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Biomedical subjects

I Kanzik

Publications and source records attributed to I Kanzik.

At least 37 records · Page 2Linked to original sources
PubMed1998

Peroxynitrite: a putative cytotoxin.

In recent years it has become apparent that peroxynitrite, which is one of the toxic metabolites originating from the reaction of nitric oxide and superoxide presents a number of pathologic states in which free radicals are thought to be involved. Peroxynitrite is capable of oxidizing a wide variety of biomolecules including plasma, proteins, lipids, carbohydrates and nucleic acids. Peroxynitrite is involved in the hydroxylation of aromatic compounds and acts as a nitrating agent. It modifies free or protein-associated tyrosine residues to give nitrotyrosines, leaving a marker detectable in vivo. Peroxynitrite has been implicated in the pathophysiology of a variety of diseases including inflammation, atherosclerosis, arthritis, endotoxemia, ischaemia-reperfusion injury, or acute respiratory distress syndrome. Development of specific peroxynitrite scavengers may provide new approaches for the effective treatment of these disease states.

Animals↗
PubMed1997

The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approach to the management of graft spasm.

AIMS: We studied the effectiveness of levcromakalim, a potassium channel opener (KCO), in the prevention and reversal of spasm in arterial grafts used in coronary artery bypass operations, namely, internal mammary artery (IMA) and gastroepiploic artery (GEA). METHODS: Spasm was mimicked in vitro in arterial rings from 109 patients by increasing the vascular tension with noradrenaline, the thromboxane analogue U46619, endothelin-1 and K+. RESULTS: GEA displayed considerably higher contractile force to these agents than IMA. Pretreatment with levcromakalim depressed significantly the maximal contractile responses (either absolute or relative) to noradrenaline and U46619 but did not affect those of endothelin-1 and K+ in both of the arteries. Sensitivities (to all agents, except to endothelin-1) decreased significantly after levcromakalim. In experiments evaluating the antispasmodic activity of levcromakalim, a higher relaxant capacity was observed in GEA than IMA (for K+ contraction; IMA: 31.32 +/- 3.83%, n= 13 vs GEA: 98.01 +/- 0.71%, n=7, P<0.05). This different activity of levcromakalim between two arterial grafts was apparent even when GEA rings were contracted to higher force (g) than that of IMA (for K+ contraction; GEA: 72.56 +/- 4.96%, n = 7). Responses to levcromakalim were similar in IMA and GEA when endothelin-1 was used as the spasmogenic agent (IMA: 80.98 +/- 4.85%, n=10 vs GEA: 91.93 +/- 3.17%, n=7, P>0.05). CONCLUSIONS: Our results provide evidence that levcromakalim may have a therapeutic value in the treatment of spasm of coronary artery bypass grafts, especially GEA.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Antinociceptive effect of some amaryllidaceae plants in mice.

The antinociceptive effects of ethanolic extracts of Pancratium maritimum L., Narcissus tazetta subspecies tazetta and Leucojum aestivum L. bulbs have been investigated in mice using the p-benzoquinone-induced abdominal constriction and hot-plate tests. In the p-benzoquinone-induced abdominal constriction test the ethanolic extracts of P. maritimum (300, 600 or 1200 mg kg-1, s.c.) and N. tazetta subsp. tazetta (5, 50, 100 or 200 mg kg-1, s.c.) caused dose-dependent inhibition of abdominal constrictions whereas a fluctuating response was obtained from ethanolic extracts of L aestivum (2.5-500 mg kg-1, s.c.). In the hot-plate test P. maritimum and L. aestivum caused a significant increase of latency only at the highest concentrations used (1200 mg kg-1 and 500 mg kg-1, i.p., respectively). However, at these concentrations they also caused significant toxic effects. In contrast with P. maritimum and L. aestivum, N. tazetta subsp. tazetta (5-500 mg kg-1, i.p.) extracts had no antinociceptive effect in this test. These findings indicate that the antinociceptive effect of Amaryllidaceae plants differs depending on the model of nociception investigated.

Abdomen↗
PubMed1996

The comparison of vascular reactivities of arterial and venous grafts to vasodilators: management of graft spasm.

