Stanislava Jankyova | Comenius University in Bratislava (original) (raw)
Papers by Stanislava Jankyova
In order to reduce problems associated with potentially inappropriate medication prescribing in g... more In order to reduce problems associated with potentially inappropriate medication prescribing in geriatric patients, it´s necessary to establish appropriate regulatory measures and to increase training of medical doctors and pharmacists in problems of PIMs. Regulatory measures regarding PIM use widely differ across Europe. The aim of this study was to investigate what prescription limits are established for EU-7 PIMs in Central and Eastern European countries. To avoid ageism and ageist practices in inappropriate medication use in older patients, prescription limits for PIMs should be harmonized across Europe.
Poskodenie ciev predstavuje najcastejsiu komplikaciu diabetes mellitus (DM). Terapia DM sa preto ... more Poskodenie ciev predstavuje najcastejsiu komplikaciu diabetes mellitus (DM). Terapia DM sa preto orientuje nielen na upravu hodnot glykemie, ale aj na prevenciu a liecbu cievneho poskodenia. Niektore skupiny v sucasnosti použivaných antidiabetik maju endotelovoprotektivne vlastnosti, ktore nie su iba dosledkom ich ucinku na hladinu glykemie. Su perspektivnymi nastrojmi pre znižovanie kardiovaskularnej morbidity a mortality u diabetikov. Predložena praca sa zaobera jednotlivými skupinami antidiabetik z hľadiska ich vplyvu na endotelovu dysfunkciu u pacientov s DM 2. typu.
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2013
We observed the changes in electrical activity, biometric and haemodynamic parameters of hearts i... more 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...
Bratislava Medical Journal, 2014
Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of... more Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of both drugs is associated with increased risk of gastrointestinal (GI) bleeding. The administration of drugs inhibiting gastric acid production represents an effective way to avoid GI disorders associated with antiplatelet therapy. Objectives: The aim of our study was to evaluate the use of gastroprotective medication in elderly antiplatelet users in relation to risk factors for GI bleeding. Methods: Patients (n = 428) aged ≥ 65 years who were prescribed low dose ASA or clopidogrel in monotherapy or combination at hospital discharge were enrolled in the study. Results: Only 39.7 % of patients with 2 or more risk factors for GI bleeding were prescribed gastroprotective medication at hospital discharge. The probability of elderly antiplatelet drug user for prescription of gastroprotective medication was improved with following risk factors: age ≥ 85 years (OR = 2.99); history of peptic ulcer disease/ GI bleeding (OR = 15.79); other GI disorders (OR = 15.48); concomitant therapy with drugs increasing the risk of GI bleeding-systemic corticosteroids (OR = 29.03) and NSAIDs (OR = 4.79). Conclusion: Results of our study indicate the necessity to increase the awareness of GI bleeding risk in longterm antiplatelet users among prescribing physicians (Tab.
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2013
The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its abilit... more The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its ability to improve endothelial dysfunction in diabetic animals. The aim of this study was to isolate from Pycnogenol® mixture its active compounds and compare their efficacy on observed parameters. Pycnogenol® mixture was fractioned by re-extracting with petroleum ether, chloroform, ethyl acetate and butanol, subsequently. Pycnogenol® mixture and fractions (butanolic, water, ethyl acetate) were administered during 6 weeks to diabetic rats. Blood glucose levels were assessed from the arterio-venous blood at the beginning of experiment and at the end of experiment. Endothelial dysfunction was evaluated as the contractile responses to phenylephrine and acetylcholine. The amount of collagen I and III was assessed from thoracic aorta after picrosirius red staining. For the confirmation of the changes on molecular level, we determinated endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90...
Phytotherapy Research, 2009
We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin... more We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin‐induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)‐producing molecules (gp91phox‐containing NADPH oxidase and NO‐signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha‐tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect ...
Pathology - Research and Practice, 2012
Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by... more Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark - Pycnogenol(®) (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and significantly increased mean arterial blood pressure (by 19%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.
