18 research outputs found
METABOLITHOTROPIC ASPECTS OF CARDIOPROTECTIVE ACTION OF NEW COMBINED MEDICINE BASED ON L-ARGININE AND THIOTRIAZOLIN AT MODELING OF MYOCARDIAL INFARCTION
Ă Ă Objectives: The actual problem of modern medicine is the development of medications in treatment of cardiovascular system diseases. Different combinations of L-arginine with thiotriazolin in acute myocardial ischemia were examined as part of study and the optimal combination has been established - 4:1, named Argitryl.ù⏠The aim is to study the antioxidant, energotropic, and nitric oxide (NO)-modulating mechanisms of the cardioprotective effects of L-arginine with thiotriazolin (4:1) (Argitryl) drug candidate compared to 4.2% solution for injections Tivortinù⏠(TOV Yuriya-Farm,ù⏠Ukraine) on the model of pituitrin-isadrin infarction of myocardium in laboratory rats.Methods: The study was conducted in accordance with Guidelines of State Expert Center of the Ministry of Health of Ukraine. All manipulations were carried out in accordance with the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.ù⏠The experiments were performed on 40 white outbred rats weighing 170ĂąâŹâ180 g. The antioxidant activity of the drugs was assessed by reduction of biochemical marker oxidative stress and an increase in the activity of the antioxidant system of the myocardium.Results: The study of energy metabolism has shown that the modeling of myocardial infarction leads to typical ischemic injuries - decrease in ATP, discoordination of the Krebs cycle, activation of anaerobic glycolysis in the cytosolic fraction of the heart of rats from the control group. Administration of Tivortin to animals does not lead to a significant decrease in ischemic injuries in the energy metabolism of the myocardium. The brightest anti-ischemic effect was observed with the appointment of Argitryl.ĂąâŹConclusion: The ascertained braking reaction of oxidative stress compared to the control group was found as a result of administration of Argitryl and Tivortin to animals with pituitrin-isadrin myocardial infarction. It was also found that the administration of Argitryl and Tivortin has a positive effect on the indices of the energy metabolism of the ischemic myocardium and leads to the normalization in conjugated NO system/renewed thiols. Argitryl significantly exceeds Tivortin on the influence of antioxidant, energy-tropic, and NO-modulating mechanisms of cardioprotective and anti-ischemic action on the studied indicatorsĂ
Functional nitric oxide conjugate systems state/restored heart thiols of rats in modeling isadrine-pituitrinâs myocardial infarction using metabolite-tropic cardioprotector âAngiolinâ
Background: According to modern researches, endothelial dysfunction (ED) is one of the primary pathogenetic elements of cardiovascular diseases (myocardial infarction [MI], ischemic heart diseases, cerebral ischemic stroke, atherosclerosis, arterial hypertension, pulmonary hypertension, heart failure, and dilated cardiomyopathy) as well as obesity, hyperlipidemia, diabetes and hyperhomocysteinemia. The aim of this work was to study the influence of potential metabolitotropic cardioprotector âAngiolinâ on the parameters of conjugate systems nitric oxide (NO)/restored thiols in heart under isadrine-pituitrin MI.Methods: This study was performed on Wistar white rats weighing 190-210 g. Biochemical, immune-enzyme analysis and histoimmunechemical study were performed.Results: In histological sections of hearts of the rats receiving Angiolin in parenteral dosing 50 mg/kg 30 mins before each pituitrin injection the density of endothelial NO-synthase (NOS)-positive cells increased by 29% and the density of inducible NOS-positive cells decreased by 23.3%. In cytosolic fraction of myocardium homogenate NOS activity increased by 27%, the concentration of NO stable metabolites increased by 70% and the content of nitrosative stress marker nitrotyrosine decreased by 42% when compared with control group. At the same time in similar samples of heart homogenate the increase of restored thiol groupsâ level by 53.3%, methionine - by 35.1%, cysteine - by 170% and activity of glutathione reductase - by 186% was noted. The administration of reference drug mildronate to the animals with MI in dose 100 mg/kg did not result in significant changes of the studied parameters of thiol-disulfide system and NO system of the heart when compared with control group.Conclusions: Angiolin does not influence directly on NOS in MI, but at the same time protects NO from nitrosative stress increasing restored equivalents of thiol-disulfide system
