T. Malinski - Academia.edu (original) (raw)
Papers by T. Malinski
Thrombosis and haemostasis, 1997
ABSTRACT
European Heart Journal
Background Atherosclerotic plaques can elaborate reactive oxygen species (ROS) that reduce nitric... more Background Atherosclerotic plaques can elaborate reactive oxygen species (ROS) that reduce nitric oxide (NO) bioavailability. Cellular detoxification enzymes including various peroxiredoxin (PRDX) and superoxide dismutase (SOD) isoforms can inactivate ROS. The omega-3 fatty acid (n3-FA) eicosapentaenoic acid (EPA) reduced cardiovascular (CV) events in high-risk patients (REDUCE-IT), a benefit not observed with mixed n3-FAs containing docosahexaenoic acid (DHA). Purpose The purpose of this study was to compare the effects of EPA and DHA on NO bioavailability and expression of detoxification enzymes in the vascular endothelium in vitro. Methods Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA or DHA at equimolar levels (10 μM) for 2 h, then challenged with IL-6 at 12 ng/ml for 24 h. Proteomic analysis was performed using LC/MS to measure relative protein expression. Only significant (p<0.05) changes between treatment groups >1-fold were analyzed. Cells we...
Postepy higieny i medycyny doswiadczalnej, 1999
European Surgery-Acta Chirurgica Austriaca
Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subse... more Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subsequent re-establishment of blood flow can result in ischaemia/reperfusion (I/R) injury. The consequences of such injury are local and remote tissue destruction. Methods: I/R is characterized by 'no reflow phenomenon' and interstitial oedema formation. Changes in the production of nitric oxide (NO) and superoxide play an important role in the development of I/R. Overproduction of reactive oxygenderived free radicals (OFR) leads to a consumption and depletion of endogenous scavenging antioxidants. Results: Direct NO measurements showed a production of large concentrations of NO from cNOS at the beginning of ischaemia. Intracellular influx of Ca 2+ after onset of ischaemia activates cNOS, leading to local depletion of L-arginine and subsequently to disarrangement of cNOS, which produces superoxide instead of NO. Microvascular constriction during 'no fellow' reflects deficiency in vasodilator NO due to its consumption by vasoconstrictor oxygen free radicals. Stimulated production of thromboxane A2 and endothelin release may also promote 'no reflow'. Conclusions: At least two major strategies are viable for preventing I/R injury: (a) treatment with L-arginine and their analogues, or BH4, thus preventing L-arginine and H4B deficient conditions, so that cNOS will not produce excessive 02-; (b) scavenging 02-already produced by cNOS and other potential sources of O2-by using large concentrations of free radical scavengers. Further research on oxidant/antioxidant biochemistry and its clinical application is needed.
Journal of Veterinary Pharmacology and Therapeutics
The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated ... more The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra® (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.5 mg/kg of afoxolaner and milbemycin oxime, respectively. The time to maximum afoxolaner plasma concentrations (tmax ) was 2-4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t1/2 ) and the oral bioavailability were 14 ± 3 days and 88.3% for afoxolaner, 1.6 ± 0.4 days and 80.5% for milbemycin oxime A3 and 3.3 ± 1.4 days and 65.1% for milbemycin oxime A4. The volume of distribution (Vd ) and systemic clearance (Cls) were determined following an IV dose of afoxolaner or milbemycin oxime. The Vd was 2.6 ± 0.6, 2.7 ± 0.4 and 2.6 ± 0.6 L/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The Cls was 5.0 ± 1.2, 75 ± 22 and 41 ± 12 mL/h/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The pharmacokinetic profile for the combination of afoxolaner and milbemycin oxime supports the rapid onset and a sustained efficacy for afoxolaner against ectoparasites and the known endoparasitic activity of milbemycin oxime.