Bratislavské lekárske listy, 2014
Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of... more Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of both drugs is associated with increased risk of gastrointestinal (GI) bleeding. The administration of drugs inhibiting gastric acid production represents an effective way to avoid GI disorders associated with antiplatelet therapy. Objectives: The aim of our study was to evaluate the use of gastroprotective medication in elderly antiplatelet users in relation to risk factors for GI bleeding. Methods: Patients (n = 428) aged ≥ 65 years who were prescribed low dose ASA or clopidogrel in monotherapy or combination at hospital discharge were enrolled in the study. Results: Only 39.7 % of patients with 2 or more risk factors for GI bleeding were prescribed gastroprotective medication at hospital discharge. The probability of elderly antiplatelet drug user for prescription of gastroprotective medication was improved with following risk factors: age ≥ 85 years (OR = 2.99); history of peptic ulcer disease/ GI bleeding (OR = 15.79); other GI disorders (OR = 15.48); concomitant therapy with drugs increasing the risk of GI bleeding-systemic corticosteroids (OR = 29.03) and NSAIDs (OR = 4.79). Conclusion: Results of our study indicate the necessity to increase the awareness of GI bleeding risk in longterm antiplatelet users among prescribing physicians (Tab.
International Journal of Clinical Pharmacy
Phytotherapy Research, 2016
The progression of diabetes mellitus leads in time to the development of serious cardiovascular c... more The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy.
Farmaceutický obzor
Anthracyclines are substances used in the therapy of several kinds of cancer. Their usage is limi... more Anthracyclines are substances used in the therapy of several kinds of cancer. Their usage is limited by serious side effects affecting myocardium and endothelial cells. Natural substances may protect cells from oxidative stress. The aim of our study was to evaluate the effects of natural compounds with potential antioxidative properties on experimental endothelial dysfunction provoked by daunorubicin administration. Wistar rats were orally treated with Pycnogenol® (PYC) or infusions of Agrimonia eupatoria (AGR) and Cynara cardunculus (CYN) for two weeks. Single dose of daunorubicin (5mg/kg, i.v.) was applied into jugular vein under tribromoethanol anaesthesia. Control group received vehicle. All experiments were performed one hour after daunorubicin application. Contractions of isolated aorta were tested using norepinephrine and potassium chloride, relaxations were induced by acetylcholine. Medications with natural compounds prevented development of daunorubicin induced amelioration...
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2011
Pathology - Research and Practice, 2014
The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractio... more The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;in vitro&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.
Phytotherapy Research, 2009
The aim of this study was to describe the effects of Pycnogenol ® at various doses on preprandial... more The aim of this study was to describe the effects of Pycnogenol ® at various doses on preprandial and postprandial glucose levels, the levels of thiobarbituric acid reactive substances (TBARs) and N-acetyl-β β β β β-D-glucosaminidase (NAGA) and on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-induced diabetic rats. Pycnogenol ® treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8 weeks after induction of diabetes. Pycnogenol ® significantly decreased elevated levels of preprandial glycaemia in treated animals at all doses. At doses of 10 mg/kg b.w./day and 20 mg/kg b.w./day it significantly decreased elevated levels of postprandial glycaemia compared with diabetic non-treated animals. Pycnogenol ® failed to induce a significant decrease of postprandial glycaemia at a dose of 50 mg/kg b.w./day. Pycnogenol ® improved significantly the impaired MNCV at doses of 10 and 20 mg/kg b.w./day compared with non-treated animals. The levels of TBARs were elevated in diabetic rats. The levels of NAGA increased gradually despite the treatment. Pycnogenol ® failed to affect the increased levels of TBARs and NAGA. Pycnogenol ® lowered the elevated levels of glycaemia and reduced the decline in motor nerve conduction velocity in STZ-induced diabetic rats. The effect of Pycnogenol ® on postprandial glycaemic levels and MNCV was not dose-dependent.
Pathology - Research and Practice, 2012
Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by... more Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark -Pycnogenol ® (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p < 0.05) and significantly increased mean arterial blood pressure (by 19%; p < 0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p < 0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p < 0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p < 0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.
Phytotherapy Research, 2009
We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotoci... more We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotocininduced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91 phox -containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91 phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.
