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Marian Tomasiak

Publications and source records attributed to Marian Tomasiak.

14 recordsLinked to original sources
PubMed2006

Peroxynitrite can affect platelet responses by inhibiting energy production.

Peroxynitrite (ONOO-) strongly inhibits agonist-induced platelet responses. However, the mechanisms involved are not completely defined. Using porcine platelets, we tested the hypothesis that ONOO- reduces platelet aggregation and dense granule secretion by inhibiting energy production. It was found that ONOO- (25-300 microM) inhibited collagen-induced dense granule secretion (IC50 = 55 +/- 7 microM) more strongly than aggregation (IC(50) = 124 +/- 16 microM). The antiaggregatory and antisecretory effects of ONOO- were only slightly (5-10%) reduced by 1H-[1,2,4]-oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. In resting platelets ONOO- (50-300 microM) enhanced glycolysis rate and reduced oxygen consumption, in a dose dependent manner. The ONOO- effects on glycolysis rate and oxygen consumption were not abolished by ODQ. The extent of glycolysis stimulation exerted by ONOO- was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or an uncoupler (2,4-dinitrophenol). Stimulation of platelets by collagen was associated with a rise in mitochondrial oxygen consumption, accelerated lactate production, and unchanged intracellular ATP content. In contrast to resting cells, in collagen-stimulated platelets, ONOO- (200 microM) distinctly decreased the cellular ATP content. The glycolytic activity and oxygen consumption of resting platelets were not affected by 8-bromoguanosine 3',5'-cyclic monophosphate. Blocking of the mitochondrial ATP production by antimycin A slightly reduced collagen-induced aggregation and strongly inhibited dense granule secretion. Treatment of platelets with ONOO- (50-300 microM) resulted in decreased activities of NADH : ubiquinone oxidoreductase, succinate dehydrogenase and cytochrome oxidase. It is concluded that the inhibitory effect of ONOO- on platelet secretion and to a lesser extent on aggregation may be mediated, at least in part, by the reduction of mitochondrial energy production.

Animals↗
PubMed2005

The role of Na+/H+ exchanger in serotonin secretion from porcine blood platelets.

This study was undertaken to evaluate whether a link exists between the activation of protein kinase C (PKC), operation of Na(+)/H(+) exchanger (NHE), cell swelling and serotonin (5-HT) secretion in porcine platelets. Activation of platelets by thrombin or phorbol 12-myristate 13-acetate (PMA), a PKC activator, initiated a rapid rise in the activity of Na(+)/H(+) exchanger and secretion of 5-HT. Both thrombin- and PMA-evoked activation of Na(+)/H(+) exchanger was less pronounced in the presence of ethyl-isopropyl-amiloride (EIPA), an NHE inhibitor, and by GF 109203X, a PKC inhibitor. Monensin (simulating the action of NHE) caused a dose-dependent release of 5-HT that was not abolished by GF 109203X or EGTA. Lack of Na(+) in the suspending medium reduced thrombin-, PMA-, and monensin-evoked 5-HT secretion. GF 109203X nearly completely inhibited 5-HT release induced by PMA-, partly that induced by thrombin, and had no effect on 5-HT release induced by monensin. EIPA partly inhibited 5-HT release induced by thrombin and nearly totally that evoked by PMA. Electronic cell sizing measurements showed an increase in mean platelet volume upon treatment of cells with monensin, PMA or thrombin. The PMA- and thrombin-evoked rise in mean platelet volume was strongly reduced in the presence of EIPA. As judged by optical swelling assay monensin and PMA produced a rapid rise in platelet volume. The swelling elicited by PMA was inhibited by EIPA and its kinetics was similar to that observed in the presence of monensin. Hypoosmotically evoked platelet swelling did not affect platelet aggregation but significantly potentiated thrombin-evoked release of 5-HT and ATP. Taken together, these results show that in porcine platelets PKC may promote 5-HT secretion through the activation of NHE. It is hypothesized that enhanced Na(+)/H(+) antiport may result in a rise in cell membrane tension (due to cell swelling) which in turn facilitates fusion of secretory granules with the plasma membrane leading to 5-HT secretion.

