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E Barabas

Publications and source records attributed to E Barabas.

At least 19 recordsLinked to original sources
PubMed1996

Active site-directed thrombin inhibitors: alpha-hydroxyacyl-prolyl-arginals, new orally active stable analogues of D-Phe-Pro-Arg-H.

D-alpha-Hydroxyacyl-prolyl-arginals, a new type of analogues of D-Phe-Pro-Arg-H (R1), have been prepared and evaluated. Unlike R1, whose terminal group is NH2, the new analogues with a terminal OH group are stable, as are the N-substituted derivatives of R1, that is, D-MePhe-Pro-Arg-H (R2), the highly potent and selective thrombin inhibitor, and Boc-D-Phe-Pro-Arg-H (R3), the much less favorable analogue. The most notable of the new analogues corresponds to the general formula D-Xaa-Pro-Arg-H, wherein Xaa means the acyl residue of mandelic acid (Man, 1), diphenyllactic acid (Dpl, 2), hexahydrophenyllactic acid (Hpl, 3), or hexahydromandelic acid (Hma, 4). In plasma clotting assays, 1 to 4 appeared to inhibit thrombin as well as some other clotting enzymes involved in thrombin generation, whereas R1 and R2 seemed to produce anticoagulation through inhibition of thrombin only. In the fibrin plate assay, 1 to 4 possessed even more moderate antifibrinolytic activities than R2. In in vivo evaluation in rats and rabbits, 2 to 4 proved to be potent anticoagulants/antithrombotics even on oral administration in a dose of 5 mg/kg. In view of these findings with the alpha-hydroxyacyl-prolyl-arginals, it is very likely that the less favorable biologic properties of Boc-D-Phe-Pro-Arg-H are due to the hydrophobicity and bulkiness of the terminal Boc-NH rather than its neutrality.

Administration, Oral↗
PubMed1993

Screening for fibrinolysis inhibitory effect of synthetic thrombin inhibitors.

Fibrin plate assay (FPA) and thrombelastography (TEG) were used to assess the antifibrinolytic effects of D-Phe-Pro-Arg-H (1), the prototype of peptide aldehyde inhibitors of thrombin, and two of its more stable derivatives, D-MePhe-Pro-Arg-H (2) and Boc-D-Phe-Pro-Arg-H (3). Inhibition of plasmin generation by tissue plasminogen activator, urokinase and streptokinase were studied by both FPA and TEG while that of plasmin could only be examined by FPA. TEG was more sensitive than FPA in general and for the detection of streptokinase inhibition in particular. Derivative (3) was 2-50 times more inhibitory than (1) or (2) depending on the enzyme studied and the assay system used. The thrombin selectivities of (1)-(3) were defined as the thrombin to fibrinolytic enzyme potency ratios. Data obtained by the FPA and thrombin time assay indicated (1) and (2) to be 2-80 times more selective for thrombin than (3). On the other hand, the values determined by TEG and recalcification assay showed the thrombin selectivity of (2) to be two to three times higher than that of (1), and (3) to have no such selectivity. According to TEG studies, (1) and (2) assisted rather than inhibited fibrinolysis by reducing the elasticity of human plasma clots.

Evaluation Studies as Topic↗
PubMed1990

Highly active and selective anticoagulants: D-Phe-Pro-Arg-H, a free tripeptide aldehyde prone to spontaneous inactivation, and its stable N-methyl derivative, D-MePhe-Pro-Arg-H.

D-Phe-Pro-Arg-H sulfate (GYKI-14166) is a highly active and selective inhibitor of thrombin both in vitro and in vivo. Recent studies on the stability of D-Phe-Pro-Arg-H in neutral aqueous solution at higher temperature have revealed that it is transformed into inactive 5,6,8,9,10,10a-hexahydro-2-(3'- guanidinopropyl)-5-benzyl-6-oxo- imidazo[1,2-a]pyrrolo[2,1-c]pyrazine. No such inactivation could be observed with Boc-D-Phe-Pro-Arg-H (GYKI-14451), but this compound was far less specific than the free peptide as it inhibited thrombin and, for instance, plasmin equally well. Assuming that the transformation of free tripeptide aldehyde, mentioned above, can only be initiated by a primary amino terminus, the N-alkyl derivatives of D-Phe-Pro-Arg-H were prepared. Of the new analogues, D-MePhe-Pro-Arg-H (GYKI-14766) proved to be as highly active and selective anticoagulant as its parent compound and was not inactivated by transformation into a heterocyclic compound.

