11 results on '"Irina Bobrova"'
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2. The sigma form of the second Painlevé hierarchy
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Irina Bobrova and Marta Mazzocco
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Algebra ,Nonlinear Sciences::Exactly Solvable and Integrable Systems ,Hierarchy (mathematics) ,Hamiltonian structure ,Operator (physics) ,Mathematics::Classical Analysis and ODEs ,General Physics and Astronomy ,Sigma ,Geometry and Topology ,Mathematical Physics ,Mathematics - Abstract
In this paper we study the so-called sigma form of the second Painleve hierarchy. To obtain this form, we use some properties of the Hamiltonian structure of the second Painleve hierarchy and of the Lenard operator.
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- 2021
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3. Cardioprotection of the enkephalin analog Eribis peptide 94 in a rat model of ischemia and reperfusion is highly dependent on dosing regimen and timing of administration
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Lars Grip, Björn Redfors, Niklas Bergh, Irina Bobrova, Yangzhen Shao, Lars O. Karlsson, Elias Spanos, and Elmir Omerovic
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Male ,Cardiotonic Agents ,Time Factors ,Enkephalin ,Myocardial Ischemia ,Ischemia ,Myocardial Reperfusion Injury ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Bolus (medicine) ,medicine ,Animals ,Dosing ,Evans Blue ,Pharmacology ,Cardioprotection ,Dose-Response Relationship, Drug ,Tetrazolium chloride ,business.industry ,Hemodynamics ,Enkephalins ,medicine.disease ,Rats ,chemistry ,Anesthesia ,business ,Reperfusion injury - Abstract
Eribis Peptide 94 (EP94) is an enkephalin analog with cardioprotective properties in ischemia and reperfusion. The aim of the present study was to define the optimal timing and dosing of the administration of EP94 during ischemia and reperfusion in a rat model. 172 anesthetized and mechanically ventilated male Sprague-Dawley rats were randomly assigned to different administration protocols of EP94 and subjected to 30 or 40 min of coronary artery occlusion followed by 2h of reperfusion. EP94 was administered intravenously at different doses and time intervals. Area at risk (AAR) and infarct size (IS) were determined by staining with Evans Blue (EB) and Triphenyl tetrazolium chloride (TTC), respectively. EP94 reduced IS/AAR when administered as a double bolus (0.5 µg/kg per dose), whereas single (1 μg/kg) or triple boluses (0.5 μg/kg per dose) did not confer any protection. Reduction of IS/AAR was of highest magnitude if EP94 was administered 5 and 0 min before the 30 min ischemic period (47% reduction, P
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- 2015
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4. Dose-dependent cardioprotection of enkephalin analogue Eribis peptide 94 and cardiac expression of opioid receptors in a porcine model of ischaemia and reperfusion
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Lars O. Karlsson, Levent M. Akyürek, Lizhen Li, Irina Bobrova, Niklas Bergh, Erik Bissessar, Garrett J. Gross, and Lars Grip
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Risk ,Cardiotonic Agents ,Enkephalin ,Swine ,medicine.drug_class ,Myocardial Infarction ,Myocardial Ischemia ,Ischemia ,Myocardial Reperfusion Injury ,Pharmacology ,Opioid receptor ,medicine ,Animals ,RNA, Messenger ,Receptor ,Cardioprotection ,Dose-Response Relationship, Drug ,business.industry ,Myocardium ,Hemodynamics ,Arrhythmias, Cardiac ,Enkephalins ,medicine.disease ,Disease Models, Animal ,Dose–response relationship ,Gene Expression Regulation ,Opioid ,Anesthesia ,Receptors, Opioid ,Female ,business ,Reperfusion injury ,medicine.drug - Abstract
Opioids confer cardioprotection after myocardial ischaemia and reperfusion. The primary aim of the present study was to evaluate the cardioprotective effect of different doses of enkephalin analogue Eribis peptide 94 (EP 94) in a porcine model of ischaemia and reperfusion. A secondary aim was to analyse the impact of ischaemia and reperfusion on the expression of opioid receptor subtypes in the porcine heart. Thirty-four anesthetised pigs underwent 40 min of balloon occlusion of the left anterior descending coronary artery followed by four hours of reperfusion. Pigs were given either vehicle (0.9% NaCl) or one of four doses of EP 94 (0.2, 1, 5 or 25 ug/kg at each administration, respectively), intravenously after 26, 33 and 40 min of ischaemia. Hearts were stained to quantify area at risk and infarct size. mRNA and protein expressions of the opioid receptor subtypes were detected with RT-PCR, immunoblotting and immunohistochemistry in the control and ischaemic/reperfused areas. There was a significant dose-response relationship between higher doses of EP 94 and reduced infarct size. Expression of κ- and δ-opioid receptors was detected at both mRNA and protein levels. In ischaemic/reperfused areas, an increased expression of mRNA for both receptors was observed, whereas only protein expression for the δ subtype was up-regulated. The μ-opioid receptor was not detected.