Development of biosensors for the determination of biologically active substances
Les biocapteurs sont des moyens dâanalyse en plein essor Ă la fois rapides, sĂ©lectifs et peu coĂ»teux applicables Ă des domaines extrĂȘmement variĂ©s (environnement, santĂ©, agroalimentaire,âŠ). Dans ce type dâoutil, un Ă©lĂ©ment sensible de nature biologique (anticorps, enzyme, microorganisme, ADNâŠ) dotĂ© dâun pouvoir de reconnaissance pour un analyte ou un groupe dâanalytes est associĂ© Ă un transducteur pouvant ĂȘtre de type Ă©lectrochimique, optique ou thermique.Dans ce travail, nous nous sommes intĂ©ressĂ©s au dĂ©veloppement de trois biocapteurs pour la dĂ©tection de substances biologiquement actives. Le premier permet la dĂ©termination simultanĂ©e de lâadĂ©nosine triphosphate (ATP) et du glucose par ampĂ©romĂ©trie, le deuxiĂšme celle de la crĂ©atine kinase, et le troisiĂšme est un biocapteur conductimĂ©tique pour la quantification de lâATP. Dans les deux premiers biocapteurs, deux enzymes (lâhexokinase et la glucose oxydase) sont immobilisĂ©es Ă la surface de microĂ©lectrodes constituĂ©es dâun disque de platine. Le troisiĂšme biocapteur est basĂ© sur lâimmobilisation de lâhexokinase sur des microĂ©lectrodes interdigitĂ©es en or. Lâimmobilisation est rĂ©alisĂ©e dans tous les cas par co-rĂ©ticulation des enzymes en prĂ©sence dâalbumine de sĂ©rum bovin Ă lâaide de glutaraldehyde. Les caractĂ©ristiques analytiques des biocapteurs ont Ă©tĂ© dĂ©terminĂ©es et diffĂ©rentes procĂ©dures ont Ă©tĂ© dĂ©veloppĂ©es pour lâanalyse dâĂ©chantillons rĂ©els. Les biocapteurs ont pu ĂȘtre appliquĂ©s avec succĂšs Ă la quantification de lâATP, du glucose et de la crĂ©atine kinase dans des prĂ©parations pharmaceutiques et du sĂ©rum sanguinBiosensors are rapid, selective and inexpensive devices that combine a biological recognition element, the so-called bioreceptor (e.g. enzymes, antibodies, DNA or microorganisms) to a physical transducer (e.g. electrochemical, optical, thermal or piezoelectrical). They can be used to detect one specific analyte or one family of analytes for a wide range of applications (e.g. environment, food, health). In this work, the detection of biologically active substances was targeted. A biosensor system for simultaneous determination of adenosine triphosphate (ATP) and glucose, a biosensor for creatine kinase analysis, and a novel conductometric biosensor for ATP determination were developed. In the first two biosensors, two enzymes (hexokinase and glucose oxidase) were immobilized at the surface of platinum disc microelectrodes for amperometric detection. The third biosensor was based on hexokinase immobilized onto gold interdigitated microelectrodes for conductometric detection. In all cases, the enzymes were co-immobilized with bovine serum albumin by cross-linking using glutaraldehyde. Analytical characteristics of the biosensors were determined and different procedures were developed for real samples analysis. The biosensors could be successfully applied to the determination of ATP, glucose, and creatine kinase in pharmaceutical samples and blood seru
Développement de biocapteurs pour la détermination de substances biologiquement actives
Biosensors are rapid, selective and inexpensive devices that combine a biological recognition element, the so-called bioreceptor (e.g. enzymes, antibodies, DNA or microorganisms) to a physical transducer (e.g. electrochemical, optical, thermal or piezoelectrical). They can be used to detect one specific analyte or one family of analytes for a wide range of applications (e.g. environment, food, health). In this work, the detection of biologically active substances was targeted. A biosensor system for simultaneous determination of adenosine triphosphate (ATP) and glucose, a biosensor for creatine kinase analysis, and a novel conductometric biosensor for ATP determination were developed. In the first two biosensors, two enzymes (hexokinase and glucose oxidase) were immobilized at the surface of platinum disc microelectrodes for amperometric detection. The third biosensor was based on hexokinase immobilized onto gold interdigitated microelectrodes for conductometric detection. In all cases, the enzymes were co-immobilized with bovine