Graft spasm in the perioperative or postoperative period increases the risk of morbidity and mortality after coronary revascularization and hence necessitates urgent treatment. We have studied the effects of various vasodilators against noradrenaline- and endothelin-1-induced spasms in saphenous vein, internal mammary artery and gastroepiploic artery. In internal mammary and gastroepiploic arteries, the nitrovasodilators, sodium nitroprusside and glyceryl trinitrate, effectively reversed the spasms induced either with noradrenaline (for sodium nitroprusside; internal mammary artery: 101.07% +/- 1.63%; gastroepiploic artery: 94.10% +/- 2.07%) or endothelin-1 (for sodium nitroprusside; internal mammary artery: 97.67% +/- 4.94%; gastroepiploic artery: 90.69% +/- 2.61%). However, in saphenous vein contracted with endothelin-1, the responsiveness to nitrovasodilators was significantly blunted (for sodium nitroprusside: 52.33% +/- 5.19%) than that of rings contracted with noradrenaline (for sodium nitroprusside: 95.04% +/- 1.94%). Both arterial and venous grafts exhibited moderate beta-receptor function in response to isoproterenol. Isoproterenol was less effective in inhibiting the contractions of endothelin-1 in saphenous vein and gastroepiploic artery but not in internal mammary artery. On the other hand, nifedipine and papaverine were fully effective in reversing all the spasms in three of the graft materials. From these results, it can be deduced that saphenous vein is refractory against cyclic guanidine monophosphate (cGMP)-dependent and beta-receptor mediated relaxations when endothelin-1 was used as the spasmogenic agent. Internal mammary artery is the most responsive graft material to the vasodilators regardless of the nature of spasmogenic stimulus. Gastroepiploic artery exhibits functional similarity with internal mammary artery, with the exception of beta-receptor responsiveness.

Adult↗
PubMed1995

Effects of platelet-activating factor antagonists WEB 2086 and BN 50730 on digoxin-induced arrhythmias.

Effects of platelet-activating receptor antagonists WEB 2086 (1.0-30.0 mg.kg-1 intravenously) and BN 50730 (10.0 mg.kg-1 intravenously) alone or in combination with CGS 8515 (a specific 5-lipoxygenase inhibitor, 0.3 mg.kg-1 intravenously) and Dazmegrel (a thromboxane synthase inhibitor, 1.0 mg.kg-1.hr-1 intravenous infusion) on digoxin-induced arrhythmias were investigated in anaesthetised guinea-pigs. ECG, mean arterial blood pressure, heart rate and arrhythmias were recorded, starting 30 min. before digoxin administration and continuing for 60 min. afterwards. WEB 2086 (10.0 mg.kg-1 intravenously) reduced the mortality rate and arrhythmia score significantly compared to the control values. However, in combination with CGS 8515, it did not affect the mortality rate. BN 50730 (10.0 mg.kg-1) reduced the incidence of ventricular fibrillation and also arrhythmia score. BN 50730 in combination with Dazmegrel was reduced the arrhythmia score, incidence of ventricular fibrillation and mortality rate significantly, compared to control values. Digoxin-induced acute rise in mean arterial blood pressure was not affected by any of drug treatment except WEB 2086 (10.0 mg.kg-1) in combination with CGS 8515. Heart rate values did not differ between groups. However, pressure-rate index was reduced by WEB 2086 alone or in combination with CGS 8615. Results showed that although two different platelet-activating factor antagonists have different effects on the incidence of ventricular fibrillation and mortality, they improved the digoxin-induced arrhythmias when they were used either separately or in combination with CGS 8515 or Dazmegrel by implicating that platelet-activating factor has a role on digoxin-induced arrhythmias.

Animals↗
PubMed1994

Hypoglycaemic effect of Momordica charantia extracts in normoglycaemic or cyproheptadine-induced hyperglycaemic mice.