Animals↗
PubMed2004

The effect of some epsilon-aminocaproic acid derivatives on platelet responses.

epsilon-Aminocaproic acid (EACA) is a synthetic low molecular drug with antifibrinolytic activity. However, treatment with this drug can be incidentally associated with an increased thrombotic tendency. The aim of the present work was to test synthetic EACA derivatives for their antiplatelet activities. We investigated the effect of three EACA derivatives with antifibrinolytic activity: I. epsilon-aminocaproyl-L-leucine hydrochloride (HCl*H-EACA-L-Leu-OH), II. epsilon-aminocaproyl-L-(S-benzyl)-cysteine hydrochloride (HCl*H-EACA-L-Cys(S-Bzl)-OH) and III. epsilon-aminocaproyl-L-norleucine (H-EACA-L-Nle-OH) on platelet responses (aggregation and adhesion) and on their integrity. It was found that: 1. as judged by LDH release test, none of the tested compounds, up to 20 mM, was toxic to platelets, 2. in comparison with EACA, all the synthetic derivatives inhibited much stronger the ADP- and collagen-induced aggregation of platelets suspended in plasma (platelet rich plasma) and aggregation of these cells in whole blood, 3. EACA and its derivatives exerted a similar inhibitory effect on the thrombin-induced adhesion of platelets to fibrinogen-coated surfaces. Since platelet activation and blood coagulation are tightly associated processes, the antiplatelet properties of EACA derivatives are expected to indicate reduced thrombotic properties of these derivatives compared to EACA.

Adenosine Diphosphate↗
PubMed2004

Involvement of Na+/H+ exchanger in desmopressin-induced platelet procoagulant response.

Desmopressin (DDAVP) action on platelets is associated with the development of procoagulant response but the underlying mechanism of this phenomenon is not known. We investigated whether this effect of DDAVP might be due to activation of plasma membrane Na+/H+ exchanger. The DDAVP-induced platelet procoagulant response, measured as phospholipid-dependent thrombin generation, was dose dependent and significantly weaker than that produced by collagen or monensin (mimics Na+/H+ antiport). Both the DDAVP- and collagen-produced procoagulant responses were less pronounced in the presence of EIPA, an Na+/H+ exchanger inhibitor. Flow cytometry studies revealed that in vitro treatment of platelets with DDAVP or collagen was associated with the appearance of both degranulated (and fragmented) and swollen cells. The DDAVP-evoked rise in size and granularity heterogeneity was similar to that produced by collagen or monensin and was not observed in the presence of EIPA. Using flow cytometry and annexin V-FITC as a probe for phosphatidylserine (PS) we demonstrated increased and uniform binding of this marker to all subsets of DDAVP-treated platelet population. The DDAVP-evoked PS expression was dose dependent, strongly reduced by EIPA and weaker than that caused by monensin or collagen. As judged by optical swelling assay, DDAVP in a dose dependent manner produced a rise in platelet volume. The swelling was inhibited by EIPA and its kinetics was similar to that observed in the presence of monensin. Electronic cell-sizing measurements showed an increase in mean platelet volume and a decrease in platelet count and platelet crit upon treatment with DDAVP. DDAVP elicited a slow (much slower than collagen) alkalinization of platelet cytosol. Altogether the data indicate an involvement of Na+/H+ exchanger in the generation of procoagulant activity in DDAVP-treated platelets.

Amiloride↗
PubMed2004

Nitric oxide and platelet energy metabolism.

This study was undertaken to determine whether nitric oxide (NO) can affect platelet responses through the inhibition of energy production. It was found that NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of glycolysis stimulation exerted by NO donors was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4-dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM) inhibited oxygen consumption by platelets. The effect of SNP and SNAP on glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase. SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and succinate dehydrogenase. Blocking of the mitochondrial energy production by antimycin A slightly affected collagen-evoked aggregation and strongly inhibited platelet secretion. The results indicate that: 1) in porcine platelets NO is able to diminish mitochondrial energy production through the inhibition of cytochrome oxidase, 2) the inhibitory effect of NO on platelet secretion (but not aggregation) can be attributed to the reduction of mitochondrial energy production.

Adenosine Diphosphate↗
PubMed2003

Platelet sodium-proton exchanger and phospholipid-dependent procoagulant activity in patients with type 2 diabetes.