Animals↗
PubMed1990

Protection from stress of tracheal intubation with midazolam-sufentanil neuroleptanalgesia.

Although diazepam has been shown to reduce the stress response, the protective effect of midazolam, a newer benzodiazepine from a stressful event, tracheal intubation, has not been studied as yet by catecholamine assays in patients undergoing coronary artery bypass surgery, who also receive intravenous sufentanil as a component of the neuroleptanalgesic technique. Therefore, we evaluated the influence of midazolam in combination with sufentanil on the plasma free catecholamines before and after midazolam, after sufentanil and pancuronium and before and after intubation in 15 adult patients undergoing coronary artery surgery. After routine premedication, midazolam 0.14 +/- 0.01 mg.kg-1 i.v. was given over 1 min followed 5 min later by sufentanil in incremental i.v. doses of 1.5 micrograms.kg-1 to a total pre-intubation dose of 4.0-5.0 micrograms.kg-1 injected in 10 min. The incremental doses of sufentanil were given when a greater than 15 per cent increase in rate-pressure product occurred. One min after the initial dose of sufentanil, pancuronium 0.1 mg.kg-1 i.v. was given to provide muscle relaxation. Midazolam administration per se caused a significant decrease in systolic and diastolic blood pressures with a concomitant reduction in systemic vascular resistance. Sufentanil reduced the left ventricular stroke-work index. Tracheal intubation, a strong stressor during anesthesia, elicited no increase in catecholamines and/or adverse hemodynamic responses in contrast to a marked increase in plasma catecholamines routinely observed in patients anesthetized by the commonly used technique of intravenous barbiturates in combination with succinylcholine.

Aged↗
PubMed1988

Esmolol attenuates tachycardia caused by tracheal intubation: a double-blind study.

A new cardioselective and rapidly metabolized beta-blocker, esmolol (E), was given to prevent post-intubation tachycardia in 40 ASA Class PS I-II patients induced with thiopental, succinylcholine, N2O: O2 and enflurane sequence. The control group (A, n = 10) received 5% D/W. Three study groups received E loading doses of 500 micrograms/kg/min for 1 min (B, n = 8), 2 min (C, n = 10) and 4 min (D, n = 12); the continuous i.v. maintenance doses were 100, 200 and 300 micrograms/kg/min for a total of 10 min, respectively. The pre-esmolol heart rates were 85 +/- 4 in group A, 80 +/- 5 in B, 77 +/- 5 in C, 83 +/- 5 in D; at anesthetic induction and at 4 min after E-infusion, heart rates were 93 +/- 5, 65 +/- 4, 71 +/- 4, 70 +/- 5, respectively; three min post-intubation heart rates were in the control group 111 +/- 4 and 82 +/- 5, 93 +/- 5, 85 +/- 4, respectively, in the E-treated groups. Group A showed marked tachycardia (p less than or equal to 0.001) not observed in the treated groups B, C, D. A significant blockade of HR increases at all infusion rates of E (p less than or equal to 0.05) was found. E at all doses reduced the significant increase in BP observed in Group A. Catecholamine increases were identical and not significantly different among the groups. No adverse effects e.g. bradycardia, arrhythmias and hypotension caused by E or intubation were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

Endocrine and hemodynamic effects of antagonism of fentanyl-induced respiratory depression by nalbuphine.

Endocrine and hemodynamic changes associated with the antagonism of fentanyl by nalbuphine have not been reported. Therefore, the authors studied ten patients after anesthetic induction with thiopental, fentanyl, tracheal intubation aided by succinylcholine and maintenance with diazepam, pancuronium, N2O, and further doses of fentanyl. Eight of the patients underwent cholecystectomy, one had a hysterectomy, and another had an abdominoplasty. After reversal of neuromuscular block at the conclusion of surgery, normal ventilation was restored by 0.22 +/- 0.02 mg/kg intravenous nalbuphine (mean +/- SEM). Plasma levels of free norepinephrine, histamine, and cortisol did not increase after antagonism of the fentanyl-induced respiratory depression, but plasma concentration of epinephrine increased significantly but without significant hemodynamic changes. Minute ventilation was 1.5 +/- 0.4 L/min before and 11 +/- 1, 10 +/- 1, 11 +/- 1, and 10 +/- 1 L/min at 15, 30, 45, and 60 min after antagonism; corresponding PaCO2 levels were 56 +/- 2, 44 +/- 1, 49 +/- 7, 49 +/- 1, 42 +/- 1 mm Hg. The mean analogue pain score remained below 1.5. We conclude that nalbuphine effectively antagonizes fentanyl-induced respiratory depression without adverse endocrine and circulatory changes or loss of analgesia.

