Biomedical subjects

W Kowalczyk

Publications and source records attributed to W Kowalczyk.

15 recordsLinked to original sources

PubMed2005

Analogues of arginine vasopressin and its agonist and antagonist modified in the N-terminal part of the molecule with l-beta-homophenylalanine.

In continuation of our efforts to elucidate the role of positions 2 and 3 in arginine vasopressin (AVP) and its analogues, we designed and synthesized peptides modified in these positions with l-beta-homophenylalanine (beta-Hph). Two of them had just this single modification, the next two peptides are analogues of the V2 agonist, namely [3-mercaptopropionic acid (Mpa)1]AVP (dAVP). The last two compounds were designed by substitution of positions 2 or 3 of a potent V(1a) antagonist, [1-mercaptocyclohexaneacetic acid (Cpa)1]AVP, with beta-Hph. All the peptides were tested for their pressor and antidiuretic and uterotonic in vitro activities in the rat. All the activities tested have been found to be significantly decreased. Three analogues, i.e. [Mpa(1),beta-Hph2]AVP, [Cpa1,beta-Hph2]AVP, [Cpa1,beta-Hph3]AVP, turned out to be uterotonic antagonists with pA2 = 6.3 +/- 0.2, 6.3 +/- 0.1, 6.0 +/- 0.3 respectively. The last one exhibited antipressor properties also (pA2 = 6.4 +/- 0.1).

Aminobutyrates↗

PubMed2004

Potent bradykinin antagonists containing N-benzylglycine or N-benzyl-l-alanine in position 8.

Two new analogues of a previously designed bradykinin (BK) antagonist, d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Phe-Thi-Arg, substituted in position 8 by N-benzylglycine and N-benzyl-l-alanine were designed, synthesized and bioassayed. The results show an impressive enhancement of B2 antagonistic potencies of both peptides in comparison with the model. In two further analogues these modifications were combined with acylation of the N-terminus with 1-adamantanacarboxylic acid. Acylated analogues exhibited higher antagonistic potency in comparison with the parent compounds, however, the range of effect was not as high as in previously described cases. The activity of analogues was assessed by their ability to inhibit vasodepressor response to exogenous BK (rat blood pressure test). Our results may be of value in the design of more potent BK antagonists.

Alanine↗

PubMed2004

Cis/trans conformational equilibrium across the N-methylphenylalanine- N-methylphenylalanine peptide bond of arginine vasopressin analogs.

Two cyclic analogs of vasopressin, -Pro-Arg-Gly-NH(2) (1) and -Pro-Arg-Gly-NH(2) (2) were synthesized by the solid phase method. Their structure was determined in aqueous solution by two-dimensional NMR techniques and simulated annealing algorithm from an extended template in X-PLOR. The total chemical shift correlation spectroscopy and rotating-frame Overhauser enhancement spectroscopy of the peptides displayed four distinct sets of residual proton resonances. This suggests that both analogs adopt four families of conformations in H(2)O/D(2)O (9 : 1) (one major and three minor species). In further analysis only signals of major species (M) and of one minor species (m(1)) were considered. The major species of both peptides include a trans peptide bond between the first and second residue, and a cis form between the second and third residue. In the minor species, all peptide bonds were found to exist in trans geometry.

Arginine Vasopressin↗

PubMed2004

Analogues of arginine vasopressin modified in the N-terminal part of the molecule with enantiomers of N-methylphenylalanine.

Four new analogues of arginine vasopressin (AVP) substituted in positions 2 and 3 with all possible combinations of enantiomers of N-methylphenylalanine were synthesized and studied to assess the influence of N-methylation of the peptide bonds between the first three amino acids on the pharmacological properties of the resulting peptides. The next three analogues were designed to learn how the shortening of the peptide chain, by removal of one of the N-methylphenylalanine residues, would affect pharmacological properties of the resulting compounds. The activity of the analogues was tested in the in vitro uterotonic, pressor and antidiuretic tests. None of the prepared analogues displayed significant biological activity with the exception of [Me-d-Phe(2), Me-Phe(3)]AVP and [Me-d-Phe(2,3)]AVP, which showed low antiuterotonic activity (pA(2) = 6.6 and pA(2) = 6.4, respectively). Our results, while not impressive in terms of biological activity, may be helpful for designing potent and selective oxytocin antagonists.