Atherosclerosis Supplements, 2008
POSTER SESSIONS vention and therapy of vascular injury mediated by atorvastatin; iii) the atorvas... more POSTER SESSIONS vention and therapy of vascular injury mediated by atorvastatin; iii) the atorvastatin-mediated induction of HO-1 in response to a vascular injury. Methods: Balloon injury (BI) was used to induce IH in pig carotid arteries. Pigs were divided in 4 groups (n=7): normal diet; high-cholesterol diet; high-cholesterol diet + CO (250 ppm, intraoperatively); high-cholesterol diet + atorvastatin (80 mg/die). Morphometric and immunohistochemical analyses were performed on carotid sections; blood analyses (hemochrome, cholesterolemia, ELISA) were also performed. Results: The high-cholesterol diet exacerbated the development of IH respect to the normal diet. Atorvastatin and CO inhibited BI-induced restenosis of the carotid artery by enhancing HO-1 expression. Both atorvastatin and CO reduced the leukocyte infiltrate in vascular lesions and reduced the systemic inflammatory state lowering the plasmatic concentration of proinflammatory cytokines and the number of circulating monocytes. Conclusions: This study demonstrates that: i) a high-cholesterol diet induces a persistent state of vascular low-grade inflammation that worsen the vascular response following BI; ii) atorvastatin and CO have a protective role in the pathogenesis and outcome of inflammatory response following vascular injury; iii) atorvastatin prevents IH inducing HO-1 expression in the vascular wall.
Annals of clinical and laboratory science
Nitric oxide is generated from L-arginine by the action of nitric oxide synthase, an enzyme encod... more Nitric oxide is generated from L-arginine by the action of nitric oxide synthase, an enzyme encoded by three different genes. Nitric oxide is involved in an expanding number of phenomena. This involvement may be documented by direct detection using spectrophotometric or electrochemical methods or more often by indirect methods. Indirect methods for detection of nitric oxide effects include localization of nitric oxide synthase enzyme by immunochemistry or messenger ribonucleic acid (mRNA) by in situ hybridization, bioassays, inhibition of nitric oxide synthase activity, iron responsive element binding protein activity, and production of nitrate/nitrite, L-citrulline, or cyclic guanosine monophosphate (cGMP). Careful evaluation of potential pitfalls associated with these indirect methods of detecting nitric oxide effects prior to their use will prevent misinterpretation of results.
Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 1985
Abstract Neutralization of the positive charge of the pyridinium cation (Pyr + ) ads adsorbed at ... more Abstract Neutralization of the positive charge of the pyridinium cation (Pyr + ) ads adsorbed at the mercury/water interface following electrochemical reduction is likely to provoke a very fast flat-to-perpendicular reorientation of the adsorbed species, thus rendering the perpendicularly adsorbed radical (Pyr ) ads electrochemically inactive. Therefore, it cannot be ascertained by means of cyclic voltammetry whether dimerization of the (Pyr ) ads radicals, which occurs in solution, also occurs at the mercury/water interface.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2015
Clinical trials have shown that atorvastatin benefits patients with diabetes even with normal bas... more Clinical trials have shown that atorvastatin benefits patients with diabetes even with normal baseline LDL levels. We hypothesized that atorvastatin improves endothelial cell (EC) function and reduces inflammation in hypertensive rats with diabetes. Non-diabetic and streptozotocin-induced type 2 diabetic male spontaneously hypertensive rats (SHR) were treated with atorvastatin at 20 mg/kg/day. After five weeks, nitric oxide (NO) and peroxynitrite (ONOO(-)) were measured in aortic and glomerular endothelial cells. A tandem of nanosensors was used to simultaneously measure NO and ONOO(-) concentration and their ratio [NO]/[ONOO(-)] was monitored with a time resolution better than 10 μs and detection limit 1 nM. [NO]/[ONOO(-)] was applied as a marker of endothelial NO synthase (eNOS) uncoupling, endothelial dysfunction and nitroxidative stress. Glucose, cholesterol, blood pressure (BP), and the cytokine RANTES were also measured. Diabetic SHR rats had elevated glucose (355 ± 38 mg/dL),...
Clinical chemistry, 2001
Excessive continuous NO release from inducible NO synthase over prolonged periods under pathologi... more Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions. We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats. An increase in diffusible NO generated by constitutive NO synthase was observed immedi...
