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Volume 69 (2022): Edizione 2 (August 2022)

Volume 69 (2022): Edizione s1 (July 2022)

Volume 69 (2022): Edizione 1 (January 2022)

Volume 68 (2021): Edizione 2 (December 2021)

Volume 68 (2021): Edizione 1 (January 2021)

Volume 67 (2020): Edizione 2 (May 2020)

Volume 67 (2020): Edizione 1 (January 2020)

Volume 66 (2019): Edizione 2 (November 2019)

Volume 66 (2019): Edizione 1 (June 2019)

Volume 65 (2018): Edizione 2 (November 2018)

Volume 65 (2018): Edizione 1 (June 2018)

Volume 64 (2017): Edizione 2 (November 2017)

Volume 64 (2017): Edizione 1 (September 2017)

Volume 63 (2016): Edizione s12 (December 2016)

Volume 63 (2016): Edizione 2 (December 2016)

Volume 63 (2016): Edizione 1 (September 2016)

Volume 62 (2015): Edizione s10 (September 2015)

Volume 62 (2015): Edizione s9 (June 2015)

Volume 62 (2015): Edizione 2 (December 2015)

Volume 62 (2015): Edizione 1 (June 2015)

Volume 61 (2014): Edizione 2 (December 2014)

Volume 61 (2014): Edizione 1 (August 2014)

Volume 60 (2013): Edizione Supplementum-VIII (March 2013)
Rare disease day in Slovakia, Europlan national conference

Volume 60 (2013): Edizione 2 (December 2013)

Volume 60 (2013): Edizione 1 (June 2013)

Volume 59 (2012): Edizione Supplement-VII (February 2012)
Conference abstracts, Rare disease day, conference 29.2.2012, First Slovak conference about rare diseases

Volume 59 (2012): Edizione Supplement-VI (January 2012)
Clinical Pharmacy in the Slovak Republic, dedicated to the associated professor Lívia Magulová, PhD.

Volume 59 (2012): Edizione 2 (November 2012)

Volume 59 (2012): Edizione 1 (June 2012)

Volume 58 (2011): Edizione 1 (January 2011)

Dettagli della rivista
Formato
Rivista
eISSN
2453-6725
ISSN
0301-2298
Pubblicato per la prima volta
25 Nov 2011
Periodo di pubblicazione
2 volte all'anno
Lingue
Inglese

Cerca

Volume 60 (2013): Edizione 2 (December 2013)

Dettagli della rivista
Formato
Rivista
eISSN
2453-6725
ISSN
0301-2298
Pubblicato per la prima volta
25 Nov 2011
Periodo di pubblicazione
2 volte all'anno
Lingue
Inglese

Cerca

8 Articoli
access type Accesso libero

Antimicrobial susceptibility and immunomodulatory properties of lamb isolate of lactobacillus mucosae, new probiotic candidate

Pubblicato online: 31 Dec 2013
Pagine: 1 - 6

Astratto

Abstract

In the process of selecting a new probiotic candidate, several bacteria were isolated from the stomach mucosa of a lamb. Among them, three lactobacilli strains were identified and partially characterised. The strain, Lactobacillus mucosae D, showed several characteristics appropriate to the probiotics. In this study, we have focused on the further characterisation of L. mucosae D and testing of its ability to modulate metabolic and immunomodulatory activities of human mononuclear cells in vitro. L. mucosae D is resistant to antibiotics, like penicillin G, oxacillin, vancomycin and chemotherapeutics ofloxacin and ciprofloxacin. In in vitro conditions, L. mucosae D caused a significant increase in phagocytic activity and index (relative activities 1.05 and 1.44, respectively) of human monocytes. It decreased bactericidal activities of monocytes against Escherichia coli (relative activity 0.73) and Staphylococcus aureus (relative activity 0.36), whereas, candidacidal activity was enhanced (relative activity 1.15). Metabolic activities, lysozyme and peroxidase activity, of mononuclear cells were not changed or increased, respectively. L. mucosae D displayed the ability to enhance production of pro-inflammatory cytokine, IL-1β, in monocytes in vitro (relative activity 2.60). Therefore, we state that lamb isolate, L. mucosae D, has the required attributes for being a potential probiotic candidate.

