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P Kostka

Publications and source records attributed to P Kostka.

At least 19 recordsLinked to original sources

Physical and computer modelling of blood flow in a systemic-to-pulmonary shunt.

UNLABELLED: The aim of this work was the application of computer and physical in vitro simulation methods for estimating surgery procedure hemodynamics. The modified Blalock-Taussig (mB-T) palliative surgical procedure is performed to increase the pulmonary blood flow in children with congenital heart defects. Such a systemic-to-pulmonary shunt yields substantial modification in the blood flow within the large blood vessels. The objective of the present study was to investigate basic characteristics of the flow, flow pattern and pressure-flow efficiency, before and after opening of the mB-T graft. METHODS: The model was based on the vessel geometry obtained from the Visible Human Project and included the arch of aorta, the three arteries branching from the arch, the pulmonary trunck, and the left and right pulmonary arteries. The graft was added between the left subclavian artery and the left pulmonary artery. The glass model of the vessels was produced and investigated in a physical model of the cardiovascular system with an artificial ventricular device as the blood pump. Flow rate and hydrostatic pressure were measured at the inlet to and outlets from the glass model and in a few points within the system. Laser flow visualization was also performed. Computer simulations were done using the boundary conditions from the physical model. RESULTS: The opening of the mB-T graft changed flow distribution in all branches (including inflow). A complex flow pattern with large eddies and channelling of the flow in the vicinity of the graft and within it was observed in flow visualization and in computer simulations. Because of that complexity the local measurements of hydrostatic pressure at the vessel wall could not predict the average flow rate. The reversed flow in the graft was observed during the systole. CONCLUSIONS: The complex flow pattern developed in the physical model of the mB-T graft. The channelling of the flow and the formation of large eddies may yield high shear stress and modify blood properties. The rigid wall model can describe only some flow characteristics observed in vivo. Computer simulation is a very fast and accurate method which permits earlier qualification of cardiac surgeons on how to change cardiac vascular blood flow after operations.

Arteriovenous Shunt, Surgical↗

Robin Heart 2003--present state of the Polish telemanipulator project for cardiac surgery assistance.

The Polish telemanipulator (Robin Heart), for use in cardiac surgery, has been realized by the Foundation of Cardiac Surgery Development in Zabrze, Poland, in cooperation with specialists from the Technical University of Lodz and Warsaw University of Technology. The brief history of robotic surgery and fundamental advantages of employing robots in this field--safe, reliable and repeatable operative results with less patient pain, trauma and recovery time--follow the assumptions of the Polish Cardio-Robot project. The cardiac surgery robot, Robin Heart, is an original construction with a segment type structure which allows the various combination of its parts for different types of surgery. The telemanipulator for cardiac surgery will consist of two arms equipped with tools and one arm holding the camera. Several models suitable for surgeon contact systems, using the experience of centers designing the artificial hand and haptic systems have been worked out. The detailed mechanical analysis and original construction of main parts of the robot and development of the surgical planning system are presented in further sections.

Cardiac Surgical Procedures↗

Role of redox-active iron ions in the decomposition of S-nitrosocysteine in subcellular fractions of porcine aorta.

We recently reported that degradation of S-nitrosocysteine in homogenates of porcine aorta increased severalfold in the presence of Mg2+ ions [Kostka, P., Xu, B. & Skiles, E.H. (1999) J. Cardiovasc. Pharmacol. 33, 665-670]. The objective of the present study was to examine this in greater detail. The rate of S-nitrosocysteine degradation by aortic homogenates in the presence of Mg2+ ions exhibited differential sensitivity to chelators of iron ions. Terpyridine and diethylenetriamine penta-acetic acid (5-500 microM) caused a concentration-dependent inhibition of S-nitrosocysteine decay, whereas deferoxamine (100 microM) was ineffective. o-Phenanthroline (250 microM), a selective chelator of Fe2+ ions, potentiated the reaction at low initial concentrations of S-nitrosocysteine (< or = 15 microM) and inhibited the reaction at higher concentrations. The inhibitory effects of o-phenanthroline were related to suppression of S-nitrosocysteine decay by cysteine-mediated reduction of Fe3+. In the presence of o-phenanthroline, S-nitrosocysteine decomposition followed saturable kinetics with K0.5 = 3.8 +/- 0.3 microM and h = 1.8 +/- 0.1 (mean +/- SE, n = 4). Comparison of the rates of S-nitrosocysteine decay in different subcellular fractions showed selective association with the cytosolic fraction, as documented by copurification with lactate dehydrogenase activity. At non-limiting concentrations of S-nitrosocysteine, the rate of degradation in the cytosolic fraction was 4.1 +/- 0.3 nmol.min-1.(mg protein)-1 (n = 4). It is concluded that the cytosolic fraction of porcine aorta contains a protein factor, presumably an enzyme, capable of catalyzing heterolytic decomposition of the S-NO bond of S-nitrosocysteine in a process involving redox cycling of iron ions.

