Diagnostyczna przydatność detekcji genu RHD w osoczu ciężarnych w profilaktyce konfliktu matczyno-płodowego na tle antygenu D z układu Rh

Objectives: The aim of the study was analytical validation of prenatal noninvasive fetal RHD detection in maternal plasma and the preliminary assessment of its clinical utility. Introduction of this noninvasive test into routine diagnostic use is important for more rational and safe immunoprophylaxis. Material and methods: RHD gene was detected using real-time PCR. Primers and probes complementary to sequence on exons 7 and 10 were chosen. Samples with RHD-negative results were examined with additional tests to confirm the proper isolation of cell-free fetal DNA (cffDNA). For male fetuses, the presence of fetal DNA was confirmed by detection of the male genetic marker (SRY gene) using Quantifiler DuoR kit. In the case of SRY-negative result we used mini SGM test, which is based on the detection of short-tandem repeat polymorphism differences between maternal and fetal DNA. Results: Diagnostic accuracy of RHD test was 96.82%, while diagnostic value of SRY determination was lower (87.50%). Mini SGM test was able to confirm the presence of fetal DNA in 77% of the cases. Conclusions: Effectiveness of the proposed procedure of prenatal noninvasive RHD determination and cffDNA confirmation is high, on condition proper control samples and suitable verifying tests are used.Cel pracy: Celem badań była walidacja oraz wstępna ocena przydatności testu do prenatalnego określania genu RHD pochodzenia płodowego w osoczu ciężarnej w rutynowej praktyce laboratoryjnej i klinicznej. Wprowadzenie do diagnostyki nieinwazyjnych badań prenatalnych ma na celu bardziej racjonalne i bezpieczne stosowanie immunoprofilaktyki. Materiał i metody: Badanie genu RHD w osoczu ciężarnych wykonano techniką real-time PCR z zastosowaniem starterow i sond specyficznych do sekwencji eksonow 7 i 10 genu RHD. Wyniki ujemne badania na obecność genu RHD weryfikowano dodatkowymi testami, ktore miały na celu potwierdzenie udanej izolacji i obecności DNA płodowego w probce. W pierwszej kolejności wykonywano oznaczenie markera płci męskiej (genu SRY), ktore potwierdzało obecność płodowego DNA w przypadku płodow płci męskiej. Badanie wykonywano testem QuantifilerR Duo. Probki z ujemnym wynikiem poddawano dalszej analizie poprzez oznaczanie polimorfizmow typu STR (ang. short tandem repeat) metodą mini SGM, rożnicując DNA pochodzenia matczynego i płodowego. Wyniki: Dokładność diagnostyczna testu do oznaczania genu RHD w osoczu wynosiła 96,82%. Wartość diagnostyczna oznaczania genu SRY była niższa i wynosiła 87,50%. Testem mini SGM udało się znaleźć marker rożnicujący w 77% przypadkow. Wnioski: Opracowany algorytm badania DNA płodowego metodami biologii molekularnej ma wysoką wartość diagnostyczną przy wykrywaniu genu RHD w osoczu i potwierdzaniu obecności DNA płodowego oraz umożliwia weryfikację wynikow ujemnych, pod warunkiem zastosowania właściwych badań kontrolnych

Evaluation of antiarrythmic activity of novel imidazo[2,1-F]purine-2,4-dione and imidazolidine-2,4-dione derivatives with aminoalkyl moieties

The main goal of this study was to assess antiarrhythmic activity of novel aminoalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione exerting α1 and 5-HT1A receptors affinity. Tested compounds produced prophylactic and therapeutic antiarrhythmic activity in an adrenaline-induced model of arrhythmia. The strongest antiarrhythmic activity as well as the highest α1-adrenoreceptor affinity (Ki = 13.9 nM) was found for 5-methyl-5-phenyl-3-[3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl]-imidazolidine-2,4- dione (12). The results indicated a correlation between α1-adrenoreceptor affinities and antiarrhythmic activity

Evaluation of antiplatelet activity of novel guanidine derivatives in the aspects of their adrenergic receptor activity

Designed acetamide derivatives based on guanidine and various heteroaryl carboxylic acids, were preliminary in vitro study of their adrenergic receptor affinity and anti-plateled effects. The obtained results have showed that exchange of 2,6-dichloro-phenyl substituent of guanidine into heteroaryl moieties, caused the decrease of receptor affinity, especially for α1-adrenoceptors. The observed receptor profile of activity for α2BAR was not changed compared to α1-ARs. Moreover, the observed effects on platelet aggregation induced by sub-threshold concentration of collagen and adrenaline strongly suggested that antiaggregant effect of N- (diaminomethylene)-2-(pyridin-3-yl)acetamide and N-(diaminomethylene)-2-(pyridin-4-yl)acetamide depends on their α2B-ARs antagonistic activity

Preliminary evaluation of central nervous system activity of (E)-N-2-methyl-3-phenylprop-2-enyl ((E)-N- α-methylcinnamyl) derivatives of selected aminoalkanols