Physiological research / Academia Scientiarum Bohemoslovaca, 1998
.NO concentration was measured in the periendothelial area of the femoral artery by Malinski&... more .NO concentration was measured in the periendothelial area of the femoral artery by Malinski's porphyrinic .NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 +/- 5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 micrograms/ml/min) or bradykinin (30-40 ng/ml/min) increased this value significantly to 204.3 +/- 16.4 and 266.5 +/- 16.4 nM (P < 0.01), respectively. Inhibition of .NO synthase by L-NAME (50 mg/kg) declined the basal .NO concentration only to 137.2 +/- 3.3 nM (P < 0.01). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in .NO concentration. Surprisingly, both agonists still induced a significant increase of .NO concentration by 125.3 +/- 8.3 and 156.6 +/- 26.9 nM, respectively (P < 0.01). One of the possible explanations may be that besides arginine-citrulline plus the .NO pathway other sources of .NO could be involved in the high level of .NO after .NO synthase blockade by L-NAME.
Annals of clinical and laboratory science
The change in transmembrane potential of rat adipocytes was measured using the fluorescent probe ... more The change in transmembrane potential of rat adipocytes was measured using the fluorescent probe 3,3'-diethylthiadicarbocyanine iodide, diS-C2-(5). The method was calibrated by altering the potassium ion concentration while keeping the sum of potassium and sodium ions at a constant concentration of 153 mM (Bailey et al: Bioelectrochem. Bioenergetics 21:333-42, 1989). Two insulin-mimetic agents, phospholipase C from Clostridium perfringens and concanavalin A, induced a dose dependent hyperpolarization of rat epididymal adipocytes, like insulin. Removal of endogenous adenosine with adenosine deaminase or adenosine receptor blockade with isobutylmethylxanthine following the initiation of insulin-induced hyperpolarization resulted in depolarization. These same agents induced hyperpolarization of -6 to -8 mV when added without insulin. The replacement of adenosine with its analogue, N6-phenylisopropyladenosine, plus insulin depolarized the cells toward the transmembrane potential est...
American Journal of Hypertension, 1997
Thrombosis and haemostasis, 1997
ABSTRACT
European Heart Journal
Background Atherosclerotic plaques can elaborate reactive oxygen species (ROS) that reduce nitric... more Background Atherosclerotic plaques can elaborate reactive oxygen species (ROS) that reduce nitric oxide (NO) bioavailability. Cellular detoxification enzymes including various peroxiredoxin (PRDX) and superoxide dismutase (SOD) isoforms can inactivate ROS. The omega-3 fatty acid (n3-FA) eicosapentaenoic acid (EPA) reduced cardiovascular (CV) events in high-risk patients (REDUCE-IT), a benefit not observed with mixed n3-FAs containing docosahexaenoic acid (DHA). Purpose The purpose of this study was to compare the effects of EPA and DHA on NO bioavailability and expression of detoxification enzymes in the vascular endothelium in vitro. Methods Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA or DHA at equimolar levels (10 μM) for 2 h, then challenged with IL-6 at 12 ng/ml for 24 h. Proteomic analysis was performed using LC/MS to measure relative protein expression. Only significant (p<0.05) changes between treatment groups >1-fold were analyzed. Cells we...
Postepy higieny i medycyny doswiadczalnej, 1999
European Surgery-Acta Chirurgica Austriaca
Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subse... more Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subsequent re-establishment of blood flow can result in ischaemia/reperfusion (I/R) injury. The consequences of such injury are local and remote tissue destruction. Methods: I/R is characterized by 'no reflow phenomenon' and interstitial oedema formation. Changes in the production of nitric oxide (NO) and superoxide play an important role in the development of I/R. Overproduction of reactive oxygenderived free radicals (OFR) leads to a consumption and depletion of endogenous scavenging antioxidants. Results: Direct NO measurements showed a production of large concentrations of NO from cNOS at the beginning of ischaemia. Intracellular influx of Ca 2+ after onset of ischaemia activates cNOS, leading to local depletion of L-arginine and subsequently to disarrangement of cNOS, which produces superoxide instead of NO. Microvascular constriction during 'no fellow' reflects deficiency in vasodilator NO due to its consumption by vasoconstrictor oxygen free radicals. Stimulated production of thromboxane A2 and endothelin release may also promote 'no reflow'. Conclusions: At least two major strategies are viable for preventing I/R injury: (a) treatment with L-arginine and their analogues, or BH4, thus preventing L-arginine and H4B deficient conditions, so that cNOS will not produce excessive 02-; (b) scavenging 02-already produced by cNOS and other potential sources of O2-by using large concentrations of free radical scavengers. Further research on oxidant/antioxidant biochemistry and its clinical application is needed.