Animals↗

PubMed2003

Influence of 1-aminocyclohexane-1-carboxylic acid in position 2 or 3 of AVP and its analogues on their pharmacological properties.

In this study we describe the synthesis and some pharmacological properties of seven new analogues of arginine vasopressin (AVP) substituted in position 2 or 3 with 1-aminocyclohexane-1-carboxylic acid (Acc). All peptides were tested for the pressor, antidiuretic and uterotonic in vitro activities. The Acc3 modifications of AVP, dAVP, [d-Arg8]VP and [Cpa1]AVP have been found to be deleterious for interaction with all three neurohypophyseal hormone receptors, as judged from the several orders of magnitude decreased biological activities, whereas Acc2 substitution selectively altered the interaction with the receptors. Two of the new analogues, [Acc2]AVP and [Acc2, d-Arg8]AVP, are potent antidiuretic agonists. [Acc2]AVP exhibits moderate pressor agonistic activity and weak antiuterotonic properties. [Acc2, d-Arg8]AVP has been found to be a weak antagonist in the pressor and uterotonic tests. Another analogue - [Cpa1, Acc3]AVP - turned out to be a highly selective V2 agonist. This is an unexpected effect, as its parent peptide, [Cpa1]AVP is a very potent V1a receptor antagonist. This is the first Cpa1 modification to have resulted in V2 agonism enhancement. Besides providing useful information about structure-activity relationships, our results could open up new possibilities in the design of highly potent and selective V2 agonists.

Amino Acids, Cyclic↗

PubMed1993

Phosphorylation of acidic ribosomal proteins by ribosome-associated protein kinases of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

Two proteins of 13 kDa and 38 kDa, the components of 60S ribosomal subunits, were identified as phosphorylation substrates for protein kinases tightly associated with S. cerevisiae and Schizosaccharomyces pombe ribosomes. An enzyme with properties of multifunctional casein kinase II was detected in ribosome preparations from both yeast species. In S. cerevisiae another protein kinase with high substrate specificity toward those proteins was also identified. By using isoelectric focusing, the protein band of 13 kDa from S. cerevisiae and S. pombe was resolved respectively into three and four major forms of different charge. The same protein forms were phosphorylated in the in vivo 32P-labelling experiments.

Amino Acid Sequence↗

PubMed1991

Changes in brain bioelectrical activity (EEG) after repetitive exposure to an organo-phosphate anticholinesterase. II. Rat.

Effects of repetitive exposure (ten times in a period of two weeks) to chlorphenvinphos (CVP), at daily doses of 0.5 and 1.0 mg/kg, i.p., were studied in adult male Wistar rats of imp-DaK stock. It was found that 3 hrs after the last exposure, the cholinesterase (ChE) activity in the blood and brain was close to 50% of the control value in the 0.5 mg/kg group and less than 50% in the 1.0 mg/kg group. In both groups, normalization of ChE activity in plasma took less time than in erythrocytes, and the normalization of ChE activity in erythrocytes proceeded faster than in the majority of the brain areas studied. Electrophysiological investigations revealed a retardation of age-related epileptic-like cortical activity. This effect, however, was present only in the 1.0 mg/kg group, and only in the period of decreased ChE activity in the brain. Spectral analysis revealed an increase in 1-4 Hz activity in the cortical EEG of the 0.5 mg/kg group and heightened theta activity (4-7 and 7-9 Hz bands) in the hippocampal EEG of the 1.0 mg/kg group. The later effects were detected after a time sufficient for full normalization of ChE activity and manifested themselves most clearly in the presence of an acoustic stimulus associated with pain. The above results are in agreement with earlier observations on rabbits exposed repetitively to CVP. Data from both species suggest that, in the case of repetitive exposure to CVP, neither plasma nor erythrocyte ChE activity is a reliable indicator of toxicity, and that such exposure to this OP may lead to changes in EEG outlasting the period of lowered ChE activity in the blood and brain.