A series of (E)-α-methylcinnamyl derivatives of selected aminoalkanols was synthetized and evaluated for activity in central nervous system. All compounds were tested as anticonvulsants and one additionally in antidepressant- and anxiolytic-like assays. The compounds possessed pharmacophoric elements regarded as beneficial for anticonvulsant activity: hydrophobic unit and two hydrogen bonds donor/acceptor features. The compounds were verified in mice after intraperitoneal (i.p.) administration in maximal electroshock (MES) and subcutaneous pentetrazole (scPTZ) induced seizures as well as neurotoxicity assessments. Eight of the tested substances showed protection in MES test at the dose of 100 mg/kg. The derivative of 2 aminopropan-1-ol was also tested in 6-Hz test in mice i.p. and showed anticonvulsant activity but at the same time the neurotoxicity was noted. The derivative of 2-amino-1-phenylethanol which possessed additional hydrophobic unit in aminoalkanol moiety was tested in other in vivo assays to evaluate antidepressant- and anxiolytic-like activity. The compound proved beneficial properties especially as anxiolytic agent remaining active in four-plate test in mice at the dose of 2.5 mg/kg (i.p.). In vitro biotransformation studies of 2-amino-1-phenylethanol derivative carried out in mouse liver microsomal assay indicated two main metabolites as a result of aliphatic and aromatic hydroxylation or aliphatic carbonylation. To identify possible mechanism of action, we evaluated serotonin receptors (5-HT1A, 5-HT6 and 5-HT7) binding affinities of the compounds but none of them proved to bind to any of tested receptors

Chemically homogenous compounds with antagonistic properties at all α1\alpha_{1}-adrenoceptor subtypes but not β1\beta_{1}-adrenoceptor attenuate adrenaline-induced arrhythmia in rats

Studies proved that among all α1-adrenoceptors, cardiac myocytes functionally express only α1A- and α1B-subtype. Scientists indicated that α1A-subtype blockade might be beneficial in restoring normal heart rhythm. Therefore, we aimed to determine the role of α1-adrenoceptors subtypes (i.e. α1A and α1B) in antiarrhythmic effect of six structurally similar derivatives of 2-methoxyphenylpiperazine. We compared the activity of studied compounds with carvedilol, which is β1- and α1-adrenoceptors blocker with antioxidant properties.To evaluate the affinity for adrenergic receptors, we used radioligand methods. We investigated selectivity at α1-adrenoceptors subtypes using functional bioassays. We tested antiarrhythmic activity in adrenaline-induced (20 µg/kg i.v.), calcium chloride-induced (140 and 25 mg/kg i.v.) and barium chloride-induced (32 and 10 mg/kg i.v.) arrhythmia models in rats. We also evaluated the influence of studied compounds on blood pressure in rats, as well as lipid peroxidation. All studied compounds showed high affinity towards α1-adrenoceptors but no affinity for β1 receptors. Biofunctional studies revealed that the tested compounds blocked α1A- stronger than α1B-adrenoceptors, but except for HBK-19 they antagonized α1A-adrenoceptor weaker than α1D-subtype. HBK-19 showed the greatest difference in pA2 values - it blocked α1A-adrenoceptors around sevenfold stronger than α1B subtype. All compounds showed prophylactic antiarrhythmic properties in adrenaline-induced arrhythmia, but only the activity of HBK-16, HBK-17, HBK-18 and HBK-19 (ED50=0.18-0.21) was comparable to that of carvedilol (ED50=0.36). All compounds reduced mortality in adrenaline-induced arrhythmia. HBK-16, HBK-17, HBK-18 and HBK-19 showed therapeutic antiarrhythmic properties in adrenaline-induced arrhythmia. None of the compounds showed activity in calcium chloride- or barium chloride-induced arrhythmias. HBK-16, HBK-17, HBK-18 and HBK-19 decreased heart rhythm at ED84. All compounds significantly lowered blood pressure in normotensive rats. HBK-18 showed the strongest hypotensive properties (the lowest active dose: 0.01 mg/kg). HBK-19 was the only compound in the group, which did not show hypotensive effect at antiarrhythmic doses. HBK-16, HBK-17, HBK-18, HBK-19 showed weak antioxidant properties.Our results indicate that the studied 2-methoxyphenylpiperazine derivatives that possessed stronger α1A-adrenolytic properties (i.e. HBK-16, HBK-17, HBK-18 and HBK-19) were the most compounds in adrenaline-induced arrhythmia. Thus, we suggest that the potent blockade of α1A-receptor subtype is essential to attenuate adrenaline-induced arrhythmia

INSTRUMENTY POZATARYFOWE W HANDLU ROLNO-SPOŻYWCZYM WYBRANYCH KRAJÓW ROZWIJAJĄCYCH SIĘ

Under the conditions of steadily reducing tariffs on agri-food trade, the non-tariff measures (NTMs) can be used to protect national agricultural markets. Such measures are used by both developed countries and developing mainly in relation to agri-food international trade. The main objective of the research was to assess the quantitative use of non-tariff instruments in agri-food import of selected developing countries. The analysis confirmed that non-tariff measures are used in the agri-food imports by developing countries and that within broad group of NTMs the sanitary and phytosanitary measures and the technical barriers mainly applied

