Wyniki wyszukiwania - Biblioteka Nauki

1

Modyfikowane oligodeoksyrybonukleotydy zawierające w wiązaniu internukleotydowym w pozycji mostkowej atom azotu

100%

Radzikowska E.

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tom [Z] 67, 11-12

1003--1025

EN

Synthetic oligonucleotides (ONs) constitute an important class of compounds which exhibit biological activity. As potential drugs ONs are employed in the antisense strategy [1]. The antisense therapeutic agent acts on the pathogenic mRNA causing inactivation of the target. Ideal antisense agent should be resistant to exo and/or endonucleases, have a suitable pharmacological and pharmacokinetic profile and high affinity for the target. To improve some properties of antisense oligonucleotides plethora of chemical modifications introduced within both sugar unit and internucleotides linkage were investigated. Among numerous ONs modified in internucleotide phosphodiester bond, one of the most interesting are oligonucleotide phosphoramidates (NP-oligos) in which one of the bridging oxygens is replaced by nitrogen atom (at 3’ or 5’ position). Hence, two classes of compounds are formed: oligonucleotide-(N5’→P3’)phosphoramidates and oligonucleotide(N3’→P5’)-phosphoramidates. These compounds, similar to native DNA and RNA, possess an achiral phosphorous atom and all internucleotides bonds are negatively charged. Additionally, NP-oligo shows good resistance to nucleolytic degradation and can bind to the target DNA or RNA with high affinity [12]. In literature several synthetic strategies concerning both (N5’→P3’) and (N3’→P5’) NP-oligos have been described. Some of them allowed to obtain only corresponding dimers. In the light of recent discoveries the most promising candidates for therapeutic and diagnostic applications are oligonucleotide-(N3’→P5’)thiophosphoramidates. Gryaznov et al. have found that such compounds can act as potent and selective telomerase inhibitors [29]. Human telomerase (TA) is a reverse transcriptase ribonucleoprotein that synthesizes de novo d-(TTAGGG)n repeats at chromosomal DNA ends. Whereas activity of this enzyme is observed in ~85% of all human tumors, most of normal somatic cells either lack TA activity or express it only at low levels. For these reasons TA constitute an attractive and nearly universal anticancer target for rational drug development.

2

Rak pluca. Tkankowo-specyficzne oddzialywania miedzy genami supresorowymi, onkogenami oraz genami warunkujacymi genetyczna podatnosc na nowotwor.

63%

Pawlak A. L. , Radzikowska E.

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tom 10

329-342

3

Variational principle in thermo-electro-magneto-dynamics of micropolar media

63%

Kotowski R. , Radzikowska E.

Journal of Technical Physics

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1998

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tom Vol. 39, no 2

283-295

EN

The variational principle for micropolar continua interacting with thermal, electromagnetic and mechanical fields is formulated. The potential character of the electromagnetic fields (E, B) and the conservation of electric charge, mass and microinertia are postulated. The remaining equations and the boundary conditions are obtained from the variational principle. The expression for the entropy production is obtained too. We conclude that the proposed variational principle describes both the thermodinamically reversible and dissipative processes.

4

Koniugaty peptyd-oligonukleotyd : synteza i zastosowanie

51%

Kaczmarek R. , Radzikowska E. , Baraniak J.

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tom [Z] 62, 11-12

1091-1113

EN

Recently major advances have been made in the development of oligonucleotides as potential therapeutic agents [1-3]. However, a frequent limitation of their use is poor cellular uptake [5]. Among the many molecules that have been reported to enhance cell delivery of oligonucleotides there is a number of peptide carriers. They are preferably linked by covalent bond in many possible ways, resulting in a new class of compounds known as peptide-oligonucleotide conjugates (POCs) [6a, 9]. A variety of chemical linkages have been used to link the peptide and oligonucleotide fragments. A peptide can be conjugated either at the base-, 3'-, or 5'-position of the sugar unit or at the backbone of the oligonucleotide [10]. Similarly, the point of conjugation in a peptide can be either the C- or N-terminus or the side chain. Two different strategies have been adopted for the synthesis of POCs: in-line solid-phase synthesis (divergent method) and fragment conjugation (convergent method) [11]. In divergent method, the peptide and oligonucleotide fragments are assembled on automatic synthesizers, sequentially on the same solid support, until the final step. In predominant cases, the peptides are assembled first by the Fmoc method, while the oligonucleotides are assembled next using the phosphoramidite method [12]. In-line synthesis could be most direct for preparing POCs, but finding the right combination of protecting groups is the key problem. The first step in preparation of POCs involves modification of solid supports with suitable linkers [10]. A number of monofunctionalized as well as bifunctionalized linkers were immobilized over solid supports through suitable spacers (Figure 1). In the fragment conjugation, the peptide and oligonucleotide fragments are synthesized individually, cleaved from their solid supports, deprotected and purified, separately. Therefore, the most appropriate synthetic chemistry can be used for each component without concern for incompatibility. Both biopolimers are finally linked postsynthetically utilizing the reactive functional groups which are attached at the desired site of conjugation (Figure 4) [5]. If the postsynthetic conjugation is performed with one of the oligomers still joined to the solid phase, it is called the solid-phase fragment conjugation method. Alternatively, if the conjugation is effected after complete isolation and purification of the peptides and oligonucleotides, it is called fragment conjugation in the liquid phase [10]. Besides their potential use for therapeutic applications, POCs can serve as research tools, for example, as fluorescent probes [44] or PCR primers [25, 45]. With increased specificity and strength of target binding, POCs may be useful in diagnostic applications or as affinity purification reagents.