Adult↗
PubMed1987

Diazepam causes no adverse cardiocirculatory effects in cardiac patients.

The effects of diazepam on hemodynamic measures and catecholamine levels were studied in 25 patients before administration of any other anesthetic or analgesic agent, for coronary artery bypass graft surgery. The patients were spontaneously breathing 40% oxygen in air, and no postural changes or surgical manipulations were allowed before or during the study. Before and ten minutes after completion of the intravenous infusion of 0.4 mg/kg of diazepam over five minutes, the following hemodynamic variables were determined: direct radial artery pressure, pulmonary artery pressure, central venous pressure, cardiac output by thermodilution in triplicate via a balloon-tipped pulmonary artery catheter and electrocardiograms. Norepinephrine, epinephrine, and dopamine levels were determined by liquid chromatography. Significant (P less than 0.05) reductions in pulmonary artery systolic pressure, systolic systemic blood pressure, and epinephrine levels were observed after diazepam administration. No other hemodynamic changes were statistically significant. Thus diazepam alone caused no adverse hemodynamic or endocrine effects in cardiac surgical patients. It is concluded that the use of diazepam is not contraindicated in cardiac patients with reduced myocardial oxygen supply as a consequence of coronary sclerosis.

Catecholamines↗
PubMed1987

Nalbuphine as an analgesic component in balanced anesthesia for cardiac surgery.

The efficacy and safety of nalbuphine hydrochloride as an IV analgesic used in combination with pretreatment and supplemental doses of diazepam with and without N2O were assessed in 15 patients scheduled to undergo aortocoronary bypass (n = 11) or valve replacement surgery (n = 4). The loading infusion of 3.0 mg/kg nalbuphine given in 20 min 5 min after conclusion of IV injection of 0.4 mg/kg/5 min diazepam caused no significant changes in systolic or diastolic systemic and pulmonary arterial blood pressures or in heart rate, cardiac index, stroke index, systemic and pulmonary vascular resistance, or right and left ventricular stroke work index. After the initial 1-hr loading infusion of 6.66 +/- 0.89 mg/kg nalbuphine (mean +/- SE), additional nalbuphine infusion maintenance doses of 4.73 +/- 0.77, 1.87 +/- 0.31, 2.16 +/- 0.23, 1.65 +/- 0.22, and 2.35 +/- 0.44 were used in the subsequent hourly periods to maintain a pain-free state throughout surgery. Hemodynamic changes during the three most stressful periods, tracheal intubation, skin incision, and sternotomy, were not statistically significant. Normal plasma catecholamine and cortisol levels indicate that these patients experienced neither stress nor pain during the maintenance of anesthesia. Nalbuphine caused no significant histamine release. All patients had uncomplicated maintenance of and emergence from anesthesia.

Adult↗
PubMed1987

Midazolam causes no adverse hemodynamic effects in cardiac patients.

The effects of midazolam on hemodynamic measures were evaluated in 30 patients scheduled for cardiac surgery. The patients were spontaneously breathing 40% oxygen in air and no postural changes or surgical manipulations were allowed before or during the study. Before and 10 minutes after completion of the intravenous infusion of 0.2 mg/kg of midazolam, the following hemodynamic variables were determined: direct radial artery pressure, pulmonary artery pressure, central venous pressure, cardiac output by thermodilution in triplicate via a Swan-Ganz pulmonary artery catheter, and electrocardiograms. Significant (P less than 0.05) reductions in systolic systemic blood pressure, systemic vascular resistance, systemic diastolic blood pressure, and left ventricular stroke work index were observed after midazolam administration. No other hemodynamic changes were statistically significant. Thus midazolam per se caused no adverse, but rather favorable, cardiocirculatory effects since it reduced cardiac work without altering cardiac contractility.

Blood Pressure↗
PubMed1986

The inhibitory effect of esmolol on human plasmacholinesterase.