The hypoglycaemic effect of orally administered extracts of Momordica charantia L. fruits was examined in normoglycaemic or cyproheptadine-induced hyperglycaemic mice. The aqueous extract reduced the fasting glucose levels of hyperglycaemic or normoglycaemic mice. However, the ethanol extract did not affect the fasting or nonfasting glucose levels significantly in both groups of mice. There was no significant difference between the glucose-loaded and glucose-loaded plus aqueous extract given group. On the other hand, oral glucose-loading of the cyproheptadine-induced hyperglycaemic animals reduced the fasting glucose levels significantly. These results showed that aqueous extract of M. charantia fruits has a hypoglycaemic activity without improving the tolerance to glucose in cyproheptadine-induced diabetic mice.

Animals↗
PubMed1994

Endothelial function of human gastroepiploic artery in comparison with saphenous vein.

OBJECTIVE: Endothelial function is one of the important determinants of patency rate of a graft material used in coronary revascularisation. The aim of this study was to compare the endothelial reactivity of human gastroepiploic artery versus saphenous vein in response to various vasoactive substances. METHODS: Gastroepiploic artery and saphenous vein rings were mounted in an organ bath containing Krebs-Ringer bicarbonate solution aerated with 95% O2 and 5% CO2 at 37 degrees C. Endothelium dependent responses of acetylcholine, histamine, and bradykinin were examined on the precontracted rings of the vessels. The sensitivity of these two graft materials to the potent vasoconstrictor agent endothelin-1 was also compared. RESULTS: Acetylcholine, histamine, and bradykinin caused dose dependent relaxations in saphenous vein and gastroepiploic artery rings. These agonists were more effective in producing endothelium dependent relaxations in the artery than in the vein. Endothelium removal and pretreatment with nitro-arginine abolished the relaxations completely in saphenous vein but not in gastroepiploic artery, depending on the relaxing agent used. On the other hand, both graft materials showed nearly equal sensitivity to endothelin-1 (EC50 values; 3.5 x 10(-9) M in the vein versus 6.4 x 10(-9) M in the artery, p = NS) which was not affected by endothelium removal. CONCLUSIONS: Gastroepiploic artery exhibited more pronounced relaxation and a different response profile to endogenous vasoactive substances than saphenous vein. The demonstration of higher capacity of the artery to release vasoactive substances in response to various endogenous agents shows that gastroepiploic artery may have a better long term patency rate than saphenous vein.

Acetylcholine↗
PubMed1994

Nitric oxide production by human umbilical vessels in severe pre-eclampsia.

OBJECTIVE: Pre-eclampsia is characterized by an increased vascular tone which might be related to an abnormal endothelial cell function. As representatives of the fetal circulation, we compared the nitric oxide (NO)-releasing capacity of human umbilical vessels from normal and pre-eclamptic pregnancies. METHODS: Normal and pre-eclamptic umbilical vessels were mounted in parallel in an organ chamber with three perfusion lines superfusing the same detector tissue (rubbed rat aortic ring). In this cascade system the capacity of the umbilical vessels to release NO was measured under basal conditions and after stimulation with histamine, bradykinin or calcium ionophore A23187. RESULTS: Relaxations dependent on basal NO release were found to be significantly higher in pre-eclamptic vessels (especially in veins) than in normal vessels. Conversely, stimulated NO release in response to histamine or bradykinin was significantly decreased in pre-eclamptic umbilical arteries, but not in veins, compared with normal vessels. However, there was no significant difference in the release of NO in response to A23187 between normal and pre-eclamptic vessels. CONCLUSIONS: The NO-releasing and NO-producing capacity in the vessels from fetal circulation is not diminished in pre-eclampsia. However, in pre-eclamptic umbilical arteries the NO release in response to certain stimuli (histamine or bradykinin) is diminished, probably as a result of alterations in the receptor function.

Adult↗
PubMed1993

Epithelium-dependent responses of serotonin in a co-axial bioassay system.