serum albumin by cross-linking using glutaraldehyde. Analytical characteristics of the biosensors were determined and different procedures were developed for real samples analysis. The biosensors could be successfully applied to the determination of ATP, glucose, and creatine kinase in pharmaceutical samples and blood serumLes biocapteurs sont des moyens dâanalyse en plein essor Ă la fois rapides, sĂ©lectifs et peu coĂ»teux applicables Ă des domaines extrĂȘmement variĂ©s (environnement, santĂ©, agroalimentaire,âŠ). Dans ce type dâoutil, un Ă©lĂ©ment sensible de nature biologique (anticorps, enzyme, microorganisme, ADNâŠ) dotĂ© dâun pouvoir de reconnaissance pour un analyte ou un groupe dâanalytes est associĂ© Ă un transducteur pouvant ĂȘtre de type Ă©lectrochimique, optique ou thermique.Dans ce travail, nous nous sommes intĂ©ressĂ©s au dĂ©veloppement de trois biocapteurs pour la dĂ©tection de substances biologiquement actives. Le premier permet la dĂ©termination simultanĂ©e de lâadĂ©nosine triphosphate (ATP) et du glucose par ampĂ©romĂ©trie, le deuxiĂšme celle de la crĂ©atine kinase, et le troisiĂšme est un biocapteur conductimĂ©tique pour la quantification de lâATP. Dans les deux premiers biocapteurs, deux enzymes (lâhexokinase et la glucose oxydase) sont immobilisĂ©es Ă la surface de microĂ©lectrodes constituĂ©es dâun disque de platine. Le troisiĂšme biocapteur est basĂ© sur lâimmobilisation de lâhexokinase sur des microĂ©lectrodes interdigitĂ©es en or. Lâimmobilisation est rĂ©alisĂ©e dans tous les cas par co-rĂ©ticulation des enzymes en prĂ©sence dâalbumine de sĂ©rum bovin Ă lâaide de glutaraldehyde. Les caractĂ©ristiques analytiques des biocapteurs ont Ă©tĂ© dĂ©terminĂ©es et diffĂ©rentes procĂ©dures ont Ă©tĂ© dĂ©veloppĂ©es pour lâanalyse dâĂ©chantillons rĂ©els. Les biocapteurs ont pu ĂȘtre appliquĂ©s avec succĂšs Ă la quantification de lâATP, du glucose et de la crĂ©atine kinase dans des prĂ©parations pharmaceutiques et du sĂ©rum sangui
Développement de biocapteurs pour la détermination de substances biologiquement actives
Biosensors are rapid, selective and inexpensive devices that combine a biological recognition element, the so-called bioreceptor (e.g. enzymes, antibodies, DNA or microorganisms) to a physical transducer (e.g. electrochemical, optical, thermal or piezoelectrical). They can be used to detect one specific analyte or one family of analytes for a wide range of applications (e.g. environment, food, health). In this work, the detection of biologically active substances was targeted. A biosensor system for simultaneous determination of adenosine triphosphate (ATP) and glucose, a biosensor for creatine kinase analysis, and a novel conductometric biosensor for ATP determination were developed. In the first two biosensors, two enzymes (hexokinase and glucose oxidase) were immobilized at the surface of platinum disc microelectrodes for amperometric detection. The third biosensor was based on hexokinase immobilized onto gold interdigitated microelectrodes for conductometric detection. In all cases, the enzymes were co-immobilized with bovine serum albumin by cross-linking using glutaraldehyde. Analytical characteristics of the biosensors were determined and different procedures were developed for real samples analysis. The biosensors could be successfully applied to the determination of ATP, glucose, and creatine kinase in pharmaceutical samples and blood serumLes biocapteurs sont des moyens dâanalyse en plein essor Ă la fois rapides, sĂ©lectifs et peu coĂ»teux applicables Ă des domaines extrĂȘmement variĂ©s (environnement, santĂ©, agroalimentaire,âŠ). Dans ce type dâoutil, un Ă©lĂ©ment sensible de nature biologique (anticorps, enzyme, microorganisme, ADNâŠ) dotĂ© dâun pouvoir de reconnaissance pour un analyte ou un groupe dâanalytes est associĂ© Ă un transducteur pouvant ĂȘtre de type Ă©lectrochimique, optique ou thermique.Dans ce travail, nous nous sommes intĂ©ressĂ©s au dĂ©veloppement de trois biocapteurs pour la dĂ©tection de substances biologiquement actives. Le premier permet la dĂ©termination simultanĂ©e de lâadĂ©nosine triphosphate (ATP) et du glucose par ampĂ©romĂ©trie, le deuxiĂšme celle de la crĂ©atine kinase, et le troisiĂšme est un biocapteur conductimĂ©tique pour la quantification de lâATP. Dans les deux premiers biocapteurs, deux enzymes (lâhexokinase et la glucose oxydase) sont immobilisĂ©es Ă la surface de microĂ©lectrodes constituĂ©es dâun disque de platine. Le troisiĂšme biocapteur est basĂ© sur lâimmobilisation de lâhexokinase sur des microĂ©lectrodes interdigitĂ©es en or. Lâimmobilisation est rĂ©alisĂ©e dans tous les cas par co-rĂ©ticulation des enzymes en prĂ©sence dâalbumine de sĂ©rum bovin Ă lâaide de glutaraldehyde. Les caractĂ©ristiques analytiques des biocapteurs ont Ă©tĂ© dĂ©terminĂ©es et diffĂ©rentes procĂ©dures ont Ă©tĂ© dĂ©veloppĂ©es pour lâanalyse dâĂ©chantillons rĂ©els. Les biocapteurs ont pu ĂȘtre appliquĂ©s avec succĂšs Ă la quantification de lâATP, du glucose et de la crĂ©atine kinase dans des prĂ©parations pharmaceutiques et du sĂ©rum sangui
