples produced similar maximal vasodilatory effect, more pronounced in the guinea pig aorta

Is the prolongation latency of visual evoked potentials a pathological sign in children with Down’s syndrome without ocular abnormalities? Case–control study of children with Down’s syndrome

Objective To evaluate retino-cortical function in children with Down’s syndrome (DS) and no evident ocular abnormalities beyond mild refractive error, by recording visual evoked potentials (VEP) in response to pattern-reversal stimuli and comparing to those of age-matched healthy controls.Methods and analysis All the children with DS registered at Split-Dalmatia County who met inclusion criteria of no ocular abnormalities and with refraction error between −0.5 and +2.0 D, and their age-matched healthy controls were included in the study (n=36 children, N=72 eyes, for both groups, respectively, with the same age of 9±2 years). Transient VEP was recorded and the waves with a positive peak as a response to a pattern-reversal stimulus, were analysed. The peak P100 latency, defined as the time from the stimulus onset to the main positive peak, and peak to peak amplitudes were measured.Results While P100 wave amplitudes were comparable between two groups (p=0.804), P100 latencies were from 4.3 to 28.5 ms longer in children with DS (p<0.001). Interocular latency difference between a VEP dominant and an inferior eye was pronounced in healthy (1.2 ms (0.2–4.0), but was almost diminished in children with DS (0.3 ms (0.1–0.5), p<0.001).Conclusion Our study has demonstrated that VEP response is divergent in children with DS compared with their age-matched healthy controls, indicating possible structural or functional abnormalities of the visual cortex. As VEP results are helpful in the diagnosis and treatment planning of vision-related disorders, we should reconsider the use of common VEP diagnostic criteria in subpopulation of children with DS

What Is the Smallest Change in Pulse Wave Velocity Measurements That Can Be Attributed to Clinical Changes in Arterial Stiffness with Certainty: A Randomized Cross-Over Study

Pulse wave velocity (PWV), a direct measure of arterial stiffness, is a promising biomarker of cardiovascular risk and a cardiovascular surrogate outcome. The resolution for detecting its smallest clinically significant change is dependent on the expected reproducibility, but there is currently no consensus on this. We estimated the PWV reproducibility in a range of intra-subject values that were observed over a 2 week period in a broad range of participants and under clinically relevant experimental conditions (two observers, morning/afternoon sessions, and number of visits) using SphygmoCor and Arteriograph devices. Each participant was recorded 12 times with each device over three visits, one week apart, and two morning and two afternoon recordings were taken per visit. The factors affecting reproducibility and the discrepancies between the consecutive PWV measurements for each device were also examined using multilevel mixed-effect models. We show that current PWV estimation guidance recommending 2 + 1 measurements is suboptimal because the PWV range was outside of the 1 m/s threshold for most of the participants, which is proposed as a minimal clinically important difference. The best reproducibility was yielded with median of four measurements and a 1.1 m/s threshold. Although PWV reproducibility and repeatability are frequently used interchangeably in studies, we demonstrated that despite their relative measures of variability (e.g., coefficient of variation) being comparable, their ranges revealed a clinically significant difference between them. We also found that different physiological variables were predictors of the discrepancy between the consecutive measurements made by the two devices, which is likely due to their distinct modes of operation. The evidence base for PWV reproducibility is limited, and more research is needed to deepen our understanding of the variation in arterial stiffness over time, as well as fluctuations within a population group and in an intervention setting

Effects of oxidation and browning of macerated white wine on its antioxidant and direct vasodilatory activity

Although naturally produced macerated white wines are increasingly popular, their biological effects are rarely studied. As wines containing no preservatives, they are highly susceptible to oxidation after bottle opening. Our aims were therefore: (1) to compare the antioxidant and direct vasodilatory activity of standard (W) and polyphenols-rich macerated white wine (PW); (2) to examine effects of oxidation and browning of PW, associated with its exposure to air for 24 (24 h-OxPW) and 48 h (48 h-OxPW), on measured biological activities. Total phenolics content, direct vasodilatory and antioxidant activity of PW were much higher than those of W. Overall effects of up to 48 h-exposure to air on levels and composition of examined phenolics were minor. Similarly, exposure to air and associated browning did not affect maximal vasodilatory and antioxidant activity of PW. Vasodilatory potency, however, increasingly weakened with exposure to air as oxidized samples had higher half maximal effective concentrations than intact PW

Genome-wide Association Study of Biochemical Traits in Korčula Island, Croatia

Aim To identify genetic variants underlying biochemical traits – total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, albumin, and fibrinogen, in a genomewide association study in an isolated population where rare variants of larger effect may be more easily identified. Methods The study included 944 adult inhabitants of the island of Korčula, as a part of larger DNA-based genetic epidemiological study in 2007. Biochemical measurements were performed in a single laboratory with stringent internal and external quality control procedures. Examinees were genotyped using Human Hap370CNV chip by Illumina, with a genome-wide scan containing 346 027 single nucleotide polymorphisms (SNP). Results A total of 31 SNPs were associated with 7 investigated traits at the level of P < 1.00 × 10−5. Nine of SNPs implicated the role of SLC2A9 in uric acid regulation (P = 4.10 × 10−6-2.58 × 10−12), as previously found in other populations. All 22 remaining associations fell into the P = 1.00 × 10−5-1.00 × 10−6 significance range.. One of them replicated the association between cholesteryl ester transfer protein (CETP) and HDL, and 7 associations were more than 100 kilobases away from the closest known gene. Nearby SNPs, rs4767631 and rs10444502, in gene kinase suppressor of ras 2 (KSR2) on chromosome 12 were associated with LDL cholesterol levels, and rs10444502 in the same gene with total cholesterol levels. Similarly, rs2839619 in gene PBX/knotted 1 homeobox 1 (PKNOX1) on chromosome 21 was associated with total and LDL cholesterol levels. The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen. Conclusion Although this study was underpowered for most of the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, replications of previous findings and consistency of association between the identified variants and more than one studied trait make such findings interesting for further functional follow-up studies. Changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in much larger samples in outbred populations

Subpopulations of white blood cells.

<p>Subpopulations of white blood cells.</p