5

Synteza modyfikowanych oligonukleotydów zawierających stereozdefiniowane internukleotydowe wiązania tiofosforanowe

51%

Radzikowska E. , Kaczmarek R. , Baraniak J.

Wiadomości Chemiczne

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2015

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tom [Z] 69, 11-12

957--981

EN

Synthetic oligonucleotides constitute an important class of compounds which can exhibit biological activity. As potential drugs they could be employed in antisense strategy by acting on the pathogenic mRNA, causing inactivation of the target molecules during the translation process [1]. Ideal antisense agent (ASO) should be resistant to exo and/or endonucleases, exhibit a suitable pharmacological and pharmacokinetic profile and exhibits high binding affinity towards the target mRNA. To improve some properties of the ASO plethora of the chemical modifications introduced within the nucleobase, sugar unit and internucleotide linkage are investigated [3]. Among them, phosphorothioate oligonucleotides (PS-oligo), created by replacing one of the nonbridging oxygen atoms with a sulfur atom, are the major representatives of DNA analogs. PS-oligo display several attractive features like nuclease resistance, activation of RNase H, and good pharmacokinetic properties [1]. Replacement of one of two nonbridging oxygens at phosphorus by sulfur induces asymmetry at the phosphorus atom. Hence, the synthesized oligo(nucleoside phosphorothioate) is a mixture of 2n diastereomers (where n is the number of internucleotide phosphorothioate functions). Therefore the actual biological activity of the P-chiral oligonucleotide analogues, (e.g., interactions with proteins or nucleic acids) may depend on stereochemical factors [7]. One has to keep in mind that the phosphoramidite [5] and H-phosphonate [32] methodologies (commonly used to prepare PS-oligo) are nonstereospecific and give a mixture of 2n diastereomers. Thus, various methods have been elaborated to synthesize these P-chiral oligonucleotide analogs in a stereocontrolled manner [15, 17], among them the oxathiaphospholane method developed by Stec et al. [18], the method utilizing nucleoside 3’-O-(3-N-acyl)oxazaphospholidine derivatives as monomer units [19], and the method based on a stereoselective synthesis of nucleoside 3’-O-oxazaphospholidine monomers [21, 22] are the most significant.

6

Diagnostic difficulties in the differentiation of urine retention and developmental anomalies in the pelvicalyceal system in the ultrasound examination of children

51%

Wieczorkiewicz-Plaza A. , Zajaczkowska M. , Radzikowska E. , Maciejewski R.

Folia Morphologica

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2004

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tom 63

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nr 2

EN

Ultrasound examination of the abdominal cavity is part of the baseline diagnostics of urinary tract diseases. Dilatation of the pelvicalyceal system is one of the most frequent findings. In ultrasonography of the urinary tract there are, however, some images of anatomical anomalies of the pelvicalyceal system which should not be consider as abnormal. In the study we analysed 920 ultrasound examinations of the urinary tract. Of all the ultrasound images only those with isolated dilatation of the renal pelvises and calices were selected (130 cases). Ampulla-shaped and/or external pelvises, isolated calices or both abnormalities were disclosed in 104, 46 and 20 cases, respectively. In about one-third of patients additional examinations (voiding cystography, intravenous urography, renal scyntygraphy) were performed which revealed normal anatomy of the urinary tract and disorders of urine flow in 80% and 20% of patients, respectively. In conclusion, the study implies that not all dilatation of the pelvicalyceal system structures signifies urine retention, although in the event of further doubt, there is a need for additional diagnostics.

7

The effects of short-time caffeine administration on skeleton development in Wistar rats

45%

Burdan F. , Madej B. , Wojtowicz Z. , Maciejewski R. , Radzikowska E.

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nr 2

8

Rola wybranych parametrów biochemicznych w przewidywaniu zmian histopatologicznych w 24. i 48. godzinie od wystąpienia ostrego zapalenia trzustki

38%

Baj J. , Luszczewska-Sierakowska I. , Radzikowska E. , Sompor J. , Maciejewski M. , Dabrowski A.

