Ever since proteomics was proven to be capable of characterizing a large number of differences in both protein quality and quantity, it has been applied in various areas of biomedicine, ranging from the deciphering molecular pathogenesis of diseases to the characterization of novel drug targets and the discovery of potential diagnostic biomarkers. Indeed, the biomarker discovery in human plasma is clearly one of the areas with enormous potential. However, without proper planning and implementation of specific techniques, the efforts and expectations may very easily be hampered. Numerous earlier projects aimed at clinical proteomics, characterized by exaggerated enthusiasm, often underestimated some principal obstacles of plasma biomarker discovery. Consequently, ambiguous and insignificant results soon led to a more critical view in this field. In this article, we critically review the current state of proteomic approaches for biomarker discovery and validation, in order to provide basic information and guidelines for both clinicians and researchers. These need to be closely considered prior to initiation of a project aimed at plasma biomarker discovery. We also present a short overview of recent applications of clinical proteomics in biomarker discovery., V. Tambor ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3β-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3β-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question “Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?“ - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3β-hydroxysteroid dehydrogenase (3β-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone., a2_Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20α-dihydroprogesterone (Prog20α) and between Prog20α and progesterone within the maternal blood) indicate that the localization of individual types of 17β-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20α in maternal blood. Type 2 17β-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20α to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20α due to the effects of type 1, 5 and 7 17β-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor., M. Hill ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Acute myocardial infarction (AMI) is one of the leading causes of death among adults in older age. Understanding mechanisms how organism responds to ischemia is essential for the ischemic patient’s prevention and treatment. Despite the great prevalence and incidence only a small number of studies utilize a metabolomic approach to describe AMI condition. Recent studies have shown the impact of metabolites on epigenetic changes, in these studies plasma metabolites were related to neurological outcome of the patients making metabolomic studies increasingly interesting. The aim of this study was to describe metabolomic response of an organism to ischemic stress through the changes in energetic metabolites and aminoacids in blood plasma in patients overcoming acute myocardial infarction. Blood plasma from patients in the first 12 h after onset of chest pain was collected and compared with volunteers without any history of ischemic diseases via NMR spectroscopy. Lowered plasma levels of pyruvate, alanine, glutamine and neurotransmitter precursors tyrosine and tryptophan were found. Further, we observed increased plasma levels of 3-hydroxybutyrate and acetoacetate in balance with decreased level of lipoproteins fraction, suggesting the ongoing ketonic state of an organism. Discriminatory analysis showed very promising performance where compounds: lipoproteins, alanine, pyruvate, glutamine, tryptophan and 3-hydroxybutyrate were of the highest discriminatory power with feasibility of successful statistical discrimination., Martin Petras, Dagmar Kalenska, Matej Samos, Tomas Bolek, Miroslava Sarlinova, Peter Racay, Erika Halasova, Oliver Štrbák, Jan Stasko, Ludovit Musak, Michaela Skorvanova, Eva Baranovicova., and Obsahuje bibliografii
Milk production, plasma bovine somatotropin (bST) and insulin-like growth factor I (IGF-1) were measured in dairy cows following a single subcutaneous injection of a slowly released preparation of either recombinant enterokinase linker bST (somidobove: 640 mg) or recombinant methionyl bST (sometribove: 500 mg). There was a 3-7-fold increase in plasma bST concentrations during the first three postinjection hours in cows treated with both sometribove (from 3.4±0.8 to 11.2±3.0 ng ml-1) or somidobove (from 2.3±0.3 to 17.5±2.6 ng ml-1). In the next 8 days the bST concentration in the bST-treated cows varied, but was still significantly increased above the controls. In the following days, the concentrations of bST did not differ from the controls. Plasma concentrations of IGF-1 increased nearly 2-fold as early as 24 h following recombinant bST administration and then continued to rise so that by 48 h postinjection they were nearly four times higher (control 16.2, bST-treated 61.7 ng ml-1). From 48 h after sometribove injection, IGF-1 concentrations remained at a plateau (varying between 60.4 and 85.7 ng ml-1) till day 11. Then it decreased slowly, but still remained higher on day 14 than those in placebo-treated cows (44.4±17.8 ng ml-1 in bST-treated animals; 12.2±7.5 ng ml-1 in the controls). Although IGF-1 level was increasing in all bST-treated animals, the absolute IGF-1 increase was not related to the increase in milk production.
In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sust aining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3β-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5α/β-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus. and M. Hill ... [et al.].
In the present study changes of some blood parameters of wild female yellowfin seabream (Acanthopagrus latus) caught from Persian Gulf were assayed during reproductive cycle. Altogether, 120 female A. latus (15 each month) were captured monthly from October 2010 to May 2011 from the Mussa Creek in the north-west of Persian Gulf. Blood samples were collected from caudal vein; plasma was separated and kept at –80 °C till analysis. Total protein, glucose, cholesterol, triglyceride, electrolytes, calcium, sodium, chloride, magnesium, potassium plus hepatic enzymes, Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST), were assayed in plasma sample. Total protein and calcium increased parallel to ovarian development and decreased after spawning time. Cholesterol and triglyceride had a peak during vitellogenesis and decreased after spawning but glucose had a peak during spawning time. Most of the electrolytes (sodium, magnesium and potassium) did not show any significant changes during the reproductive cycle in A. Latus. AST reached a peak during final
maturation of ovaries but ALT did not show any significant difference during differentsampling times.Our findings showed that biochemical parameters could be used as indicators of physiological status during differentmaturation stage in this species.