Parole chiave

  • Lactobacillus mucosae
  • probiotics
  • immunomodulation

Klúcové slová

  • Lactobacillus mucosae
  • probiotiká
  • imunomodulácia
access type Accesso libero

Effect of N-dodecyl-N,N-dimethylamine N-oxide on unilamellar liposomes

Pubblicato online: 31 Dec 2013
Pagine: 7 - 13

Astratto

Abstract

The effect of N-dodecyl-N,N-dimethylamine N-oxide (C12NO) on the unilamellar liposomes prepared from egg yolk phosphatidylcholine (EYPC) was studied using turbidimetric and fluorescence spectroscopic methods. The concentrations of C12NO causing saturation and total solubilization of membrane were evaluated turbidimetrically. Liposomes filled with hydrophilic fluorescent probe calcein were used for the fluorescence leakage measurements. Dependence of fluorescence intensity on C12NO concentration can be divided into three linear sections. The turning points between individual sections represent two concentrations of C12NO which induce formation of small defects, specifically large pores in liposomal membrane. These pores are wide enough to enable calcein to be washed out from liposomes completely. We compared results obtained by the two methods used. Measurements of fluorescent probe leakage showed that free diffusion of calcein through pores in EYPC bilayer was observed at such C12NO concentrations when the form of liposome is still preserved and the saturation of bilayer is not yet finished. Higher C12NO concentrations are needed for solubilization, a phase transition from bilayers to micelles.

Parole chiave

  • unilamellar liposomes - solubilization - calcein - N-dodecyl-N,N-dimethylamine N-oxide

Klúcové slová

  • unilamelárne lipozómy - solubilizácia - kalceín - N-dodecyl-N,N-dimetylamín N-oxid
access type Accesso libero

Carvedilol and Pycnogenol® improve the function of diabetic hearts in rats

Pubblicato online: 31 Dec 2013
Pagine: 15 - 21

Astratto

Abstract

We observed the changes in electrical activity, biometric and haemodynamic parameters of hearts in animals with experimental diabetes mellitus (DM). As well the effect of carvedilol, PycnogenolR and its combination with carvedilol on DM heart function was tested. DM was induced by streptozotocin over three sequential days at a dose of 25 mg/kg body weight i.p. We started therapy by suspension of carvedilol, PycnogenolR and their combination for six weeks. Blood pressure was measured using tail cuff plethysmography. ECG, haemodynamic and biometric parameters were measured in isolated hearts perfused according to the Langendorff. DM rats had increased systolic arterial blood pressure, thicker free wall of left ventricle but weakened myocardial contractility compared with controls. In contrast to controls, electrophysiological parameters showed prolonged QT interval and increased incidence of dysrhythmias in DM rats. The PycnogenolR administration induced regression of left ventricular hypertrophy, improved left ventriculi contraction and increased coronary flow; however, it did not improve the electrical activity of the myocardium compared with DM ones. Carvedilol also reversed the myocardial remodelling, shortened the duration of QT interval and suppressed the incidence of dysrhythmias. The common combination of drugs improved biometric and haemodynamic parameters compared with DM animals, however, not so significantly as monotherapy. On the other hand, the combination of carvedilol and PycnogenolR significantly reduced the duration of the QT interval and shortened the incidence of dysrhythmias. We can conclude that the administration of PycnogenolR effectively improved haemodynamic parameters, and carvedilol affected biometric parameters and also electrical parameters in DM animals. We observed the marked synergic effect of the combination of both drugs on the electrical activity of myocardium. This combination shortened the most pathologically prolonged QT interval and reduced the number of dysrhythmias.