ï»żInfluence of experimental heart failure therapy with different generations of ÎČ-adrenergic blockers on Cardiac Electrical Activity (ECG) and Autonomic Regulation of Heart Rhythm (ARHR)
Abstract: In the complex treatment of chronic heart failure (CHF) ÎČ-adrenoblockers (carvedilol, nebivolol, bisoprolol, metoprolol) are used, which due to their pharmacological properties increase the survival rate of patients, improve cardio- and haemodynamic parameters, metabolism. However, modern realities in medicine require creation of new more effective and safe ÎČ-adrenoblockers. In this regard, the potential drug Hypertirl is of interest. The aim was to evaluate the cardioprotective effect of 1-(b-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril) on cardiac electrical activity and autonomic regulation of heart rhythm in a model of CHF in comparison with ÎČ-adrenoblockers of different generations (Nebivolol, Carvedilol, Bisoprolol, Metoprolol). Materials and methods: Chronic heart failure was induced by 14-day administration of doxorubicin in a cumulative dose of 15 mg/kg to white mongrel rats weighing 190â220g (total 85). The investigated drugs were administered after doxorubicin course for 30 days: Hypertril at an experimentally substantiated dose of 3.5 mg/kg, Metoprolol succinate 15 mg/kg, Nebivolol 10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol 10 mg/kg. At the end of drug administration under thiopental anaesthesia (40 mg/kg), electrocardiogram (ECG) and autonomic regulation of heart rhythm (ARHR) were analysed using a computer analyser CardioCom-2000plus (KAI-Medica, Ukraine). The results of the study were calculated using a standard statistical package âSTATISTICA for Windows 6.0â (StatSoftInc., âAXXR712D833214FAN5), âSPSS 16.0â and âMicrosoft Office Excell 2003â. Results and discussion: Hypertril administration resulted in a negative chronotropic effect, normalisation of atrial (P) and ventricular (R) spike amplitude, ST segment inversion below isoline, increased amplitude of ventricular myocardial repolarisation T. Myocardial repolarisation spike were observed, as well as normalised the duration of atrial (P) and ventricular depolarisation phase (QRS complex) to the intact value and restored the duration of electrical diastole (TR interval). Hypertril reduced systolic and diastolic myocardial dysfunction in animals with CHF. Hypertril restored autonomic mechanisms of heart rhythm regulation and balanced activity of sympathetic and parasympathetic parts of autonomic nervous system in the control of cardiac function. Conclusion: The obtained results demonstrated the undoubted advantage of the new original molecule (Hypertril) over basic ÎČ-adrenoblockers (Metoprolol, Nebivolol, Carvedilol and Bisoprolol) and experimentally justify further in-depth study to create on its basis a drug for the treatment of CHF
A novel urea conductometric biosensor based on zeolite immobilized urease
A new approach was developed for urea determination where a thin film of silicalite and zeolite Beta deposited onto gold electrodes of a conductometric biosensor was used to immobilize the enzyme. Biosensor responses, operational and storage stabilities were compared with results obtained from the standard membrane methods for the same measurements. For this purpose, different surface modification techniques, which are simply named as Zeolite Membrane Transducers (ZMTs) and Zeolite Coated Transducers (ZCTs) were compared with Standard Membrane Transducers (SMTs). Silicalite and zeolite Beta with Si/Al ratios 40, 50 and 60 were used to modify the conductometric electrodes and to study the biosensor responses as a function of changing zeolitic parameters. During the measurements using ZCT electrodes, there was no need for any cross-linker to immobilize urease, which allowed the direct evaluation of the effect of changing Si/Al ratio for the same type of zeolite on the biosensor responses for the first time. It was seen that silicalite and zeolite Beta added electrodes in all cases lead to increased responses with respect to SMTs. The responses obtained from ZCTs were always higher than ZMTs as well. The responses obtained from zeolite Beta modified ZMTs and ZCTs increased as a function of increasing Si/Al ratio, which might be due to the increased hydrophobicity and/or the acid strength of the medium