Animals↗

Formation of peroxynitrite during thiol-mediated reduction of sodium nitroprusside.

Aerobic incubations of equimolar concentrations (5-500 microM) of sodium nitroprusside (SNP) and dithiothreitol (DTT) carried out at pH 7.4 in the absence of light caused a concentration-dependent increase in the rates of oxidation of dihydrorhodamine-123. The enhancement of the rates of oxidation under such conditions was only partially sensitive to the inhibition by 100 mM dimethyl sulfoxide implying the involvement of both peroxynitrite and hydroxyl radicals in the observed effects. The oxidation of dihydrorhodamine-123 in the presence of SNP and DTT was nearly completely abolished by superoxide dismutase (20 U/ml). It was found that such an effect of the enzyme was related primarily to the stabilization of an intermediate of SNP reduction formed upstream to the liberation of nitrosonium ligand. Increased rates of oxidation of dihydrorhodamine-123 were also observed during the reduction of SNP with either L-cysteine or glutathione. It is concluded that thiol-mediated reduction of SNP under aerobic conditions is accompanied by the formation of oxygen-derived free radicals. Nitrosonium ligand liberated from the product(s) of SNP reduction is, under such conditions, converted to peroxynitrite.

Dithiothreitol↗

Degradation of S-nitrosocysteine in vascular tissue homogenates: role of divalent ions.

The objective of the study was to inquire about the mechanism(s) involved in the catabolism of S-nitrosothiols by vascular tissue under in vitro conditions. Incubations of S-nitrosocysteine (CYSNO) or S-nitrosoglutathione (GSNO) with homogenates isolated from porcine aortic smooth muscle resulted in only a marginal depletion of S-nitrosothiols from the reaction mixtures, which became statistically significant at relatively high concentrations of homogenate (> or =300 microg of protein/ml). Degradation of CYSNO (but not GSNO) was found to be potentiated several-fold by millimolar concentrations of either Mg2+ or Ca2+ ions. Under such conditions, the degradation of CYSNO was significantly suppressed by the removal of proteins by ultrafiltration (>80% inhibition) and eliminated completely by the alkylation of thiol groups with 1 mM N-ethylmaleimide. The potentiating effect of divalent ions on the degradation of CYSNO was insensitive to 0.1 mM neocuproine (selective chelator of Cu+ ions), although it was enhanced in the presence of 0.1 mM o-phenanthroline (selective chelator of Fe2+ ions). It is concluded that the degradation of CYSNO by tissue homogenate involves the interaction with protein-bound sulfhydryl groups, which is stimulated by Mg2+ or Ca2+ ions. The potentiating effect of o-phenanthroline suggests that the liberation of the nitrosonium moiety in such a process may be accompanied by its transfer to sulfur center(s) by transient formation of dinitrosyl-iron complexes.

Animals↗

Superoxide-mediated decomposition of biological S-nitrosothiols.