Keywords

  • diabetes mellitus - ECG - carvedilol - Pycnogenol® - rat

Klúcové slová

  • diabetes mellitus - EKG - karvedilol - Pycnogenol® - potkan
access type Accesso libero

Analysis of individually prepared medicines prescription in community pharmacy

Pubblicato online: 31 Dec 2013
Pagine: 23 - 27

Astratto

Abstract

Our study deals with the analysis of prescription of individually prepared medicines (IPMs) in selected community pharmacies in Slovakia and Greece during the year 2011. Throughout the given period, the total sum of processed medical prescriptions in selected Slovak pharmacies was 50,992, while in Greece it was 45,862 prescriptions. Out of the total sum of prescriptions, we selected those with prescribed IPMs. In our study, we further analysed the representation of individual age groups and both genders in prescriptions of the IPMs. Next, we examined the frequency of IPM prescriptions based on specialisation of the prescribing physicians and the most frequent diagnoses for which the IPMs were prescribed. Further, we classified the prescribed IPMs into specific groups according to their drug forms. In our study, we also described the representation of individual drug forms (oral, cutaneous and for specific use) and representation of prepared or adjusted IPMs. The relevance of this topic is supported by marked decrease of rate of preparing of IPMs in the last decades as well as by necessity to preserve it for reasons such as certain diagnoses, technological and economic aspects and differences among age groups require distinctive specification of the prepared medicines.

Keywords

  • individually prepared medicines - medical prescription - prescription of IPM - community pharmacy - Slovakia - Greece

Klúcové slová

  • individuálne pripravované lieky - lekársky predpis - preskripcia IPL - verejná lekáreň - Slovensko - Grécko
access type Accesso libero

Radionuclide x-ray fluorescence analysis of selected elements in agrimony tea samples with preconcentration

Pubblicato online: 31 Dec 2013
Pagine: 29 - 36

Astratto

Abstract

The contents of selected elements (Mn, Fe, Co, Ni, Cu, Zn, Hg and Pb) in samples of loose tea of agrimony “Repikovy čaj” (Agrimonia eupatoria L.) were studied in this work. Identification and determination of the selected elements content were performed using X-ray fluorescence spectrometry - the nuclear analytical method based on the interaction between low-energy gamma and X radiation and analysed substance. Solid form samples were pressed in tablets and directly analysed. Prepared infusions were analysed after the preconcentration of the elements using precipitation with thioacetamide and ammonium diethyldithiocarbamate with subsequent filtration of created precipitates through a nitrocellulose filter. Detection limits obtained from both methods were compared and their suitability for elemental analysis of plant preparations was discussed.

Parole chiave

  • heavy metals - preconcentration - Agrimonia eupatoria L. - XRFS - medicinal plants

Klúcové slová

  • ťažké kovy - zakoncentrovanie - Agrimonia eupatoria L. - RRFS - liečivé rastliny
access type Accesso libero

Synthesis of new compounds of the aryloxyaminopropanol type and their HPLC enantioseparation

Pubblicato online: 31 Dec 2013
Pagine: 37 - 42

Astratto

Abstract

This article describes a preparation of some new compounds of the aryloxyaminopropanol type derived from 4-hydroxyphenylpropan- 1-one with phenylamino, cyclohexylamino and isobutylamino group in the hydrophilic part and methoxymethyl or ethoxymethyl substituent in the lipophilic part of the molecule. The purity of the prepared compounds was checked by thinlayer chromatography and the structure was confirmed on the basis of interpretation of the IR, UV, 1H NMR and 13C NMR spectra. An enantioseparation of the prepared compounds was performed by using high-performance liquid chromatography on an amylase tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) and native teicoplanin (Chirobiotic T). The chromatographic results such as retention, separation and resolution factors have shown that Chiralpak AD is more suitable for enantioseparation of some of the prepared compounds.