Determination of total creatine kinase activity in blood serum using an amperometric biosensor based on glucose oxidase and hexokinase
International audienceCreatine kinase (CK: adenosine-5-triphosphate-creatine phosphotransferase) is an important enzyme of muscle cells; the presence of a large amount of the enzyme in blood serum is a biomarker of muscular injuries, such as acute myocardial infarction. This work describes a bi-enzyme (glucose oxidase and hexokinase based) biosensor for rapid and convenient determination of CK activity by measuring the rate of ATP production by this enzyme. Simultaneously the biosensor determines glucose concentration in the sample. Platinum disk electrodes were used as amperometric transducers. Glucose oxidase and hexokinase were co-immobilized via cross-linking with BSA by glutaraldehyde and served as a biorecognition element of the biosensor. The biosensor work at different concentrations of CK substrates (ADP and creatine phosphate) was investigated; optimal concentration of ADP was 1 mM, and creatine phosphate - 10 mM. The reproducibility of the biosensor responses to glucose, ATP and CK during a day was tested (relative standard deviation of 15 responses to glucose was 2%, to ATP - 6%, to CM - 7-18% depending on concentration of the CK). Total time of CM analysis was 10 min. The measurements of creatine kinase in blood serum samples were carried out (at 20-fold sample dilution). Twentyfold dilution of serum samples was chosen as optimal for CM determination. The biosensor could distinguish healthy and ill people and evaluate the level of CM increase. Thus, the biosensor can be used as a test-system for CM analysis in blood serum or serve as a component of multibiosensors for determination of important blood substances. Determination of activity of other kinases by the developed biosensor is also possible for research purpose
IonâSelective Sensors Based on LaserâInduced Graphene for Evaluating Human Hydration Levels Using Urine Samples
Complex graphene electrode fabrication protocols including conventional chemical vapor deposition and graphene transfer techniques as well as more recent solutionâphase printing and postprint annealing methods have hindered the wideâscale implementation of electrochemical devices including solidâstate ionâselective electrodes (ISEs). Herein, a facile graphene ISE fabrication technique that utilizes laser induced graphene (LIG), formed by converting polyimide into graphene by a CO2 laser and functionalization with ammonium ion (NH4+) and potassium ion (K+) ionâselective membranes, is demonstrated. The electrochemical LIG ISEs exhibit a wide sensing range (0.1 Ă 10â3â150 Ă 10â3 m for NH4+ and 0.3 Ă 10â3â150 Ă 10â3 m for K+) with high stability (minimal drop in signal after 3 months of storage) across a wide pH range (3.5â9.0). The LIG ISEs are also able to monitor the concentrations of NH4+ and K+ in urine samples (29â51% and 17â61% increase for the younger and older patient; respectively, after dehydration induction), which correlate well with conventional hydration status measurements. Hence, these results demonstrate a facile method to perform inâfield ion sensing and are the first steps in creating a protocol for quantifying hydration levels through urine testing in human subjects.This is the peer-reviewed version of the following article: Kucherenko, Ivan S., Delaney Sanborn, Bolin Chen, Nate Garland, Michael Serhan, Erica Forzani, Carmen Gomes, and Jonathan C. Claussen. "IonâSelective Sensors Based on LaserâInduced Graphene for Evaluating Human Hydration Levels Using Urine Samples." Advanced Materials Technologies 5, no. 6 (2020): 1901037, which has been published in final form at DOI: 10.1002/admt.201901037. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Posted with permission.</p