Platelet Na(+)/H(+) exchanger (NHE) activity, phospholipid-dependent thrombin generation, and platelet factor 3 (PF3) availability were measured in 83 type 2 diabetics and in 40 age- and sex-matched healthy subjects. Na(+)/H(+) exchanger activity was significantly increased in diabetic patients in comparison to the controls (kappa = 4.29 +/- 0.71 x 10(-3) x s(-1) v 3.21 +/- 0.64 x 10(-3) x s(-1), P <.00001). However, there was no significant difference between subjects with (kappa = 4.28 +/- 0.75 x 10(-3) x s(-1)) and without (kappa = 4.26 +/- 0.32 x10(-3) x s(-1)) arterial hypertension, as well as between patients with normo- and microalbuminuria or overt proteinuria (kappa = 4.26 +/- 0.58 x 10(-3) x s(-1), kappa = 4.47 +/- 0.93 x 10(-3) x s(-1) and kappa = 4.07 +/- 0.38 x10(-3) x s(-1), respectively). Comparatively high NHE activity was observed in the group of patients with hemoglobin A(1c) (HbA(1c)) less than 7.5%. Multiple regression analysis revealed that the factors independently related to platelet Na(+)/H(+) exchanger activity were: total PF3 activity (beta = 0.77, P =.011) and triglyceride (TG) concentration (beta = 0.44, P =.039). Phospholipid-dependent thrombin generation and PF3 availability were also enhanced in all plasma fractions of diabetic patients, especially in platelet-poor plasma (PPP) and platelet-free plasma (PFP) (P <.0001 and P <.00001, respectively). There was a positive correlation between NHE activity and thrombin generation, as well as with PF3 availability in all plasma fractions. Our results suggest that enhanced platelet Na(+)/H(+) exchanger activity associated with raised phospholipid-dependent procoagulant activity may increase the risk of vascular damage in type 2 diabetic patients.

Adult↗
PubMed2003

[Nitric oxide in preterm labor].

Synthesis of nitric oxide proceeds in the human myometrium. Decrease of its concentrations can play an essential part in the initiation of uterine contractions in term. Authors suppose, that inhibition of the synthesis of nitric oxide plays a role in premature labour. Concentrations of nitric oxide in women with threatening premature labour were marked. Group I consisted of women with premature departure of amniotic fluid, group II--woman with retained amniotic fluid and with idiopathic contractile activity, group III--woman with departure of amniotic fluid and with idiopathic contractile activity. Concentration of nitric oxide was lower in the group of women with a premature contractile activity in comparison with healthy pregnant women in the same period of pregnancy. Higher concentrations of nitric oxide were observed in the group of patients without contractile activity after departure of amniotic fluid.

Adult↗
PubMed2003

[Morphologic parameters of blood platelets and activity NA+/H+ (NHE-1) exchanger in normal pregnancy and pregnancy complicated with preeclampsia].

UNLABELLED: The aim of the study was the evaluation of number and morphologic parameters of blood platelets and sodium-proton platelet exchangers in pregnant women in the 3rd trimester of pregnancy, healthy (155) and with preeclampsia (40). RESULTS: Blood platelet number was significantly lower in patients with preeclampsia than in healthy subjects (195,000 vs 222,000). Mean platelet volume was significantly higher in patients with preeclampsia (9.5 fl vs 8.6 fl). The activity of Na+/H+ was slightly higher in pregnants with preeclampsia.

Adult↗
PubMed2003

[Factors influencing platelet procoagulant activity in type II diabetic patients. The role of sodium-proton exchange].

The aim of our study was the estimation of platelet sodium-proton exchanger activity and platelet pro-coagulant activity, expressed as the availability of platelet factor 3 (PF3) and thrombin generation, in 83 type 2 diabetic patients (mean age 56.7 +/- 7.8 years) and 40 healthy subjects (mean age 54.4 +/- 6.2 years). Thrombin generation was measured in platelet rich plasma, using a chromogenic substrate S-2238. The availability of PF3 was estimated in platelet rich plasma, platelet poor plasma and platelet filtrated plasma, to assess procoagulant activity connected with platelets and cell derived microparticles, shedding upon activation (according to Jy and Horstman). The activity of platelet Na+/H+ exchanger was measured using an optical swelling assay. We found that the activity of PF3 and phospholipid dependent thrombin generation were significantly higher in diabetic patients, irrespective of their vascular complications and metabolic control. The highest increase of PF3 activity was observed in platelet poor (p < 0.0001) and platelet filtrated plasma (p < 0.000001). Na+/H+ exchange rate was significantly higher in diabetic patients in comparison to the controls (4.29 +/- 0.71 x 10(-3)/s vs 3.21 +/- 0.64 x 10(-3)/s, p < 0.00001). There was also a positive correlation between Na+/H+ exchanger activity and PF3 activity in all plasma fractions. Our results suggest that increased thrombin generation, enhanced platelet Na+/H+ exchanger activity and raised PF3 availability, connected mainly with cell derived microparticles, may enhance the risk of vascular damage in type 2 diabetic patients.