Serotonin (10(-6) - 10(-4) M) produced relaxations in a concentration-dependent (at 10(-6) and 10(-5) M concentrations) manner followed by a contraction (at 10(-4) M concentration) in a co-axial system, which consisted of guinea-pig trachea as a donor organ for epithelial derived-relaxing factor(s) and phenylephrine-precontracted rat anococcygeus muscle as assay tissue. Serotonin produced a concentration-dependent contraction only in precontracted rat anococcygeus muscle mounted alone or mounted co-axially within epithelium-denuded trachea. Indomethacin (10(-6) M) significantly inhibited the initial relaxations (from 25.1 +/- 7.8 to 7.8 +/- 5.0% and from 35.6 +/- 8.7 to 10.4 +/- 8.3% at 10(-6) and 10(-5) M concentrations of serotonin), but did not affect the contraction. Imipramine (10(-8) M) and hydrocortisone (3 x 10(-5) M) reduced the initial relaxations (from 20.5 +/- 1.6 to 3.8 +/- 1.5% and from 32.1 +/- 6.4 to 18.9 +/- 3.9% at 10(-6) M and 10(-5) M concentrations of serotonin, respectively) and also converted the serotonin (10(-4) M)-induced contraction to a relaxation. In the co-axial system with trachea from guinea-pigs previously sensitized with i.p. injected egg-ovalbumin, the serotonin-induced biphasic response was converted to a contractile response only after ovalbumin challenge. Histopathologic changes were observed in the epithelium of challenged tracheas taken from sensitized guinea-pigs and alterations of serotonin-induced epithelium-dependent responses were attributed to the morphological and/or functional damage of tracheal epithelium caused by ovalbumin challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Antinociceptive effects of H1- and H2-antihistaminics in mice.

1. Two methods were used to study the analgesic effects of subcutaneous injections of antihistaminics in mice: the p-benzoquinone(PBQ)-writhing test and caudal compression test. 2. Mepyramine, lupitidine (SKF 93479), and famotidine produced significant antinociceptive effects dose-dependently, during both the PBQ-writhing and caudal compression tests. 3. However, ranitidine did not reveal any antinociceptive effect. 4. Icotidine (SKF 93319) produced significant antinociception and also augmented the analgesic effect of morphine, on the caudal compression test. 5. However, mepyramine, famotidine, and lupitidine did not affect morphine-induced analgesia on the caudal compression test and displayed a nonsignificant potentiation on morphine-induced analgesia in the PBQ-writhing test.

Analgesics↗
PubMed1992

Biphasic effect of histamine on spontaneously beating rat atria.

1. Effect of histamine (HA) (10(-4)-10(-2) M) on spontaneously beating rat atrium was investigated. HA produced a biphasic effect which is composed of an initial negative chronotropy followed by a positive chronotropic phase, at each single dose. 2. At a submaximal dose of HA (3 x 10(-3) M) we have investigated the effects of some antagonists on the biphasic effect profile. 3. Propranolol (10(-7) M) depressed the secondary phase by abolishing the biphasic pattern of the effect of HA leading it to a monophasic one (negative chronotropy). 4. On the other hand, combination with atropine (10(-7) M) was shown to reduce the negative inotropic effect (in the secondary phase) which was produced by HA in the presence of propranolol. 5. The initial negative chronotropic phase was significantly enhanced by propranolol and reduced by pheniramine (10(-6) M). 6. Pheniramine also potentiated the positive chronotropy at the secondary phase of the response, but cimetidine (10(-4) M) has no significant effect on both phases. 7. Theophylline (10(-4) M) abolished the initial negative chronotropic phase, but did not influence the secondary phase. Dipyridamole (10(-5) M) did not affect the secondary phase of the response of HA, but increased the initial negative chronotropic effect.

Animals↗
PubMed1989

Involvement of prostanoids in the pulmonary pressor effect of histamine.

The role of prostanoids in the pulmonary actions of histamine(HA) was investigated using various antagonists and assay organs in superfusion cascade. Intraarterial injection of HA to the perfused lung caused contractions of rabbit aorta, rat stomach strips, guinea pig trachea, but contraction followed by relaxation of bovine coronary artery, superfused with lung effluent. Lung effluent produced no significant changes in resting tensions of guinea pig ileum or rat colon. The thromboxane synthetase inhibitor, UK 38485, reduced and the thromboxane/prostaglandin receptor antagonist, SQ 29548 abolished HA-induced contractions of all superfused assay tissues. Both contractile and relaxant responses of bovine coronary artery were completely inhibited by indomethacin. The pulmonary pressor effect of HA was also significantly inhibited by all of these antagonists. Our results indicate that HA releases thromboxane A2, prostaglandin endoperoxides, and prostacyclin but not leukotriene and prostaglandin E2- like substances from the guinea pig lung.