Medycyna Weterynaryjna

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2019

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tom 75

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nr 01

EN

The aim of the study was to assess the relationships between the degree of changes in concentrations of the biochemical indicators in serum such as: creatinine, uric acid, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), lipase, amylase, glucose, iron and magnesium, and histopathological lesions occurring in the pancreas within 24 and 48 hours from the induction of acute pancreatitis (AP). An attempt was made to assess the relation between the changes in concentrations of biochemical indicators and the enhancement of histological lesions in the pancreas based on Spormann score. In the experimental model, the laboratory and histological changes in the 24th hour from administration of taurocholan correspond to the seventh day of the disease in humans. Experiments were conducted on 55 male Wistar rats weighing from 250 g to 300 g. The animals were divided into three groups: Z – a group serving to establish the ranges of studied factors and histological structure; K – a group of animals operated on which were injected with 0.9% NaCl into the biliary-pancreatic duct; E – a group of animals operated on in which acute pancreatitis was induced by an injection of 5% sodium taurocholate into the biliary-pancreatic duct. The material for biochemical and histological examinations was collected after 24 and 48 hours from the induction of AP. Whole pancreases were dissected for histological examinations and the samples were dyed with hematoxylin and saturated alcoholic eosin solution. The degree of pancreatic lesions was assessed according to the Spormann score. Quantitative variables were characterised by arithmetic mean, standard deviation, median, minimum and maximum value and 95% CI. After administration of 0.9% NaCl in the K group, foci of purulent inflammation in the fatty tissue of the pancreas and minor foci of Balser’s necrosis appeared. In the E group, after injection of 5% sodium taurocholate into the biliary-pancreatic duct, more intense lesions were observed: foci of fatty tissue necrosis, hemorrhagic necrosis, multifocal fatty tissue necrosis and inflammatory infiltration. The model was developed in order to assess histological lesions, indicating the character of AP, taking into account edema, inflammatory infiltration, fatty tissue necrosis, glandular necrosis, and ecchymoses. In the period of 24 hours, statistically significant differences between the K group and E group were observed for creatinine, total bilirubin, ALT, lipase, amylase, iron and magnesium, while in the period of 48 hours, statistically significant differences were observed for total bilirubin and ALT. In the group E, in the period of 24 hours concentrations of creatinine, total bilirubin, ALT, lipase, amylase and magnesium were significantly higher than in the group K, but concentrations of iron were significantly lower. In the period of 48 hours, in the E group total bilirubin was significantly lower and ALT was significantly higher than in the K group. In the E group, the intensity of pancreatitis increased together with an increase in ALT concentration in the period of 24 hours; in the period of 48 hours, the intensity of pancreatitis increased together with a decrease in ALT in the E group. In the K group, in the period of 48 hours, intensity of fatty tissue necrosis increased together with a decrease in ALT level. In the period of 48 hours, in the E group intensity of glandular necrosis increased together with a decrease in total bilirubin and AST concentration. In the E group, in the period of 24 hours intensity of edema increased together with an increase in magnesium level. In the period of 48 hours, in the E group intensity of glandular necrosis increased together with a decrease in magnesium or AST level, and the intensity of lesions in the form of ecchymoses increased together with an increase in glucose level. Histopathological lesions occurred prior to changes in laboratory test results, whereas significant correlations with the Spormann score concerned changes in: total bilirubin, AST, ALT, glucose and magnesium. The use of regression analysis with the Spormann score shows statistically significant differences for most of the biochemical parameters in the period of 24 hours correspond to the seventh day of the disease in humans. The presented study results confirm the fact that diagnostics of acute pancreatitis is very difficult and requires monitoring of many laboratory parameters. A search is still going on for an ideal marker of AP which would enable an early prognosis of the progress of the disease and the confirmation of its etiology. A discovery of a simple marker which is cheap to use may turn out to be useful if it is confirmed in prospective studies. The current state of knowledge based on scientific and clinical findings makes it possible to apply interdisciplinary clinical procedures based on matching appropriate laboratory and radiological tests, and on implementing therapeutic procedures.

9

Evaluation of histopathological changes of the pancreatic tissue in the course of acute experimental pancreatitis

38%

Anasiewicz A. , Madej B. , Maciejewski R. , Miroslaw C. , Draus J. , Lakowska H. , Radzikowska E.

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nr 4

10

Changes of hydroxyproline levels in myocardium after chronic administration of bleomycin

38%

Anasiewicz A. , Wojcik K. , Abramowicz K. , Lakowska H. , Bentkowski M. , Przywra S. , Radzikowska E.

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nr 4

11

Modulatory effect of sera from sarcoidosis patients on mononuclear cell-induced angiogenesis

32%

Zielonka T. M. , Demkow U. , Bialas B. , Filewska M. , Zycinska K. , Radzikowska E. , Szopinski J. , Skopinska-Rozewska E.

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tom 58

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nr 5

12

Angiogenic activity of sera from patients with systemic autoimmune diseases in relation to clinical, radiological, and functional pulmonary status

32%

Zielonka T. M. , Demkow U. , Zycinska K. , Filewska M. , Korzeniewska M. , Radzikowska E. , Bialas-Chromiec B. , Kus J. , Wardyn K. A. , Skopinska-Rozewska E.

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2008

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tom 59

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nr 6

791-800