Parole chiave

  • aryloxyaminopropanol - enantioseparation - HPLC - Chirobiotic T - Chiralpak AD

Klúcové slová

  • aryloxyaminopropanoly - enantioseparácia - HPLC - Chirobiotic T - Chiralpak AD
access type Accesso libero

Isothermal and non-isothermal kinetics of hydrolysis of 1-[2-(2- pentyloxyphenylcarbamoyloxy)-(2-methoxymethyl)-ethyl]- perhydroazepinium chloride (BK 129)

Pubblicato online: 31 Dec 2013
Pagine: 43 - 48

Astratto

Abstract

The substance BK 129 - 1-[2-(2-pentyloxyphenylcarbamoyloxy)-(2-methoxymethyl)-ethyl]-perhydroazepinium chloride was prepared in terms of influence of the connecting chain between the carbamate functional group and the basic part of molecule on biological activity. Such a structural feature is important with regard to its stability. In this work we determined the rate constants of alkaline hydrolysis of this compound at increased temperature under isothermal and non-isothermal conditions. The hydrolysis was also performed in buffer solutions with the purpose of evaluating its stability. Non-isothermal tests of stability enable to reduce the number of analyses. The necessary data for stability of compound are in this way achieved in a short time.

Parole chiave

  • antiarrhythmics - stability study - kinetics of hydrolysis - non-isothermal kinetics

Klúcové slová

  • antiarytmika - študia stability - kinetika hydrolyzy - neizotermicka kinetika
access type Accesso libero

Involvement of the vanilloid receptor 1 in the mechanism of analgetic effect of ketorolac

Pubblicato online: 31 Dec 2013
Pagine: 49 - 55

Astratto

Abstract

The existing ideas about the ketorolac mechanism of analgetic potency are associated with its effect on COX isoenzymes and its significant potency needs to be explained more completely. Its impact on vanilloid receptors 1 (TRPV1) can also be an effective mechanism of analgetic action. We have evaluated the analgetic potential of ketorolac on the basis of its influence on TRPV1. It is known that Tyr511 and Ser512 amino acids are active central components of TRPV1. Thereby the synthesis of the dipeptide Tyr-Ser has been conducted as a model of the TRPV1 active centre. In our model test, using spectrofluorometry, the formation of intermolecular complexes was shown: “ketorolac - Tyr-Ser” and “capsaicin - Tyr-Ser” at stability constants Kr=0.53 • 10-4 L/mol; Kkor= 0.998 and Kr =0.3 • 10-4 L/mol; Kkor=0.998, respectively. Verification of the data was proved in experiments in vitro (the preparation of portal vein) and in vivo (Tail-flick model), with the TRPV1 agonist and antagonist. On portal vein, it was established (from initial level) by Krebs solution that the range of relaxation of smooth muscles of the portal vein (SM) was as follows at the concentration of capsaicin 0.1 μmol/L +30.3%±5.3%, capsazepine 0.5 μmol/L -3.2±2.7% and ketorolac 1.0 μmol/L -60.0±7.0%. In the experiment, at the above mentioned doses of ketorolac on the background of the action of the capsaicin (capsazepine), the range of relaxation of smooth muscles (SM) of the portal vein was -59.3±5.0% and -63.0±6.0% respectively testifying to the fact that the effect of capsaicinoids was neutralised by ketorolac. On the Tail-flick model, an atypical potentiation of the ketorolac antinociception at simultaneous use with the capsaicin was shown. The obtained data allow suggesting that TRPV1 can activate the ketorolac antinociceptive effects.

Keywords

  • ketorolac
  • capsaicin
  • capsazepine
  • dipeptide Tyr-Ser (Tyr-Ser)
  • TRPV1
8 Articoli
access type Accesso libero

Antimicrobial susceptibility and immunomodulatory properties of lamb isolate of lactobacillus mucosae, new probiotic candidate