Incubation of S-nitrosocysteine or S-nitrosoglutathione (5-100 M) in the presence of a generator of superoxide (xanthine/xanthine oxidase) resulted in a time-dependent decomposition of S-nitrosothiols and accumulation of nitrite/nitrate in reaction mixtures. Quantitatively, the amounts of nitrite/nitrate represented >90% of nitrosonium equivalent of S-nitrosothiols degraded during the incubation. The reaction rates were unaffected by the presence catalase (1 unit/ml). Kinetic analysis showed that the degradation of S-nitrosothiols in the presence of superoxide proceeded at second order rate constants of 76,900 M-1 s-1 (S-nitrosocysteine) and 12,800 M-1 s-1 (S-nitrosoglutathione), respectively, with a stoichiometric ratio of 1 mol of S-nitrosothiol per 2 mol of superoxide. The findings provide the evidence for the involvement of superoxide in the metabolism of S-nitrosothiols. Furthermore, substantially slower reaction rates of superoxide with S-nitrosothiols relative to the reaction rate with NO are consistent with the contention that the transient formation of S-nitrosothiols in biological systems may protect NO from its rapid destruction by superoxide, thus enabling these compounds to serve as carriers or buffers of NO.

Catalase↗

Fluorometric detection of biological S-nitrosothiols.

A technique is presented for the quantitative detection of S-nitrosothiols formed by model biological thiols, cysteine, glutathione, and serum albumin. The technique is based on the detection of fluorescent compound 1-[H]-naphthotriazole formed between 2,3-diaminonaphthalene and nitrous acid released from S-nitrosothiols by treatment with mercuric chloride in an acidic environment. Concentration of S-nitrosothiols is determined from the difference in fluorescent signal (excitation/emission wavelengths of 363 nm/450 nm, respectively) observed in the presence and absence of 0.18 mM HgCl2. The yield of the reaction between 2,3-diaminonaphthalene and nitrous acid released from the S-NO bond by HgCl2 approaches 90-100% as documented by simultaneous assays of S-nitrosothiols by uv spectrophotometry and by Saville method. The assay can be applied to the analysis of mixtures containing excess of thiol and/or nitrite at neutral pH by pretreatment of samples with N-ethylmaleinimide and/or ammonium sulfamate, respectively. In analysis of S-nitrosothiols in protein-containing mixtures, HgCl2-mediated release of nitrous acid in the presence of 2,3-diaminonaphthalene is followed by neutralization of samples and precipitation of protein with 0.5 M 5-sulfosalicylic acid. The fluorometric assay is carried out at an excitation wavelength of 380 nm to eliminate the background fluorescence of 5-sulfosalicylic acid observed at lower wavelengths. The technique offers simple and rapid determination of S-nitrosothiols in complex reaction mixtures with the detection limit at low nanomolar concentrations.

2-Naphthylamine↗

[Facial eosinophilic granuloma. Healing with cryosurgical therapy].

A case of eosinophilic granuloma facial is presented in which the lesions have been successfully treated by cryotherapy, healing with slight pigmentation. Since this disease appears to be difficult to treat, a great many forms of therapy have been proposed in the literature. These will be discussed with the results presented.

Adult↗

Nitric oxide synthase in the autonomic nervous system of canine ileum.

The synaptosomes from canine ileal deep muscular plexus possess a nitric oxide (NO)-sensitive soluble guanylate cyclase, as demonstrated by approximately 3- to 4-fold elevation of synaptosomal cyclic GMP levels in the presence of either 1 mM sodium nitroprusside or L-arginine (20-1,000 microM) plus 1 mM NADPH. The activating effect of L-arginine on synaptosomal soluble guanylate cyclase was related to its enzymatic conversion to citrulline by NO synthase. The synaptosomal NO synthase was found to exhibit both calcium-independent and calcium/calmodulin-dependent components accounting for approximately 2- to 2.5-fold and 7- to 8-fold increases in the basal activity, respectively. The absolute magnitude of these activities was several-fold greater compared to the activities observed in the isolated cells of circular smooth muscle. The synaptosomal Ca-independent and Ca/calmodulin-dependent NO synthase activities were inhibited by methylene blue and L-NG-arginine methyl ester. The NO synthase activity was also attenuated in the presence of cyclic AMP (10 microM). Such an inhibition was related primarily to the suppression of Ca-independent activity. The ability of enteric nerves to generate NO from L-arginine strongly suggests the involvement of this process in the biochemical mechanisms underlying the neurogenic control of intestinal motility.

Amino Acid Oxidoreductases↗

[The Budapest agglomeration, 1980-1990].