Journal of Veterinary Pharmacology and Therapeutics
The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated ... more The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra® (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.5 mg/kg of afoxolaner and milbemycin oxime, respectively. The time to maximum afoxolaner plasma concentrations (tmax ) was 2-4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t1/2 ) and the oral bioavailability were 14 ± 3 days and 88.3% for afoxolaner, 1.6 ± 0.4 days and 80.5% for milbemycin oxime A3 and 3.3 ± 1.4 days and 65.1% for milbemycin oxime A4. The volume of distribution (Vd ) and systemic clearance (Cls) were determined following an IV dose of afoxolaner or milbemycin oxime. The Vd was 2.6 ± 0.6, 2.7 ± 0.4 and 2.6 ± 0.6 L/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The Cls was 5.0 ± 1.2, 75 ± 22 and 41 ± 12 mL/h/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The pharmacokinetic profile for the combination of afoxolaner and milbemycin oxime supports the rapid onset and a sustained efficacy for afoxolaner against ectoparasites and the known endoparasitic activity of milbemycin oxime.
Atherosclerosis Supplements, 2008
POSTER SESSIONS vention and therapy of vascular injury mediated by atorvastatin; iii) the atorvas... more POSTER SESSIONS vention and therapy of vascular injury mediated by atorvastatin; iii) the atorvastatin-mediated induction of HO-1 in response to a vascular injury. Methods: Balloon injury (BI) was used to induce IH in pig carotid arteries. Pigs were divided in 4 groups (n=7): normal diet; high-cholesterol diet; high-cholesterol diet + CO (250 ppm, intraoperatively); high-cholesterol diet + atorvastatin (80 mg/die). Morphometric and immunohistochemical analyses were performed on carotid sections; blood analyses (hemochrome, cholesterolemia, ELISA) were also performed. Results: The high-cholesterol diet exacerbated the development of IH respect to the normal diet. Atorvastatin and CO inhibited BI-induced restenosis of the carotid artery by enhancing HO-1 expression. Both atorvastatin and CO reduced the leukocyte infiltrate in vascular lesions and reduced the systemic inflammatory state lowering the plasmatic concentration of proinflammatory cytokines and the number of circulating monocytes. Conclusions: This study demonstrates that: i) a high-cholesterol diet induces a persistent state of vascular low-grade inflammation that worsen the vascular response following BI; ii) atorvastatin and CO have a protective role in the pathogenesis and outcome of inflammatory response following vascular injury; iii) atorvastatin prevents IH inducing HO-1 expression in the vascular wall.
Annals of clinical and laboratory science
Nitric oxide is generated from L-arginine by the action of nitric oxide synthase, an enzyme encod... more Nitric oxide is generated from L-arginine by the action of nitric oxide synthase, an enzyme encoded by three different genes. Nitric oxide is involved in an expanding number of phenomena. This involvement may be documented by direct detection using spectrophotometric or electrochemical methods or more often by indirect methods. Indirect methods for detection of nitric oxide effects include localization of nitric oxide synthase enzyme by immunochemistry or messenger ribonucleic acid (mRNA) by in situ hybridization, bioassays, inhibition of nitric oxide synthase activity, iron responsive element binding protein activity, and production of nitrate/nitrite, L-citrulline, or cyclic guanosine monophosphate (cGMP). Careful evaluation of potential pitfalls associated with these indirect methods of detecting nitric oxide effects prior to their use will prevent misinterpretation of results.
Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 1985
Abstract Neutralization of the positive charge of the pyridinium cation (Pyr + ) ads adsorbed at ... more Abstract Neutralization of the positive charge of the pyridinium cation (Pyr + ) ads adsorbed at the mercury/water interface following electrochemical reduction is likely to provoke a very fast flat-to-perpendicular reorientation of the adsorbed species, thus rendering the perpendicularly adsorbed radical (Pyr ) ads electrochemically inactive. Therefore, it cannot be ascertained by means of cyclic voltammetry whether dimerization of the (Pyr ) ads radicals, which occurs in solution, also occurs at the mercury/water interface.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2015
Clinical trials have shown that atorvastatin benefits patients with diabetes even with normal bas... more Clinical trials have shown that atorvastatin benefits patients with diabetes even with normal baseline LDL levels. We hypothesized that atorvastatin improves endothelial cell (EC) function and reduces inflammation in hypertensive rats with diabetes. Non-diabetic and streptozotocin-induced type 2 diabetic male spontaneously hypertensive rats (SHR) were treated with atorvastatin at 20 mg/kg/day. After five weeks, nitric oxide (NO) and peroxynitrite (ONOO(-)) were measured in aortic and glomerular endothelial cells. A tandem of nanosensors was used to simultaneously measure NO and ONOO(-) concentration and their ratio [NO]/[ONOO(-)] was monitored with a time resolution better than 10 μs and detection limit 1 nM. [NO]/[ONOO(-)] was applied as a marker of endothelial NO synthase (eNOS) uncoupling, endothelial dysfunction and nitroxidative stress. Glucose, cholesterol, blood pressure (BP), and the cytokine RANTES were also measured. Diabetic SHR rats had elevated glucose (355 ± 38 mg/dL),...
Clinical chemistry, 2001
Excessive continuous NO release from inducible NO synthase over prolonged periods under pathologi... more Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions. We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats. An increase in diffusible NO generated by constitutive NO synthase was observed immedi...
Physiological research / Academia Scientiarum Bohemoslovaca, 1998
.NO concentration was measured in the periendothelial area of the femoral artery by Malinski&... more .NO concentration was measured in the periendothelial area of the femoral artery by Malinski's porphyrinic .NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 +/- 5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 micrograms/ml/min) or bradykinin (30-40 ng/ml/min) increased this value significantly to 204.3 +/- 16.4 and 266.5 +/- 16.4 nM (P < 0.01), respectively. Inhibition of .NO synthase by L-NAME (50 mg/kg) declined the basal .NO concentration only to 137.2 +/- 3.3 nM (P < 0.01). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in .NO concentration. Surprisingly, both agonists still induced a significant increase of .NO concentration by 125.3 +/- 8.3 and 156.6 +/- 26.9 nM, respectively (P < 0.01). One of the possible explanations may be that besides arginine-citrulline plus the .NO pathway other sources of .NO could be involved in the high level of .NO after .NO synthase blockade by L-NAME.
Annals of clinical and laboratory science
The change in transmembrane potential of rat adipocytes was measured using the fluorescent probe ... more The change in transmembrane potential of rat adipocytes was measured using the fluorescent probe 3,3'-diethylthiadicarbocyanine iodide, diS-C2-(5). The method was calibrated by altering the potassium ion concentration while keeping the sum of potassium and sodium ions at a constant concentration of 153 mM (Bailey et al: Bioelectrochem. Bioenergetics 21:333-42, 1989). Two insulin-mimetic agents, phospholipase C from Clostridium perfringens and concanavalin A, induced a dose dependent hyperpolarization of rat epididymal adipocytes, like insulin. Removal of endogenous adenosine with adenosine deaminase or adenosine receptor blockade with isobutylmethylxanthine following the initiation of insulin-induced hyperpolarization resulted in depolarization. These same agents induced hyperpolarization of -6 to -8 mV when added without insulin. The replacement of adenosine with its analogue, N6-phenylisopropyladenosine, plus insulin depolarized the cells toward the transmembrane potential est...
American Journal of Hypertension, 1997