In order to reduce problems associated with potentially inappropriate medication prescribing in g... more In order to reduce problems associated with potentially inappropriate medication prescribing in geriatric patients, it´s necessary to establish appropriate regulatory measures and to increase training of medical doctors and pharmacists in problems of PIMs. Regulatory measures regarding PIM use widely differ across Europe. The aim of this study was to investigate what prescription limits are established for EU-7 PIMs in Central and Eastern European countries. To avoid ageism and ageist practices in inappropriate medication use in older patients, prescription limits for PIMs should be harmonized across Europe.
Poskodenie ciev predstavuje najcastejsiu komplikaciu diabetes mellitus (DM). Terapia DM sa preto ... more Poskodenie ciev predstavuje najcastejsiu komplikaciu diabetes mellitus (DM). Terapia DM sa preto orientuje nielen na upravu hodnot glykemie, ale aj na prevenciu a liecbu cievneho poskodenia. Niektore skupiny v sucasnosti použivaných antidiabetik maju endotelovoprotektivne vlastnosti, ktore nie su iba dosledkom ich ucinku na hladinu glykemie. Su perspektivnymi nastrojmi pre znižovanie kardiovaskularnej morbidity a mortality u diabetikov. Predložena praca sa zaobera jednotlivými skupinami antidiabetik z hľadiska ich vplyvu na endotelovu dysfunkciu u pacientov s DM 2. typu.
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2013
We observed the changes in electrical activity, biometric and haemodynamic parameters of hearts i... more 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...
Bratislava Medical Journal, 2014
Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of... more Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of both drugs is associated with increased risk of gastrointestinal (GI) bleeding. The administration of drugs inhibiting gastric acid production represents an effective way to avoid GI disorders associated with antiplatelet therapy. Objectives: The aim of our study was to evaluate the use of gastroprotective medication in elderly antiplatelet users in relation to risk factors for GI bleeding. Methods: Patients (n = 428) aged ≥ 65 years who were prescribed low dose ASA or clopidogrel in monotherapy or combination at hospital discharge were enrolled in the study. Results: Only 39.7 % of patients with 2 or more risk factors for GI bleeding were prescribed gastroprotective medication at hospital discharge. The probability of elderly antiplatelet drug user for prescription of gastroprotective medication was improved with following risk factors: age ≥ 85 years (OR = 2.99); history of peptic ulcer disease/ GI bleeding (OR = 15.79); other GI disorders (OR = 15.48); concomitant therapy with drugs increasing the risk of GI bleeding-systemic corticosteroids (OR = 29.03) and NSAIDs (OR = 4.79). Conclusion: Results of our study indicate the necessity to increase the awareness of GI bleeding risk in longterm antiplatelet users among prescribing physicians (Tab.
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2013
The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its abilit... more The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its ability to improve endothelial dysfunction in diabetic animals. The aim of this study was to isolate from Pycnogenol® mixture its active compounds and compare their efficacy on observed parameters. Pycnogenol® mixture was fractioned by re-extracting with petroleum ether, chloroform, ethyl acetate and butanol, subsequently. Pycnogenol® mixture and fractions (butanolic, water, ethyl acetate) were administered during 6 weeks to diabetic rats. Blood glucose levels were assessed from the arterio-venous blood at the beginning of experiment and at the end of experiment. Endothelial dysfunction was evaluated as the contractile responses to phenylephrine and acetylcholine. The amount of collagen I and III was assessed from thoracic aorta after picrosirius red staining. For the confirmation of the changes on molecular level, we determinated endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90...
Phytotherapy Research, 2009
We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin... more We studied whether Pycnogenol® (PYC) may attenuate the development of experimental streptozotocin‐induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)‐producing molecules (gp91phox‐containing NADPH oxidase and NO‐signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha‐tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect ...
Pathology - Research and Practice, 2012
Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by... more Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark - Pycnogenol(®) (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and significantly increased mean arterial blood pressure (by 19%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.