Pubblicato online: 31 Dec 2013
Pagine: 1 - 6

Astratto

Abstract

In the process of selecting a new probiotic candidate, several bacteria were isolated from the stomach mucosa of a lamb. Among them, three lactobacilli strains were identified and partially characterised. The strain, Lactobacillus mucosae D, showed several characteristics appropriate to the probiotics. In this study, we have focused on the further characterisation of L. mucosae D and testing of its ability to modulate metabolic and immunomodulatory activities of human mononuclear cells in vitro. L. mucosae D is resistant to antibiotics, like penicillin G, oxacillin, vancomycin and chemotherapeutics ofloxacin and ciprofloxacin. In in vitro conditions, L. mucosae D caused a significant increase in phagocytic activity and index (relative activities 1.05 and 1.44, respectively) of human monocytes. It decreased bactericidal activities of monocytes against Escherichia coli (relative activity 0.73) and Staphylococcus aureus (relative activity 0.36), whereas, candidacidal activity was enhanced (relative activity 1.15). Metabolic activities, lysozyme and peroxidase activity, of mononuclear cells were not changed or increased, respectively. L. mucosae D displayed the ability to enhance production of pro-inflammatory cytokine, IL-1β, in monocytes in vitro (relative activity 2.60). Therefore, we state that lamb isolate, L. mucosae D, has the required attributes for being a potential probiotic candidate.

Parole chiave

  • Lactobacillus mucosae
  • probiotics
  • immunomodulation

Klúcové slová

  • Lactobacillus mucosae
  • probiotiká
  • imunomodulácia
access type Accesso libero

Effect of N-dodecyl-N,N-dimethylamine N-oxide on unilamellar liposomes

Pubblicato online: 31 Dec 2013
Pagine: 7 - 13

Astratto

Abstract

The effect of N-dodecyl-N,N-dimethylamine N-oxide (C12NO) on the unilamellar liposomes prepared from egg yolk phosphatidylcholine (EYPC) was studied using turbidimetric and fluorescence spectroscopic methods. The concentrations of C12NO causing saturation and total solubilization of membrane were evaluated turbidimetrically. Liposomes filled with hydrophilic fluorescent probe calcein were used for the fluorescence leakage measurements. Dependence of fluorescence intensity on C12NO concentration can be divided into three linear sections. The turning points between individual sections represent two concentrations of C12NO which induce formation of small defects, specifically large pores in liposomal membrane. These pores are wide enough to enable calcein to be washed out from liposomes completely. We compared results obtained by the two methods used. Measurements of fluorescent probe leakage showed that free diffusion of calcein through pores in EYPC bilayer was observed at such C12NO concentrations when the form of liposome is still preserved and the saturation of bilayer is not yet finished. Higher C12NO concentrations are needed for solubilization, a phase transition from bilayers to micelles.

Parole chiave

  • unilamellar liposomes - solubilization - calcein - N-dodecyl-N,N-dimethylamine N-oxide

Klúcové slová

  • unilamelárne lipozómy - solubilizácia - kalceín - N-dodecyl-N,N-dimetylamín N-oxid
access type Accesso libero

Carvedilol and Pycnogenol® improve the function of diabetic hearts in rats

Pubblicato online: 31 Dec 2013
Pagine: 15 - 21

Astratto

Abstract

We observed the changes in electrical activity, biometric and haemodynamic parameters of hearts in animals with experimental diabetes mellitus (DM). As well the effect of carvedilol, PycnogenolR and its combination with carvedilol on DM heart function was tested. DM was induced by streptozotocin over three sequential days at a dose of 25 mg/kg body weight i.p. We started therapy by suspension of carvedilol, PycnogenolR and their combination for six weeks. Blood pressure was measured using tail cuff plethysmography. ECG, haemodynamic and biometric parameters were measured in isolated hearts perfused according to the Langendorff. DM rats had increased systolic arterial blood pressure, thicker free wall of left ventricle but weakened myocardial contractility compared with controls. In contrast to controls, electrophysiological parameters showed prolonged QT interval and increased incidence of dysrhythmias in DM rats. The PycnogenolR administration induced regression of left ventricular hypertrophy, improved left ventriculi contraction and increased coronary flow; however, it did not improve the electrical activity of the myocardium compared with DM ones. Carvedilol also reversed the myocardial remodelling, shortened the duration of QT interval and suppressed the incidence of dysrhythmias. The common combination of drugs improved biometric and haemodynamic parameters compared with DM animals, however, not so significantly as monotherapy. On the other hand, the combination of carvedilol and PycnogenolR significantly reduced the duration of the QT interval and shortened the incidence of dysrhythmias. We can conclude that the administration of PycnogenolR effectively improved haemodynamic parameters, and carvedilol affected biometric parameters and also electrical parameters in DM animals. We observed the marked synergic effect of the combination of both drugs on the electrical activity of myocardium. This combination shortened the most pathologically prolonged QT interval and reduced the number of dysrhythmias.