Animals↗
PubMed1989

Temperature-dependent specific desensitization in the rat anococcygeus muscle to angiotensin II.

The effect of angiotensin II (A II) on isolated rat anococcygeus muscle was investigated. A II, when used submaximally (4 X 10(-9) mol/l), produced a rapid contraction of the rat anococcygeus muscle. However, a profound tachyphylaxis developed with repeated administrations. This tachyphylaxis is specific in nature, since the tissue responded normally to noradrenaline even after the establishment of a complete tachyphylaxis to the peptide. Incubation with phentolamine or indometacin had no effect on the A II-induced tachyphylaxis. On the other hand, a marked prevention of tachyphylaxis was obtained by lowering the bath temperature to 31 or 25 degrees C. These results indicate that neither noradrenaline nor prostaglandin release participate in the development of tachyphylaxis to A II in rat anococcygeus muscle, and this tachyphylaxis can be prevented by lowering the temperature of the bath solution.

Angiotensin II↗
PubMed1988

Effects of thromboxane synthetase inhibitor (UK 38,485) and thromboxane receptor antagonist (ICI 185,282) on digoxin-induced arrhythmias in anaesthetized guinea-pigs.

1. Increased local thromboxane (Tx) formation has been considered to be a contributing factor in digitalis-induced arrhythmias. 2. A potent Tx synthetase inhibitor (TxSI), UK 38,485 (0.1, 1.0 or 10.0 mg/kg per h, administered intravenously) and a Tx receptor antagonist (TxRA), ICI 185,282 (1, 2 or 10 mg/kg bolus and 1, 2 or 10 mg/kg per h, administered intravenously) were tested for their ability to reduce digoxin-induced arrhythmias in anaesthetized guinea-pigs. 3. Electrocardiograms, mean blood pressure, heart rate and arrhythmias were recorded, starting 30 min before digoxin administration and continued for 60 min afterwards. 4. ICI 185,282, at the doses used, significantly delayed the time of onset of arrhythmias, and reduced the incidence of ventricular fibrillation, mortality and arrhythmia score. In contrast, UK 38,485 was found to be effective on all measured variables only at the dose rate of 1.0 mg/kg per h, except for time required for the development of arrhythmias. These protective effects of both TxSI and TxRA were not found to be dose-dependent. 5. Arterial blood pressure and heart rate changes caused by either UK 38,485 or ICI 185,282 infusions did not have any marked effects on digoxin-induced arrhythmias. 6. These data suggest that endogenously released TxA2 and prostaglandin endoperoxides may play an important role in digoxin-induced arrhythmias in guinea-pigs.

Anesthesia↗
PubMed1987

Digoxin-induced cardiac toxicity in the anaesthetized guinea-pigs and effect of heparin infusion.

We have examined the effects of heparin infusion on the arrhythmias induced by digoxin. Digoxin treatment consisted of 0.6 mg kg-1 given i.v. 15 min after the beginning of heparin infusion. Heparin infusions (1.7 IU, 3.4 IU and 6.8 IU kg-1 min-1) were begun 15 min before digoxin injection and continued for another 30 min. ECG, blood pressure, heart rate and arrhythmias were recorded starting 15 min before and continuing for 60 min after the digoxin injection. Heparin at the infusion rates of 3.4 IU and 6.8 IU kg-1.min-1 reduced significantly the arrhythmia scores. On the other hand, heparin did not significantly alter the arterial blood pressure and heart rate values affected by digoxin.

Animals↗
PubMed1980

Non-competitive inhibition of bradykinin, acetylcholine and histamine on guinea-pig ileum with streptomycin and vitamin K3.

Streptomycin and vitamin K3 were studied on the guinea-pig ileum for their effects on the cumulative dose-response curves of bradykinin, acetylcholine and histamine. Streptomycin and vitamin K3 antagonized each of these agonists non-competitively. The comparison of the non-competitive affinities of the antagonists indicate that all of these agonists antagonized by a common mechanism.

Acetylcholine↗