SYSTEM OF COMPETITION PAYMENTS IN AGRICULTURE AS A PROBLEM OF POLAND’S INTEGRATION WITH EUROPEAN UNION

In March 1999 Poland started officially negotiations about the accession to European Union. Fundamental condition of integration is to accept the so-called acquis communautaire by Poland. From one side the admission in UE means the acceptation of all duties, from the other - getting opportunity of taking economic results which can influence economic development in a longer time. The Polish negotiation position was planned to be introduced in November 1999. Poland expects free trade in food and agriculture and a system of structural funds and compensation payments as well as guaranteed adequate production quotas. The huge amount of regulations and the volume o f ELTs budget spent on agriculture make that the sector of economy becomes the most problematical part of negotiations. The UE meeting in Berlin was expected to be a point of introduction of the elements of new radical reform into Common Agricultural Policy (CAP). The reform could be connected with expense reduction on the food sector of economy and with changes in equalisation payments. In March 1999 the Agenda 2000, i.e. the financial plan for 2000 - 2006, was accepted. According to these regulations the cost o f CAP is going to rise from 42,7 milliards of euro to 43,7 milliards in 2003 and compensation payments from 20 to 30 milliards of euro. At the same time the Agenda 2000 does not anticipate Polish farmers to be covered by a system of compensation payments. This article is focused on system of compensation payments, on the method of its establishing and its results. It also tries to show why instrument is one of the basic matters for Polish negotiating group

Intensywność handlu rolno-żywnościowego wybranych regionalnych ugrupowań handlowych relacji Południe-Południe

The growing number of regional trade agreements is a characteristic feature of contemporary international trade relations. The developing countries are more and more involved in this process. Creating groups is associated with changes in the direction of trade flows. The main objective of the study is to identify the agri-food trade direction of the South-South regional trade groupings (CACM, CAN, EAC, MERCOSUR) taking into account selected indicators of regional trade interdependence. The agri-food trade in the all tested groupings was increasingly directed towards the member states rather than tertiary countries. The differences amongh the groups are related to changes in the direction of trade. Specialization of trade direction strengthened in the CACM and CAN countries, remained unchanged for the EAC countries, and declined in MERCOSUR. / Synopsis. Charakterystyczną cechą współczesnych międzynarodowych relacji handlowych jest rosnąca liczba regionalnych porozumień handlowych. W procesie tym coraz częściej uczestniczą kraje tzw. globalnego Południa. Utworzenie ugrupowania wiąże się między innymi ze zmianą kierunku przepływów handlowych. Głównym celem opracowania jest identyfikacja kierunku handlu rolno-żywnościowego regionalnych ugrupowań handlowych relacji Południe-Południe (CACM, CAN, EAC, MERCOSUR) w świetle wybranych wskaźników regionalnych współzależności handlowych. W wyniku przeprowadzonej analizy stwierdzono, że handel rolno-żywnościowy we wszystkich badanych ugrupowaniach w większym stopniu ukierunkowany jest na kraje członkowskie niż na kraje trzecie. Różnice pomiędzy ugrupowaniami dotyczą zmian tego ukierunkowania. Specjalizacja kierunkowa umacniała się w przypadku CACM i CAN, pozostawała bez zmian dla krajów EAC, a zmniejszyła się dla MERCOSUR

International food aid – directions of changes

Permanently unsolved world food insecurity problem makes the international community search for solutions. One of the used methods is international food aid directed to developing countries. Long term analyses of the food aid flows allow to identify some tendencies that show: increase of emergency food aid and decrease of direct transfer. These tendencies also apply to the two biggest food donors i.e. the USA and the EU. The noticeable directions of changes are based on the international community initiatives, on which the national regulation are formed later

Pomoc żywnościowa w kontekście good governance i społecznej odpowiedzialności

The paper focuses on the issue of food aid as a kind of implementation of good governance and social responsibility of rich countries towards poor countries. The study may be characterized as a review. In the first part, hunger as a global problem of the modern world economy is taken under consideration. In the second part, the food aid is characterized by taking into account the form of food delivery, methods of food purchase, main donators and beneficiaries. The author concludes by emphasizing that food aid due to the unsolved problem of hunger has been steadily decreasing, it is determined by political and economic factors, and its ultimate impact on the food situation in developing countries is not clear. / Synopsis. W pracy zwrócono uwagę na kwestię pomocy żywnościowej jako swego rodzaju sposób realizacji „good governance” i społecznej odpowiedzialności krajów bogatych względem krajów biednych. Opracowanie ma charakter przeglądowy. W pierwszej części przedstawiono niedożywienie jako problem globalny współczesnej gospodarki światowej. W drugiej części scharakteryzowano pomoc żywnościową z uwagi na formę jej dostarczania, sposób zakupu, czy głównych dostawców i odbiorców. W podsumowaniu podkreślono, że pomoc żywnościowa w warunkach nierozwiązanego problemu głodu systematycznie maleje, jej udzielanie jest determinowane czynnikami politycznymi i ekonomicznym, a jej ostateczny wpływ na sytuację żywnościową w krajach rozwijających się nie jest jednoznaczny