Animals↗

PubMed1991

Sensitivity of the replica method in the detection of candidal infection among denture wearers with clinically healthy oral mucosa.

To ascertain the role of Candida in denture stomatitis, the practitioner must conduct a mycologic examination of the acrylic resin denture surface, because it acts as a reservoir for continuous reinfection of the palate. Twenty-two patients were examined to compare the sensitivity of the standard technique of swabbing the denture to that of a newly developed cast agar replica technique for detecting Candida albicans. The dentures were swabbed and cast replicas of the tissue-fitting surface of the dentures were made of both study populations. The majority of cultures obtained by swabbing failed to detect the presence of Candida albicans, while all cast agar replicas grew Candida albicans. The replica method for the detection of Candida albicans in edentulous patients seemed to be a more sensitive method than currently available mycologic methods.

Aged↗

PubMed1990

Brain electrical activity (EEG) after repetitive exposure to chlorphenvinphos an organophosphate anticholinesterase: I. Rabbit.

Cholinesterase (ChE) activity in blood and brain as well as the hippocampal and cortical EEG were investigated in rabbits exposed once a day for a period of two weeks to an organophosphate insecticide, chlorphenvinphos (CVP). The daily dose of CVP was 14.0 mg/kg i.p. ChE activity in plasma and erythrocytes decreased by 60 and 48%, respectively, by the end of exposure and returned to the preexposure level within 35 days. In the exposed animals, killed and dissected a day after, the ChE activity in blood had been found normal, the level of ChE activity in some parts of the brain was still significantly depressed. The spontaneous hippocampal EEG showed no changes as soon as 24 hours after the exposure. However, after a period sufficiently long for the normalization of ChE activity in blood, the hippocampal arousal response (theta rhythm) to click and to a tone associated with pain was found heightened in the exposed rabbits. Moreover, spectral analysis of 5 minute EEG samples revealed a decrease in the content of 7-13 Hz activity in the cortex of the exposed animals as compared to the control ones. The obtained data suggest that exposure to CVP may lead to functional changes in the brain outlasting the period of ChE depression.

Animals↗

PubMed1989

Changes in physiological and electrophysiological parameters in rabbits after single exposure to chlorphenvinphos.

In order to evaluate some of the central effects of an organophosphorus pesticide--chlorphenvinphos (CVP), the time course of changes in the activity of blood cholinesterase (ChE), body temperature and hippocampal EEG were compared in rabbits after acute i.p. exposure. The pesticide was administered twice at an interval of 80-90 days. The Deichmann-LeBlanc scheme of dosing (one animal/one dose) was adopted starting with 22 mg/kg. CVP resulted in a dose-dependent decrease in plasma and erythrocyte ChE activity, a decrease in body temperature ranging from 0.7 degrees to 3.5 degrees C, and in an increase in content of the immobility-related, rhythmic slow activity (I-RSA) in the hippocampal EEG. Changes in body temperature appeared at lower doses than those in the hippocampal EEG. Contrary to the changes in ChE activity, which lasted 4-30 days, those in body temperature and in hippocampal EEG disappeared within 24 hours after the injection. CVP administered at the same dose 80-90 days after the first injection, resulted again in an inhibition of ChE activity, but the effect on the hippocampal EEG was less clear, and that on body temperature was variable; no effect, an increase or a decrease appeared. The data suggest that: i) body temperature is a more sensitive index of a central action of CVP administered for the first time than the hippocampal EEG; ii) the brain cholinergic mechanisms are relatively resistant to the acute action of the OP and undergo fast adaptive changes; iii) even single exposure to CVP may produce some long-lasting functional changes in the brain of some subjects, which has been proven by the changed response to the second exposure.

Animals↗

PubMed1974