Keywords

  • diabetes mellitus - ECG - carvedilol - Pycnogenol® - rat

Klúcové slová

  • diabetes mellitus - EKG - karvedilol - Pycnogenol® - potkan
access type Accesso libero

Analysis of individually prepared medicines prescription in community pharmacy

Pubblicato online: 31 Dec 2013
Pagine: 23 - 27

Astratto

Abstract

Our study deals with the analysis of prescription of individually prepared medicines (IPMs) in selected community pharmacies in Slovakia and Greece during the year 2011. Throughout the given period, the total sum of processed medical prescriptions in selected Slovak pharmacies was 50,992, while in Greece it was 45,862 prescriptions. Out of the total sum of prescriptions, we selected those with prescribed IPMs. In our study, we further analysed the representation of individual age groups and both genders in prescriptions of the IPMs. Next, we examined the frequency of IPM prescriptions based on specialisation of the prescribing physicians and the most frequent diagnoses for which the IPMs were prescribed. Further, we classified the prescribed IPMs into specific groups according to their drug forms. In our study, we also described the representation of individual drug forms (oral, cutaneous and for specific use) and representation of prepared or adjusted IPMs. The relevance of this topic is supported by marked decrease of rate of preparing of IPMs in the last decades as well as by necessity to preserve it for reasons such as certain diagnoses, technological and economic aspects and differences among age groups require distinctive specification of the prepared medicines.

Keywords

  • individually prepared medicines - medical prescription - prescription of IPM - community pharmacy - Slovakia - Greece

Klúcové slová

  • individuálne pripravované lieky - lekársky predpis - preskripcia IPL - verejná lekáreň - Slovensko - Grécko
access type Accesso libero

Radionuclide x-ray fluorescence analysis of selected elements in agrimony tea samples with preconcentration

Pubblicato online: 31 Dec 2013
Pagine: 29 - 36

Astratto

Abstract

The contents of selected elements (Mn, Fe, Co, Ni, Cu, Zn, Hg and Pb) in samples of loose tea of agrimony “Repikovy čaj” (Agrimonia eupatoria L.) were studied in this work. Identification and determination of the selected elements content were performed using X-ray fluorescence spectrometry - the nuclear analytical method based on the interaction between low-energy gamma and X radiation and analysed substance. Solid form samples were pressed in tablets and directly analysed. Prepared infusions were analysed after the preconcentration of the elements using precipitation with thioacetamide and ammonium diethyldithiocarbamate with subsequent filtration of created precipitates through a nitrocellulose filter. Detection limits obtained from both methods were compared and their suitability for elemental analysis of plant preparations was discussed.

Parole chiave

  • heavy metals - preconcentration - Agrimonia eupatoria L. - XRFS - medicinal plants

Klúcové slová

  • ťažké kovy - zakoncentrovanie - Agrimonia eupatoria L. - RRFS - liečivé rastliny
access type Accesso libero

Synthesis of new compounds of the aryloxyaminopropanol type and their HPLC enantioseparation

Pubblicato online: 31 Dec 2013
Pagine: 37 - 42

Astratto

Abstract

This article describes a preparation of some new compounds of the aryloxyaminopropanol type derived from 4-hydroxyphenylpropan- 1-one with phenylamino, cyclohexylamino and isobutylamino group in the hydrophilic part and methoxymethyl or ethoxymethyl substituent in the lipophilic part of the molecule. The purity of the prepared compounds was checked by thinlayer chromatography and the structure was confirmed on the basis of interpretation of the IR, UV, 1H NMR and 13C NMR spectra. An enantioseparation of the prepared compounds was performed by using high-performance liquid chromatography on an amylase tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) and native teicoplanin (Chirobiotic T). The chromatographic results such as retention, separation and resolution factors have shown that Chiralpak AD is more suitable for enantioseparation of some of the prepared compounds.