Adult↗
PubMed2002

The involvement of the Na(+)/H(+) exchanger in the formation of microvesicles by porcine platelets.

Activated platelets release microvesicles, which express procoagulant activity. The mechanism by which vesicles are formed is not entirely clear. This study was undertaken to determine whether a link exists between the operation of the plasma membrane Na(+)/H(+) exchanger (NHE) and vesiculation. It was found, that platelets treated with NHE-simulating monensin and the sodium influx-inducing gramicidin (without concomitant H+ efflux) produced vesicles demonstrating procoagulant activity. Alkalinization of platelet cytosol by NH4Cl failed to evoke vesicle release. Collagen and phorbol ester (PMA)-evoked vesiculation was diminished in the presence of 5-(N-ethyl-N-isopropyl amiloride) (EIPA, inhibitor of NHE) or GF 109203X (inhibitor of protein kinase C). Vesicle formation induced by collagen, PMA, and the calcium ionophore A23187 was less pronounced in the absence of external Na+. In comparison with collagen, thrombin was a stronger inducer of vesiculation. Platelets stimulated by thrombin, collagen, and PMA accumulated 22Na+, a phenomenon inhibited in the presence of EIPA. Collagen-evoked vesicle formation started with aggregation but culminated after its completion. The data indicate a significant contribution of the Na(+)/H(+) exchanger in the formation of microvesicles by porcine platelets.

Animals↗
PubMed2002

[Sodium-proton exchanges and platelet procoagulant activity in type 1 diabetic patients].

Platelet sodium-proton exchange rate and phospholipid dependent procoagulant activity were measured in 31 type 1 diabetics (mean age 32.3 +/- 10.1 years) and 35 healthy subjects (mean age 35.4 +/- 9.4 years). The activity of platelet Na+/H+ exchanger was measured in platelet rich plasma, using an optical swelling assay, according to Rosskopf et al. Platelet procoagulant activity was measured in platelet rich plasma, platelet poor plasma and platelet/microparticles filtrated plasma, using Russell's viper venom (according to Jy and Horstman) and calibrated with ship L-alpha-phosphatidylethanolamine. We found that Na+/H+ exchange rate was significantly higher in diabetic patients in comparison to the controls (p = 0.0009). There was also a positive correlation between the activity of Na+/H+ exchanger and phospholipid dependent procoagulant activity in all plasma fractions. We did not find a significant association between Na+/H+ exchanger activity and metabolic parameters studied, however in patients with HbA1c level > 7.5% higher Na+/H+ exchange rates were noted. Total procoagulant activity did not rise significantly in diabetic patients, but was markedly higher in platelet poor and platelet filtrated plasma. It was supposed that it originated from platelet derived microparticles, enriched in phospholipids. Our results suggest that an increased platelet Na+/H+ exchange rate and raised procoagulant activity connected with platelet microparticles may enhance the risk of vascular damage in type 1 diabetic patients.

Adult↗
PubMedDate not supplied

PST 2238 as an antihypertensive compound that antagonizes the effect of endogenous cardiac glycosides.

This review examines the role of endogenous cardiac glycosides (OLF--ouabain like factors) in the pathogenesis of hypertension. The discovery of ouabain as a new adrenal hormone affecting salt and water homeostasis has initiated research on a new group of compounds. OLF may provide new insights into the mechanisms and therapy of common cardiovascular diseases. PST 2238 (17beta-(3-furyl)-5beta-androstane-3beta-14beta-17alpha-triol), an antagonist of endogenous ouabain, might open new possibilities for the therapy of hypertension and congestive heart failure.

Androstanols↗
PubMedDate not supplied

Piracetam--an old drug with novel properties?

Piracetam (2-oxo-1-pyrrolidine-acetamide), the most common of the nootropic drugs, is a cyclic derivative of gamma-aminobutyric acid. The treatment with piracetam improves learning, memory, brain metabolism, and capacity. Piracetam has been shown to alter the physical properties of the plasma membrane by increasing its fluidity and by protecting the cell against hypoxia. It increases red cell deformability and normalizes aggregation of hyperactive platelets. Piracetam is an agent with antithrombotic, neuroprotective and rheological properties. The interaction of this molecule with the membrane phospholipids restores membrane fluidity and could explain the efficacy of piracetam in various disorders ranging from dementia and vertigo to myoclonus and stroke.

Alzheimer Disease↗