Esmolol, a new cardioselective beta adrenergic blocker inhibits plasmacholinesterase activity in vitro. The concentration of esmolol hydrochloride that inhibits by 50 per cent the hydrolysis of 50.0 mumol.L-1 benzoylcholine hydrochloride by 1:200 diluted, heparinized pooled plasma of six healthy volunteers at 37 degrees C and 240 nm, determined by the ultraviolet spectrophotometric method of Kalow, was 50 mumol.L-1. Esmolol's primary metabolite, 3-[4-(2-hydroxy-3-(isopropylamino)propoxy)-phenyl]propionic acid, had an I50 = 190 mumol.L-1. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 micrograms.kg-1.min-1 for 4 minutes were 58.6 +/- 6.2 mumol.hr-1.ml-1 (mean +/- SE) before and 55.1 +/- 6.6 mumol.hr-1.ml-1 after the infusion. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 micrograms.kg-1.min-1 for two minutes and 200 micrograms.kg-1.min-1 for an additional two minutes were 70.2 +/- 8.9 mumol.hr-1.ml-1 before and 69.1 +/- 9.5 mumol.hr-1.ml-1 after the infusion. The pre- and post-infusion plasmacholinesterase activities were not significantly different. Since plasmacholinesterase is responsible for the hydrolysis of succinylcholine and that of the ester-type local anaesthetics this lack of in vivo interaction of esmolol with the hydrolysis of these drugs should be further confirmed by experiments with these combinations in man.

Anesthesia↗
PubMed1985

The inhibitory effect of glycopyrrolate on human plasma-cholinesterase.

The in vitro inhibitory effect of glycopyrrolate and atropine on the hydrolysis of benzoylcholine at 50.0 microM concentration was determined in the plasma of 6 healthy volunteers at 37 degrees C and at 240 nm by the ultraviolet spectrophotometric method of Kalow. The 50 per cent inhibitory concentration (I50) of glycopyrrolate was found to be 1.0 mM and the I50 of atropine was 0.9 mM. This inhibitory effect of glycopyrrolate and atropine is moderate but its interaction with the in vivo hydrolysis of succinylcholine or that of ester-type of local anaesthetics in patients should be further studied. Although both glycopyrrolate and atropine inhibit PChE to the same extent, glycopyrrolate should be utilized in patients in whom inhibition of brain PChE or central effects ought to be avoided, since glycopyrrolate does not penetrate the blood-brain barrier.

Atropine↗
PubMed1976

Hirudin.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMedDate not supplied

The effect of some enkephalins on calcitonin secretion.

Synthetic enkephalins: 5 metenkephalin, D2 proenkephalin and 5 leuenkephalin and morphine were injected into cerebral ventricles of rats. After 30 minutes the rats were sacrificed and the calcitonin content of the thyroid was assayed. As compared to the controls, morphine reduced significantly the secretion of calcitonin. Of the enkephalins, only 5 leuenkephalin had a borderline effect on calcitonin secretion, stimulating to a significant degree the rise of the hormone. The data obtained demonstrate the selective effect of opiates on calcitonin secretion.

Animals↗
PubMedDate not supplied

Effects of some m-cholinomimetics and alpha- and beta-adrenomimetics on cyclic-AMP content of the rat submaxillary gland.

The experiments were performed on four groups of rats of both sexes, anesthetized with pentobarbital: one control and three experimental groups. The experimental group was treated with carbachol 50 micrograms/100 g, isoprenaline 10 micrograms/100 g and phenylephrine 10 micrograms/100 g, respectively. The cyclic AMP was assayed by a R.I.A. method, at 4-6 min after administration of the drugs. The salivary secretion was estimated semiquantitatively by qualifying adjectives: very copious, copious and absent. In the control group the concentration of cAMP was 699 +/- 212 p.mol/g of wet tissue; carbachol administration resulted in an important and statistically significant increase (1030 +/- 205 p.mol/g; P less than 0.001) and isoprenaline increased the cAMP concentration more than twice (1414 +/- 368 p.mol/g, P less than 0.001). Phenylephrine decreased the level of cAMP to 481 +/- 79 p.mol/g, the decrease being statistically significant (0.02 less than p less than 0.05).

Animals↗
PubMedDate not supplied

Effect of magnesium ion upon the calcitonin content of rat thyroid.

Thyroid calcitonin level was assayed in male rats after administration of magnesium gluconolactate. The resulting acute hypermagnesemia caused a significant decrease in calcitonin. However, calcemia showed unimportant changes, which suggests that the inhibitory action of magnesium is exerted directly on calcitonin secretion and is not affected by the calcium ion.

Animals↗