Parole chiave

  • aryloxyaminopropanol - enantioseparation - HPLC - Chirobiotic T - Chiralpak AD

Klúcové slová

  • aryloxyaminopropanoly - enantioseparácia - HPLC - Chirobiotic T - Chiralpak AD
access type Accesso libero

Isothermal and non-isothermal kinetics of hydrolysis of 1-[2-(2- pentyloxyphenylcarbamoyloxy)-(2-methoxymethyl)-ethyl]- perhydroazepinium chloride (BK 129)

Pubblicato online: 31 Dec 2013
Pagine: 43 - 48

Astratto

Abstract

The substance BK 129 - 1-[2-(2-pentyloxyphenylcarbamoyloxy)-(2-methoxymethyl)-ethyl]-perhydroazepinium chloride was prepared in terms of influence of the connecting chain between the carbamate functional group and the basic part of molecule on biological activity. Such a structural feature is important with regard to its stability. In this work we determined the rate constants of alkaline hydrolysis of this compound at increased temperature under isothermal and non-isothermal conditions. The hydrolysis was also performed in buffer solutions with the purpose of evaluating its stability. Non-isothermal tests of stability enable to reduce the number of analyses. The necessary data for stability of compound are in this way achieved in a short time.

Parole chiave

  • antiarrhythmics - stability study - kinetics of hydrolysis - non-isothermal kinetics

Klúcové slová

  • antiarytmika - študia stability - kinetika hydrolyzy - neizotermicka kinetika
access type Accesso libero

Involvement of the vanilloid receptor 1 in the mechanism of analgetic effect of ketorolac

Pubblicato online: 31 Dec 2013
Pagine: 49 - 55

Astratto

Abstract

The existing ideas about the ketorolac mechanism of analgetic potency are associated with its effect on COX isoenzymes and its significant potency needs to be explained more completely. Its impact on vanilloid receptors 1 (TRPV1) can also be an effective mechanism of analgetic action. We have evaluated the analgetic potential of ketorolac on the basis of its influence on TRPV1. It is known that Tyr511 and Ser512 amino acids are active central components of TRPV1. Thereby the synthesis of the dipeptide Tyr-Ser has been conducted as a model of the TRPV1 active centre. In our model test, using spectrofluorometry, the formation of intermolecular complexes was shown: “ketorolac - Tyr-Ser” and “capsaicin - Tyr-Ser” at stability constants Kr=0.53 • 10-4 L/mol; Kkor= 0.998 and Kr =0.3 • 10-4 L/mol; Kkor=0.998, respectively. Verification of the data was proved in experiments in vitro (the preparation of portal vein) and in vivo (Tail-flick model), with the TRPV1 agonist and antagonist. On portal vein, it was established (from initial level) by Krebs solution that the range of relaxation of smooth muscles of the portal vein (SM) was as follows at the concentration of capsaicin 0.1 μmol/L +30.3%±5.3%, capsazepine 0.5 μmol/L -3.2±2.7% and ketorolac 1.0 μmol/L -60.0±7.0%. In the experiment, at the above mentioned doses of ketorolac on the background of the action of the capsaicin (capsazepine), the range of relaxation of smooth muscles (SM) of the portal vein was -59.3±5.0% and -63.0±6.0% respectively testifying to the fact that the effect of capsaicinoids was neutralised by ketorolac. On the Tail-flick model, an atypical potentiation of the ketorolac antinociception at simultaneous use with the capsaicin was shown. The obtained data allow suggesting that TRPV1 can activate the ketorolac antinociceptive effects.

Keywords

  • ketorolac
  • capsaicin
  • capsazepine
  • dipeptide Tyr-Ser (Tyr-Ser)
  • TRPV1

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