"The study analyses the development of Budapest and [the] 6 towns and 37 communes forming its conurbation between 1980 and 1990." Consideration is given to the city's population dynamics; housing conditions, including availability of utilities, transportation, telecommunications, and retail stores; health conditions of the population; and educational opportunities for residents. (SUMMARY IN ENG AND RUS)

Communication↗

Prejunctional muscarinic receptors in the deep muscular plexus of canine ileum: comparison with smooth muscle receptors.

Prejunctional muscarinic receptors from the deep muscular plexus of canine ileum were studied, and their properties were compared with those of the postjunctional receptors of the circular smooth muscle. In the purified synaptosomal fraction (a fraction containing primarily the axonal varicosities of deep muscular plexus), the muscarinic ligand N-[3H]methylscopolamine labeled an apparently homogenous population of receptors (nH = 1) with a Kd of 2.7 nM and a Bmax of 195 +/- 44 fmol/mg protein (mean +/- S.D., n = 4). These receptors showed a high affinity for the M3/M1-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (pKi = 7.41); in contrast, the pKi values of pirenzepine (5.60), methoctramine (5.65) and AF-DX 116 (5.21) implied little selectivity for these subtypes. The binding properties of muscarinic receptors in the synaptosomal fraction were different from the binding properties of muscarinic receptors in the purified circular smooth muscle plasma membranes. Most notably, the circular smooth muscle receptors had significantly lower affinity for N-[3H]methylscopolamine (Kd = 16 nM) with a Bmax value of 2088 +/- 276 fmol/mg. The affinities of the M2 subtype-selective muscarinic antagonists methoctramine and AF-DX 116 were similar in both membrane preparations. The receptor population associated with the deep muscular plexus synaptosomal fraction was linked to the inhibition of adenylate cyclase activity, as demonstrated by a concentration-dependent, atropine-sensitive inhibition of the forskolin-stimulated enzyme in the presence of muscarinic agonists carbachol and oxotremorine. Based on the pharmacological observations presented here, the prejunctional muscarinic receptors in the axonal varicosities of deep muscular plexus are different from the postjunctional receptors present in the circular smooth muscle.

Adenylyl Cyclases↗

Identification and characterization of high-affinity Ca2(+)-ATPase associated with axonal plasma membranes of dog mesenteric nerves.

The microsomal fraction isolated from dog mesenteric nerve fibres was found to contain ATPase activity stimulated by micromolar concentrations of Ca ions. Such a high-affinity Ca2(+)-ATPase (hereafter referred to as HA Ca-ATPase) followed a Michaelis-Menten kinetics with Km for Ca ions of 0.4 microM and Vmax = 12.5 +/- 2.4 mumol Pi.mg-1h-1. The examination of the subcellular origin of HA Ca-ATPase revealed that this enzyme is associated with axonal plasma membranes as documented by its co-purification with several plasma membrane marker enzymes and with tetrodotoxin-sensitive 3H-saxitoxin binding. The addition of exogenous magnesium ions (Mg) resulted in a non-competitive inhibition of HA Ca-ATPase with Ki = 0.5 mM. The reaction velocity of HA Ca-ATPase was also inhibited by other divalent ions with the order of potency Mg greater than Mn greater than Zn greater than or equal to Co greater than Ni. In contrast to low affinity (high Km) Mg- and Ca-ATPase, the HA Ca-ATPase was insensitive to the inhibition by sodium azide (10 mM) and sodium fluoride (10 mM). Similarly, the specific activity of HA Ca-ATPase was unaffected by vanadate (100 microM) and N-ethylmaleinimide (100 microM). It is concluded that axonal plasma membranes of dog mesenteric nerves contain HA Ca-ATPase which seems to be unrelated to calcium-transporting Mg-dependent, Ca-stimulated ATPase.

Animals↗

Presynaptic and postjunctional muscarinic receptors in dog ileum: binding studies.