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- 2012
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5. Synthesis and biological activity of branched enkephalin analogues containing two amino acids in a side chain
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Guntis Rozental, Irina Bobrova, Anette Selander, Natalia Mishlakova, and Elena Mekshun
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Pharmacology ,chemistry.chemical_classification ,Enkephalin ,Chemistry ,Stereochemistry ,Organic Chemistry ,Biological activity ,Peptide ,General Medicine ,Ligand (biochemistry) ,Pentapeptide repeat ,Amino acid ,chemistry.chemical_compound ,Drug Discovery ,Peptide synthesis ,Side chain - Published
- 1998
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6. Synthesis and biological activity of branched enkephalin analogues
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Irina Bobrova, Natalia Mishlakova, Guntis Rozentals, Gunar Chipens, and Natalia Abissova
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Pharmacology ,chemistry.chemical_classification ,Enkephalin ,Stereochemistry ,Organic Chemistry ,Biological activity ,Peptide ,General Medicine ,Pentapeptide repeat ,Cyclic peptide ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Drug Discovery ,Peptide synthesis ,Asparagine ,Leucine - Abstract
The synthesis and biological activity of a new type of enkephalin analogs are reported. A series of branched pentapeptides of the enkephalin sequence with replacement of 2-glycine by D-ornithine and branching of the peptide chain in position 2 by attachment of proline, leucine, asparagine or methionine residues to the δ-amino group of D-ornithine were synthesized by classical solution methodology. Analgesic activity of the new analogs was assayed by the ‘tail pinch’ method following intracisternal and intravenous administrations to mice. They showed higher analgesic potency and longer duration of action as compared to linear and cyclic pentapeptides with the same amino acid composition. The activity determined in the GPI and MVD bioassays, and in a binding assay, revealed the preference of the branched analogs for the μ-type of opioid receptor over the δ-type. These results raise the possibility to synthesize enkephalin analogs with high analgesic potency and opiate receptor selectivity by varying the chemical character and length of the side chain in the 2-position.
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- 1998
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7. Acute and Chronic Cardioprotection by the Enkephalin Analogue, Eribis Peptide 94, is Mediated via Activation of Nitric Oxide Synthase and Adenosine Triphosphate-Regulated Potassium Channels
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Irina Bobrova, Kasem Nithipatikom, Erik Bissessar, Anna Hsu, Adam W. Pfeiffer, and Garrett J. Gross
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Male ,Cardiotonic Agents ,Enkephalin ,Ischemia ,Receptors, Opioid, mu ,Nitric Oxide Synthase Type II ,Myocardial Reperfusion Injury ,Pharmacology ,Nitric Oxide ,Article ,Nitric oxide ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,KATP Channels ,Receptors, Opioid, delta ,medicine ,Potassium Channel Blockers ,Animals ,Receptor ,Cardioprotection ,biology ,Chemistry ,Potassium channel blocker ,General Medicine ,Enkephalins ,medicine.disease ,Potassium channel ,Rats ,Nitric oxide synthase ,Benzamides ,biology.protein ,Nitric Oxide Synthase ,Hydroxy Acids ,Decanoic Acids ,medicine.drug - Abstract
Background/Aims: Eribis peptide 94 (EP 94) is a new enkephalin derivative which potently binds to the µ- and δ-opioid receptor. In this study, we determined the effects of EP 94 and potential mechanism(s) involved in cardioprotection of the rat heart. Methods and Results: An acute (5 and10 min into ischemia) and a chronic (24 h prior to ischemia) EP 94 administration produced a similar 30–40% reduction in infarct size/area at risk and the effects were blocked by the KATP channel antagonists, HMR 1098 and 5-HD. The cardioprotective effects were blocked by a nonselective nitric oxide synthase (NOS) inhibitor (L-NAME) following acute administration and by a selective iNOS inhibitor (1400W) following chronic administration. Conclusion: These results suggest that EP 94 may have potential for the treatment of ischemic heart disease via a nitric oxide (NO)-KATP-mediated mechanism.
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- 2012
8. Eribis peptide 94 reduces infarct size in rat hearts via activation of centrally located μ opioid receptors
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Anna Hsu, Erik Bissessar, Irina Bobrova, Garrett J. Gross, and Kasem Nithipatikom
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Male ,medicine.medical_specialty ,Cardiotonic Agents ,Enkephalin ,medicine.drug_class ,Narcotic Antagonists ,Myocardial Infarction ,Receptors, Opioid, mu ,Pharmacology ,Article ,Rats, Sprague-Dawley ,Opioid receptor ,Naltrindole ,Internal medicine ,medicine ,Animals ,Receptor ,Cardioprotection ,business.industry ,Antagonist ,Enkephalins ,Rats ,Endocrinology ,Opioid ,Blood-Brain Barrier ,Cardiology and Cardiovascular Medicine ,business ,Opioid antagonist ,medicine.drug - Abstract
Eribis peptide 94 (EP 94) is a novel enkephalin derivative that binds with high potency to μ and δ opioid receptors with less affinity for the κ opioid receptor. This compound has recently been shown to produce an acute reduction in myocardial infarct size in the anesthetized pig and rat partially via an endothelial nitric oxide synthase and KATP channel-dependent mechanism. EP 94 also was found to produce a chronic reduction in infarct size 24 hours postdrug administration via the upregulation of inducible nitric oxide synthase in rats. Despite these findings, no data have emerged in which the opioid receptor subtype responsible for cardioprotection has been identified and the site of action, heart, other peripheral organs, or the central nervous system, has not been addressed. In the current study, EP 94, was administered in 2 divided doses (0.5 μg/kg, intravenously) at 5 and 10 minutes into the ischemic period, and the opioid antagonists were administered 10 minutes before the onset of the 30-minute ischemic period. The selective antagonists used were the μ receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2), the δ receptor antagonists naltrindole and BNTX (7-benzylidenenaltrexone), and the κ receptor antagonist nor-BNI (norbinaltorphimine). Surprisingly, only CTOP completely blocked the cardioprotective effect of EP 94, whereas naltrindole, BNTX, and nor-BNI had modest but nonsignificant effects. Because there is controversial evidence suggesting that μ receptors may be absent in the adult rat myocardium, it was hypothesized that the protective effect of EP 94 may be mediated by an action outside the heart, perhaps in the central nervous system. To test this hypothesis, rats were pretreated with the nonselective opioid antagonist, naloxone hydrochloride, which penetrates the blood-brain barrier or naloxone methiodide, the quaternary salt of naloxone hydrochloride, which does not penetrate the blood-brain barrier before EP 94 administration. In support of a central nervous system site of action for EP 94, naloxone hydrochloride completely blocked its cardioprotective effect, whereas naloxone methiodide had no effect. These results suggest that EP 94 reduces infarct size (expressed as a percent of the area at risk) in the rat primarily via activation of central μ opioid receptors.
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- 2011
9. ChemInform Abstract: Synthesis and Biological Activity of Branched Enkephalin Analogues Containing Two Amino Acids in a Side Chain
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Anette Selander, Elena Mekshun, Irina Bobrova, Natalia Mishlakova, and Guntis Rozental
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chemistry.chemical_classification ,chemistry ,Enkephalin ,Stereochemistry ,Side chain ,Organic chemistry ,Biological activity ,General Medicine ,Amino acid - Published
- 2010
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10. Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine models for myocardial ischaemia and reperfusion
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Thomas Gustafsson, Jacob Odenstedt, Adrian T. Gonon, Irina Bobrova, Lars Grip, Erik Bissessar, Mohammad Kavianipour, Gerhard Wikström, and Lars O. Karlsson
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Agonist ,medicine.medical_specialty ,Cardiotonic Agents ,Enkephalin ,Nitric Oxide Synthase Type III ,medicine.drug_class ,Swine ,Ischemia ,Myocardial Infarction ,Myocardial Reperfusion Injury ,Gene Expression Regulation, Enzymologic ,Nitric oxide ,chemistry.chemical_compound ,Enos ,Internal medicine ,Medicine ,Animals ,Receptor ,Pharmacology ,biology ,business.industry ,Hemodynamics ,Enkephalins ,medicine.disease ,biology.organism_classification ,Disease Models, Animal ,chemistry ,Opioid Peptides ,Coronary occlusion ,Anesthesia ,Receptors, Opioid ,Cardiology ,Female ,business ,Reperfusion injury - Abstract
Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the μ- and δ-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect is associated with an increased expression of endothelial nitric oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40min of coronary occlusion followed by 4h of reperfusion. In Protocol I, balloon occlusion of the left anterior descending artery was performed with concurrent intravenous administration of (A) vehicle (n=7), (B) EP 94 (1ug/kg) after 5, 12, 19 and 26min of ischaemia (n=4) or (C) EP 94 (1ug/kg) after 26, 33, 40min of ischaemia (n=6). In Protocol II, open-chest pigs were administered (D) vehicle (n=6) or (E) 0.2ug/kg/min of EP 94 (n=6) through an intracoronary infusion into the jeopardized myocardium, started after 30min of ischaemia and maintained for 15min. The hearts were stained and the protein content of eNOS measured. EP 94 reduces infarct size when administered both early and late during ischaemia compared with vehicle (infarct size group A 61.6±2%, group B 50.2±3% and group C 49.2±2%, respectively, P0.05), as well as when infused intracoronary (infarct size group D 82.2±3.9% and group E 61.2±2.5% respectively, P0.01). Phosphorylated eNOS Ser(1177) in relation to total eNOS was significantly increased in the group administered EP 94, indicating activation of nitric oxide production.
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- 2010
11. A structure-activity study of nociceptin-(1-13)-peptide amide. Synthesis of analogues substituted in positions 0, 1, 3, 4 and 10
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Lubomir Kasakov, Mila Vlaskovska, Per Kårsnäs, Lars Terenius, Irina Bobrova, Natalija Egorova, Andrej Surovoy, and LarsErik Johansson
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Male ,Stereochemistry ,Peptide ,Pentafluorophenyl esters ,Ligands ,Nociceptin Receptor ,chemistry.chemical_compound ,Mice ,Radioligand Assay ,Structure-Activity Relationship ,Vas Deferens ,Drug Discovery ,Peptide synthesis ,Structure–activity relationship ,Animals ,Binding site ,Pharmacology ,chemistry.chemical_classification ,Binding Sites ,Ligand binding assay ,Organic Chemistry ,General Medicine ,Peptide Fragments ,Nociceptin receptor ,chemistry ,Amino Acid Substitution ,Opioid Peptides ,Receptors, Opioid - Abstract
A series of analogues of nociceptin, Noc(1-13)NH(2) (an agonist at the ORL1 receptor) was synthesized with following modifications: (1) N-terminal extension with Arg(0); (2) replacement of Gly(3) by basic or polar amino acids-Arg, Asn, Lys(For) or deletion; (3) exchange of Phe(1) or Phe(4) by Phe(NO(2)); (4) substitution of Ser(10) with D-Ser, Pro, D-Pro. The analogs were synthesized by solid-phase methodology using Fmoc-amino acid pentafluorophenyl esters. The affinity for the ORL1 and for the kappa, micro and delta-opioid receptors was investigated by radioligand binding assay and bioactivity by a mouse vas deferens (MVD) assay. The addition of the amino acid residue Arg to the N-terminal enhances the opioid receptor affinity of Noc(1-13)NH(2) while retaining ORL1 receptor affinity at a moderate level. The replacement of Gly in position 3 by the basic or polar amino acids-Arg, Asn, Lys(For) or its deletion led to inactive analogues. The replacement of Ser in position 10 by its D-isomer, Pro and D-Pro resulted in a series of analogues with the following order of activity: Ser(10)>D-Ser(10)>Pro(10)>D-Pro(10). In [D-Ser(10)]Noc(1-13)NH(2), introduction of an additional Phe(NO(2))(4) led to a >60-fold increase of ORL1 affinity, completely attenuating the loss of affinity brought about by Ser(10). In other analogues, introduction of Phe(NO(2))(4) did not change the magnitude of ORL1 binding significantly. Generally, while modifications in position 3 frequently led to a loss of most or all bioactivity, modifications in position 0 (Arg(0)) or 4 (Phe(NO(2))(4)) and 10 (D-Ser(10), Pro(10)) are tolerated.
- Published
- 2003
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