Bratislavské lekárske listy, 2014
Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of... more Background: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy or combination of both drugs is associated with increased risk of gastrointestinal (GI) bleeding. The administration of drugs inhibiting gastric acid production represents an effective way to avoid GI disorders associated with antiplatelet therapy. Objectives: The aim of our study was to evaluate the use of gastroprotective medication in elderly antiplatelet users in relation to risk factors for GI bleeding. Methods: Patients (n = 428) aged ≥ 65 years who were prescribed low dose ASA or clopidogrel in monotherapy or combination at hospital discharge were enrolled in the study. Results: Only 39.7 % of patients with 2 or more risk factors for GI bleeding were prescribed gastroprotective medication at hospital discharge. The probability of elderly antiplatelet drug user for prescription of gastroprotective medication was improved with following risk factors: age ≥ 85 years (OR = 2.99); history of peptic ulcer disease/ GI bleeding (OR = 15.79); other GI disorders (OR = 15.48); concomitant therapy with drugs increasing the risk of GI bleeding-systemic corticosteroids (OR = 29.03) and NSAIDs (OR = 4.79). Conclusion: Results of our study indicate the necessity to increase the awareness of GI bleeding risk in longterm antiplatelet users among prescribing physicians (Tab.
International Journal of Clinical Pharmacy
Phytotherapy Research, 2016
The progression of diabetes mellitus leads in time to the development of serious cardiovascular c... more The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy.
Farmaceutický obzor
Anthracyclines are substances used in the therapy of several kinds of cancer. Their usage is limi... more Anthracyclines are substances used in the therapy of several kinds of cancer. Their usage is limited by serious side effects affecting myocardium and endothelial cells. Natural substances may protect cells from oxidative stress. The aim of our study was to evaluate the effects of natural compounds with potential antioxidative properties on experimental endothelial dysfunction provoked by daunorubicin administration. Wistar rats were orally treated with Pycnogenol® (PYC) or infusions of Agrimonia eupatoria (AGR) and Cynara cardunculus (CYN) for two weeks. Single dose of daunorubicin (5mg/kg, i.v.) was applied into jugular vein under tribromoethanol anaesthesia. Control group received vehicle. All experiments were performed one hour after daunorubicin application. Contractions of isolated aorta were tested using norepinephrine and potassium chloride, relaxations were induced by acetylcholine. Medications with natural compounds prevented development of daunorubicin induced amelioration...
Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2011
Pathology - Research and Practice, 2014
The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractio... more The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;in vitro&amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.
Phytotherapy Research, 2009
The aim of this study was to describe the effects of Pycnogenol ® at various doses on preprandial... more The aim of this study was to describe the effects of Pycnogenol ® at various doses on preprandial and postprandial glucose levels, the levels of thiobarbituric acid reactive substances (TBARs) and N-acetyl-β β β β β-D-glucosaminidase (NAGA) and on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-induced diabetic rats. Pycnogenol ® treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8 weeks after induction of diabetes. Pycnogenol ® significantly decreased elevated levels of preprandial glycaemia in treated animals at all doses. At doses of 10 mg/kg b.w./day and 20 mg/kg b.w./day it significantly decreased elevated levels of postprandial glycaemia compared with diabetic non-treated animals. Pycnogenol ® failed to induce a significant decrease of postprandial glycaemia at a dose of 50 mg/kg b.w./day. Pycnogenol ® improved significantly the impaired MNCV at doses of 10 and 20 mg/kg b.w./day compared with non-treated animals. The levels of TBARs were elevated in diabetic rats. The levels of NAGA increased gradually despite the treatment. Pycnogenol ® failed to affect the increased levels of TBARs and NAGA. Pycnogenol ® lowered the elevated levels of glycaemia and reduced the decline in motor nerve conduction velocity in STZ-induced diabetic rats. The effect of Pycnogenol ® on postprandial glycaemic levels and MNCV was not dose-dependent.
Pathology - Research and Practice, 2012
Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by... more Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark -Pycnogenol ® (PYC) with hypoglycaemic and antioxidant properties in 8-9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50 mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p < 0.05) and significantly increased mean arterial blood pressure (by 19%; p < 0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p < 0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p < 0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p < 0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.
Phytotherapy Research, 2009
We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotoci... more We studied whether Pycnogenol ® (PYC) may attenuate the development of experimental streptozotocininduced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91 phox -containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91 phox (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.