[3H]N-Methylscopolamine identified two distinct populations of muscarinic receptors in membranes derived from the longitudinal smooth muscle/myenteric plexus of dog ileum. In isolated axonal varicosities, the half-maximal saturation of binding sites occurred at 2.38 +/- 0.39 nM [3H]N-methylscopolamine, with maximal binding capacity 140 +/- 35 fmol/mg protein (mean +/- S.D., n = 8). In purified smooth muscle plasma membranes, the Kd value was 16 +/- 3 nM with Bmax 1960 +/- 494 fmol/mg. The displacement potencies of subtype-selective muscarinic antagonists in the fraction of axonal varicosities followed the order 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methiodide much greater than pirenzepine = methoctramine greater than AF-DX 116 with pKi values 7.38, 5.67, 5.70 and 5.13, respectively. Both 4-DAMP methiodide and pirenzepine were approximately 4-fold less potent in displacing the ligand from the receptors in smooth muscle plasma membranes as compared to varicose receptors. The potency ratios of cardioselective antagonists methoctramine and AF-DX 116 on varicose and smooth muscle receptors were 1 and 1.7. It is concluded that presynaptic receptors located on isolated axonal varicosities have pharmacological properties similar to glandular (M3) subtype of muscarinic receptors. The binding properties of receptors present in smooth muscle plasma membranes were found incompatible with those of any of the M1, M2 or M3 subtypes.

Animals↗

Distribution of opioid receptors in canine small intestine: implications for function.

Distribution of the binding sites for [3H]diprenorphine, a non-selective opiate ligand, was studied in membrane fractions from longitudinal muscle/myenteric plexus and circular muscle containing deep muscular plexus. [3H]saxitoxin was used as a marker for neuronal plasma membranes and 5'-nucleotidase as a marker for smooth muscle plasma membranes. Saxitoxin binding correlated strongly with diprenorphine binding, but 5'-nucleotidase correlated poorly with diprenorphine or saxitoxin binding in these fractions. Opiate binding sites in membranes of myenteric and deep muscular plexus were of high affinity (Kd = 0.12 and 0.18 nM, respectively) with maximum binding capacity of 400 and 500 fmol/mg protein, respectively. Competition experiments using subtype-selective opiate ligands indicated that all three subtypes of opiate receptors were present in the same ratio of 40-45% mu-subtypes, 40-45% delta-subtypes, and 10-15% kappa-subtypes on both plexuses. Opiate receptors of canine small intestine, therefore, are located primarily or exclusively on nerves with similar distributions in nerve membranes containing only axonal varicosities (deep muscular plexus) as in those containing neurons, dendrites, and varicosities (myenteric plexus).

Animals↗

Identification and characterization of presynaptic and postsynaptic beta adrenoreceptors in the longitudinal smooth muscle/myenteric plexus of dog ileum.

The subcellular distribution of [125I]cyanopindolol (125I-CYP) binding in membrane fractions derived from the longitudinal smooth muscle/myenteric plexus (LSM/MP) of dog ileum followed a bimodal pattern with selective enrichments in the purified synaptosomal (S2) fraction and the purified smooth muscle plasma membrane (M2) fraction. The half-maximal saturation of binding sites in both fractions occurred at 10 pM [125I]CYP with maximal binding capacities, in femtomoles per milligram of protein, 70 +/- 10 (S2 fraction) and 110 +/- 25 (M2 fraction). Approximately 80% of binding sites in either membrane fraction exhibited a high affinity for beta-2 selective antagonist ICI 118,551 (Ki = 1.4 +/- 0.4 nM in S2 and 1.8 +/- 0.6 nM in M2; mean +/- S.D. n = 3), whereas remaining 20% of binding sites had a low affinity for this agent (Ki = 2.6 +/- 1.5 microM in S2 and 0.55 +/- 0.2 microM in M2). The beta-1-selective antagonist ICI 89,406 had a high affinity for approximately 20% of binding sites (Ki = 12 +/- 7 nM in S2 and 4 +/- 2 nM in M2) and a low affinity for approximately 80% of binding sites (Ki = 0.34 +/- 0.16 microM in S2 and 0.42 +/- 0.24 microM in M2). The displacement potencies of beta-adrenergic agonists followed the order (-)-isoproterenol greater than salbutamol (-)-epinephrine greater than (-)-norepinephrine in each membrane preparation. The inclusion of 0.1 mM 5'-guanylylimidodiphosphate into assay medium resulted in a decreased affinity of receptors for agonists and increased values of Hill coefficients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