LC/MS/MS assessment of changes in placental angiotensin I metabolism in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a condition characterized by high blood pressure and significant proteinuria in pregnant women. It affects about 7% pregnancies and can be cause of fetal and maternal morbidity and mortality. During pregnancy, a physiological overexpression of the Renin-Angiotensin System (RAS) components is observed, including increased plasma Ang II level. Dysregulation of RAS in placenta may contribute to preeclampsia and uterine growth retardation. The aim of the study was to evaluate the Ang I metabolism in human preeclamptic placentas and to compare to normal pregnancies condition. METHOD: Fragments of placental tissues were collected right after ceasarian section from PE and physiological pregnancies. Tissues were incubated in Krebs buffer in the presence of Ang I. Evaluation of Ang I metabolites in incubating fluid was performed by LC/MS/MS method. mRNA expression of main RAS components was measured by RT-PCR. RESULTS: Pattern of angiotensin metabolites did not differ between groups. The main products were Ang 1-7 and Ang II. Comparing to control group, more than 3-fold lower production of Ang II and Ang 1-7 in preeclampsia was observed. mRNA expressions of ACE and AT1 were significantly decreased in pre- eclamptic placentas, whereas higher expression of mRNA of ACE2 and MAS receptor were observed. CONCLUSIONS: Production of Ang 1-7 by PE placentas was significantly lower than in control group. Significantly decreased mRNA expression of ACE and AT1 receptor and lower production of Ang II in placentas of PE patients suggest that placental Ang II/ACE/AT1r pathway could be less important than Ang 1-7/ACE-2/MASr pathway in development of preeclampsia, but this requires further investigations.

Charge Neutral [Cu2L2] and [Pd2L2] Metallocycles: Self-Assembly, Aggregation, and Catalysis.

A range of morphologically distinct metallosupramolecular Cu(II) and Pd(II) complexes has been constructed, based on the tritopic ligand 1,1',1″-(benzene-1,3,5-triyl)tris(4,4-dimethylpentane-1,3-dione) (H3L). By control of the reaction conditions, it is possible to generate distinct coordination assemblies possessing either macrocyclic or polymeric structures and more importantly distinct activity in catalysis of the Suzuki-Miyaura cross-coupling.

First-trimester presentation of ultrasound findings in trisomy 13 and validation of multiparameter ultrasound-based risk calculation models to detect trisomy 13 in the late first trimester.

OBJECTIVES: To identify the most common ultrasound patterns of markers and anomalies associated with Patau syndrome (PS), to explore the efficacy of multiparameter sonographic protocols in detecting trisomy 13 (T13) and to analyze the influence of maternal age (MA) on screening performance. METHODS: The project was a prospective study based on singleton pregnancies referred for a first-trimester screening examination. The scan protocol included nuchal translucency (NT), fetal heart rate (FHR), secondary ultrasound markers [nasal bone (NB), tricuspid regurgitation (TR), ductus venosus reversed a-wave (revDV)] and major anomaly findings. RESULTS: The study population comprised 6133 pregnancies: 6077 cases of euploidy and 56 cases of T13. Statistically significant differences were found in MA, FHR, NT, absence of NB, presence of revDV, TR and single umbilical artery. Fourteen cases of T13 (25%) demonstrated no markers of aneuploidy. The best general detection rate (DR) (DR of 78.6% with an false positive rate (FPR) of 1.2%) was obtained for a cutoff of 1/300 utilizing the "NT+T13" algorithm. The logistic regression model revealed that the central nervous system (CNS) anomalies had the greatest odds ratio (of 205.4) for T13. CONCLUSIONS: The effectiveness of the multiparameter sonographic protocol used for T13 screening showed promising results in patients older than 36 years and suboptimal results in patients between 26 and 36 years old. When screening for T13 left heart defects, CNS anomalies, abdominal anomalies, FHR above the 95th percentile, increased NT, revDV and lack of NB should receive specific attention.

Early fetal cardiac scan as an element of the sonographic first-trimester screening.

Early fetal cardiac scan (EFCS) is becoming an increasingly common element of the first trimester ultrasound screening carried out at 11-14 gestational weeks. It offers the first possibility to detect congenital heart defects (CHD) or, in ambiguous cases, to identify those pregnancies where a more detailed cardiac scan would be required later in pregnancy. The size of the fetal heart at the end of the first trimester and the associated relatively low image resolution make it impossible to capture all cardiac data to inform the ultimate picture. However, even at this stage, cues of anatomical and functional abnormalities can be picked up, which suggest not only a CHD, but also a likelihood of cardiovascular symptoms typical of genetic disorders. EFCS should focus on cardiac position, atrioventricular (AV) connections, AV valve function, initial assessment of ventriculo-arterial (VA) connections and the presence of red flag signs in the three vessel and trachea view (3VTV). Proper use of color Doppler mapping makes it possible to overcome the low resolution of B-mode to a certain extent. Here we present our long-term experience in EFCS.

Dynamic polyimine macrobicyclic cryptands - self-sorting with component selection.

Self-assembling macrobicyclic cryptand-type organic cages display remarkable self-sorting behavior with efficient component selection. Making use of the dynamic covalent chemistry approach, eight different cages were synthesized by condensation of tris(2-aminopropyl)amine with structurally different dialdehydes. A series of self-sorting experiments were first carried out on simple dynamic covalent libraries. They reveal the influence of different structural features of the aldehyde components on the condensation with two triamine capping units. Subsequently, self-sorting experiments were performed on more complex systems involving several dialdehyde building blocks. Altogether, the results obtained describe the effect of the presence of a heteroatom, of electrostatic interactions, of delocalization and of the flexibility/stiffness of the propensity of a component to undergo formation of a macrobicyclic cage. In the presence of a catalytic amount of acid, the macrobicyclic structure undergoes dynamic component exchange.

Selective C70 encapsulation by a robust octameric nanospheroid held together by 48 cooperative hydrogen bonds.

Self-assembly of multiple building blocks via hydrogen bonds into well-defined nanoconstructs with selective binding function remains one of the foremost challenges in supramolecular chemistry. Here, we report the discovery of a enantiopure nanocapsule that is formed through the self-assembly of eight amino acid functionalised molecules in nonpolar solvents through 48 hydrogen bonds. The nanocapsule is remarkably robust, being stable at low and high temperatures, and in the presence of base, presumably due to the co-operative geometry of the hydrogen bonding motif. Thanks to small pore sizes, large internal cavity and sufficient dynamicity, the nanocapsule is able to recognize and encapsulate large aromatic guests such as fullerenes C60 and C70. The structural and electronic complementary between the host and C70 leads to its preferential and selective binding from a mixture of C60 and C70.

Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry.

We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines.