Type 1 diabetes mellitus (T1DM) is the most severe form of diabetes, which is characterized by absolute insulin deficiency induced by the destruction of pancreatic beta cells. The aim of this study was to evaluate the effect of a structural analogue of apelin-12 ((NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, metilin) on hyperglycemia, mitochondrial (MCh) respiration in permeabilized cardiac left ventricular (LV) fibers, the myocardial energy state, and cardiomyocyte membranes damage in a model of streptozotocin (STZ) diabetes in rats. Metilin was prepared by solid-phase synthesis using the Fmoc strategy and purified using HPLC.
View Article and Find Full Text PDFCellulose was produced by the modified traditional method with 35% yield from the stem of Sosnovsky hogweed and was characterized by elemental analysis, infrared (IR) spectroscopy, powder X-ray diffractometry, differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS). For , the degree of crystallinity (approximately 70%) and the glass transition temperature (105-108 °C) were determined. It was found that the whiteness characteristic in the case of was 92% and this significate was obtained without a bleaching procedure using chlorine-containing reagents.
View Article and Find Full Text PDFAntioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.
View Article and Find Full Text PDFNeuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in experimental cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to elucidate the effect of WTLNSAGYLLGPβAH-OH (peptide G), a pharmacological agonist of the galanin receptor GalR2, on the cardiac injury induced by administration of streptozotocin (STZ) in rats. Peptide G was prepared by solid phase peptide synthesis using the Fmoc strategy and purified by preparative HPLC; its structure was confirmed by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry.
View Article and Find Full Text PDFThe design of new drugs for treatment of cardiovascular diseases based on endogenous peptide hormones is of undoubted interest and stimulates intensive experimental research. One of the approaches for development in this area is synthesis of the short bioactive peptides that mimic effects of the larger peptide molecules and have improved physicochemical characteristics. In recent years, it has been found that the N-terminal fragments of the neuropeptide galanin reduce metabolic and functional disorders in the experimental heart damage.
View Article and Find Full Text PDFAntioxidant properties of rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2 (Gal), N-terminal fragment of galanin (2-15 aa) WTLNSAGYLLGPHA (G1), and its modified analogue WTLNSAGYLLGPβAH (G2) were studied in vivo in the rat model of regional myocardial ischemia and reperfusion and in vitro in the process of Cu2+-induced free radical oxidation of human blood plasma low-density lipoproteins. Intravenous administration of G1, G2, and Gal to rats after ischemia induction reduced the infarction size and activities of the necrosis markers, creatine kinase-MB and lactate dehydrogenase, in blood plasma at the end of reperfusion. G1, G2, and Gal reduced formation of the spin adducts of hydroxyl radicals in the interstitium of the area at risk during reperfusion, moreover, G2 and Gal also reduced formation of the secondary products of lipid peroxidation in the reperfused myocardium.
View Article and Find Full Text PDFThe use of the anticancer drug doxorubicin (Dox) is limited by its cardiotoxic effect. The aim of this work was to study the effect of a new synthetic agonist of the galanin receptor GalR1-3 [βAla14, His15]-galanine (2-15) (G) on the metabolism, antioxidant enzyme activity, and cardiac function in rats with cardiomyopathy (CM) caused by chronic administration of Dox. Coadministration of peptide G and Dox significantly increased the fractional shortening (FS) and ejection fraction (EF) by an average of 30 ± 4% compared with the indices in the Dox group.
View Article and Find Full Text PDFChemically modified peptide apelin-12 ([MeArg, NLe]-apelin12, peptide M) is able to reduce reactive oxygen species (ROS) formation, cell death, and metabolic and ionic homeostasis disorders in experimental myocardial ischemia-reperfusion injury. These beneficial effects indicate the therapeutic potential of this compound in cardiovascular diseases. The goals of this work were to optimize the synthesis of peptide M, and to study its proteolytic stability and effect on the heart function of rabbits with doxorubicin (Dox) cardiomyopathy.
View Article and Find Full Text PDFThe mechanisms of protective action of the neuropeptide galanin and its N-terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]-galanin (2-15) (G1) and the full-length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology.
View Article and Find Full Text PDFThe goal of this study was to examine effects of a novel galanin receptor agonist GalR1-3 [bAla14, His15]-galanine 2-15 (G), obtained by automatic solid-phase synthesis, on the metabolic state of the area at risk and the size of acute myocardial infarction (MI) in rats in vivo and evaluate its toxicity in BALB /c mice. In anesthetized rats, regional ischemia was simulated by coronary artery occlusion and then coronary blood flow was restored. The peptide G was administered intravenously (i.
View Article and Find Full Text PDFThe use of the anticancer drug doxorubicin (Dox) is limited due to its cardiotoxic effect. Using the method of automatic solid-phase peptide synthesis, we obtained a synthetic agonist of galanin receptors GalR1-3 [RAla14, His15]-galanine (2-15) (G), exhibiting cardioprotective properties. It was purified by high performance liquid chromatography (HPLC).
View Article and Find Full Text PDFN-terminal fragments of galanin (2-11) and (2-15) are critical for binding to GalR1-3 receptors, members of the G-protein-coupled receptor superfamily, and are involved in myocardial protection against ischemia/reperfusion (I/R) injury. This study was designed to synthesize novel GalR1-3 agonists with improved properties and evaluate their efficiency as cardioprotective agents. Peptide agonists were synthesized by the automatic solid phase method using Fmoc technology and purified by preparative HPLC.
View Article and Find Full Text PDFThe clinical use of antineoplastic agent doxorubicin (DOX) is limited due to its cardiotoxic action. [βAla14, His15]-galanine (2-15) (G) is a novel synthetic agonist of galanin receptors GalR1-3 having cardioprotective properties in animal models in vivo. The aim of the present study was to explore effects of G on DOX-induced cardiotoxicity.
View Article and Find Full Text PDFAim: To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin.
Materials And Methods: Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination.
Zh Nevrol Psikhiatr Im S S Korsakova
May 2019
Aim: The aim of the research was to study the dynamics of neurologic disorders in the context of combined therapy in patients with type 2 diabetes mellitus.
Material And Methods: We examined 50 patients with diabetic polyneuropathy aged 50-70 years, with more than 12 months disease duration. The main group (n=30) included the patients who received 18 injections of Cocarnit against the background of hypoglycemic therapy.
Agonists and antagonists for galanin receptor subtypes GalR1-3 can be used as putative therapeutics targets for the treatment of various human diseases. However, effects of galanin and its N-terminal fragments on myocardial ischemia/reperfusion injury remain unclear. This study was designed to assess the ability of the full-length galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G1), the natural fragments WTLNSAGYLL-NH2 (G2) and WTLNSAGYLLGPHA (G3), and their modified analogs WTLNAAGYLL (G4) and WTLNSAGYLLGPβAH (G5) to limit acute myocardial infarction in rats in vivo.
View Article and Find Full Text PDFThe maintenance of nitric oxide (NO) bioavailability has been recognized as an important component of myocardial protection during cardiac surgery. This study was designed to evaluate the efficacy of using two NO-donating compounds in cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working rat hearts were subjected to normothermic global ischemia and reperfusion.
View Article and Find Full Text PDFIn our study urine protein composition of 18 healthy volunteers was compared with that of 18 patients with ischemic heart disease and concomitant hypertension. Liquid chromatography-mass-spectrometry (LC-MS) analysis of the second fraction of morning urine was carried out using nano-line high performance liquid chromatograph and hybrid mass spectrometer. The analysis revealed 23 proteins expressed in the endothelium, according to the information contained in the database Bgee, and 49 proteins, with direct functional link with the processes in the endothelium in the reconstruction of associative networks using ANDSystem program.
View Article and Find Full Text PDFBackground And Purpose: Galanin is an endogenous peptide involved in diverse physiological functions in the central nervous system including central cardiovascular regulation. The present study was designed to evaluate the potential effects of the short N-terminal galanin fragment 2-15 (G) on cardiac ischemia/reperfusion (I/R) injury.
Experimental Approach: Peptide G was synthesized by the automatic solid phase method and identified by 1H-NMR spectroscopy and mass spectrometry.
Background And Purpose: Galanin is a multifunctional neuropeptide with pleiotropic roles. The present study was designed to evaluate the potential effects of galanin (2-11) (G1) on functional and metabolic abnormalities in response to myocardial ischemia-reperfusion (I/R) injury.
Experimental Approach: Peptide G1 was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase method.
An alkyl azide derivative of 1-phenylethynylpyrene (PEPy) dye was prepared and used in the functionalization of oligonucleotides via click chemistry. Spectral and photo-physical properties of the PEPy-modified oligonucleotides as a single strand, and in perfect or mismatched duplexes, have been studied. A series of PEPy-Dabcyl fluorogenic TaqMan probes were synthesized and tested in qPCR.
View Article and Find Full Text PDFThe study was carried out to establish values of parameters characterizing concentrations of pathogens (threshold cycle - Ct) correlating with acute phase of viral gastroenteritis. The groups of patients with sporadic and group morbidity of acute intestinal infections were examined. The reagents kits Amplience (The central research institute of epidemiology, Russia), in real-time format polymerase chain reaction were applied to detect Rotavirus grA, Norovirus GII, Astrovirus, Adenovirus grF, Shigella spp, EIEC, Salmonella spp, Campylobacter spp (thermophilic group).
View Article and Find Full Text PDFThe study was carried out to evaluate and compare analytical characteristics of reagents kits for identification of antigens of rotaviruses SD BIOLINE Rotavirus (Standard Diagnostics, Korea), RIDA Quick Rotavirus (R-biopharm AG, Germany), RotaStick One-Step Test (Novamed Ltd., Israel), QuickStripe Rotavirus (Savyon doagnostics Ltd., Israel), Rotavirus-antigen-IFA-BEST (Vector-Best, the Russian Federation), Rota-antigen (NPP AKVAPAST, the Russian Federation).
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