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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 61 (1987), S. 58-62 
    ISSN: 1432-0738
    Keywords: Soman ; iso-OMPA ; Interaction ; Acetylcholinesterase ; Carboxylesterases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague-Dawley rats, injected with the irreversible acetylcholinesterase (AChE) inhibitor soman (pinacolyl methylphosphonofluoridate) 25 μg/kg sc, showed no signs of toxicity. Pretreatment with iso-OMPA (tetra-isopropylpyrophosphoramide) 1 mg/kg sc 1 h before the soman administration, caused severe signs of hypercholinergic activity, similar to those seen with an acute signs-producing nonlethal dosage (100 μg soman/kg sc). Within 1 h iso-OMPA alone significantly reduced the activity of carboxylesterases (CarbE) in all tissues studied and butyrylcholinesterase (BuChE) activity was significantly reduced in plasma (22%) and liver (27%). Soman (25 μg/kg) alone significantly reduced the plasma activity of CarbE (15%), BuChE (53%) and AChE (18%), but had no effect on these enzymes of liver. The combined treatment of iso-OMPA and soman, however, reduced CarbE activity in liver (0%) and produced significantly greater effects than iso-OMPA or soman alone on AChE and BuChE in all the brain areas and skeletal muscles tested. The number of necrotic lesions found in skeletal muscles was many times higher with the combined treatment than seen with soman (25 μg/kg) alone, and was equal to those seen with an acute toxicity signs-producing dose of soman. It is concluded that the observed iso-OMPA-induced potentiation of soman toxicity is probably caused via reduced nonspecific binding sites (BuChE and CarbE) for soman leading to greater inhibition of AChE.
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  • 2
    ISSN: 1432-1041
    Keywords: Nicorandil ; vasodilator ; continuous infusion ; blood pressure ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics and haemodynamic effects of nicorandil after a 12-h infusion. Nicorandil is a mixed vasodilator combining the actions of a nitrate and a potassium channel opener. Nicorandil was infused for 12 h in 21 healthy volunteers at rates of 0.05, 0.10, and 0.20 μg·kg−1·min−1 using a placebo controlled, crossover design. Systemic blood pressure, heart rate, electrocardiographic (ECG) intervals, and cardiac output (impedance cardiography) were measured supine and standing. Dose-related, steady-state plasma nicorandil concentrations occurred within 3 to 4 h. Nicorandil's pharmacokinetics were linear with dose. Four 0.20 μg·kg−1·min−1 nicorandil infusions were terminated early primarily because of moderate or severe headaches. There were no safety concerns (ECG intervals, laboratory assays). Blood pressure fell versus placebo only in the standing position and heart rate increased slightly (not significant). That is, standing blood pressure in the 6 to 12 h interval fell from baseline 8.0*/6.8, 1.6/5.1, and 9.8*/7.9* mmHg (systolic/diastolic, *=P〈0.05 versus placebo) at 0.05, 0.10, and 0.20 μg·kg−1·min−1 respectively. Cardiac output increased slightly above placebo at lower doses. Haemodynamic changes correlated poorly with plasma nicorandil concentrations. Similar total doses were less well-tolerated when extended over 12 h. We saw no evidence of pharmacodynamic tolerance to nicorandil within 12 h.
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  • 3
    ISSN: 1432-1076
    Keywords: Indomethacin ; Drug level monitoring ; Very low birth weight infants ; Ductus arteriosus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI2 and PGE2, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.
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  • 4
    ISSN: 1432-1076
    Keywords: Fetal ; Urology ; Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The suspected diagnosis of urological disorders made on the basis of antenatal ultrasonography was compared with the final outcome in 23 cases. In 18 cases the initial diagnosis could be confirmed, whereas 5 showed no postnatal urological anomalies. Further efforts should be undertaken to improve prenatal diagnosis in order to facilitate treatment as early as possible.
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  • 5
    ISSN: 1432-1076
    Keywords: SVT ; ATP ; Infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine triphosphate (ATP- a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of Striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficacy and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficacy of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects.
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  • 6
    ISSN: 1432-1041
    Keywords: Nicorandil ; vasodilator ; tolerance study ; blood pressure ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of intravenous nicorandil, a mixed arterial and venous vasodilator, in 48 healthy volunteers. Nicorandil (20, 28, 39, 54, 74, 103, 144, or 200 μg·kg−1) or placebo were given over 5 min to subjects supine (16 subjects, 2 doses) or sitting (32 subjects, 1 dose) in a single-blind crossover design. Electro-cardiographic intervals, blood pressure, and heart rate were measured before and for 8 h after dosing. Blood and urine safety laboratory studies were also performed before and after dosing. All intravenous infusions of nicorandil and placebo were well tolerated and there were no clinically important safety concerns. The most frequent adverse event after nicorandil was headache (24 events by 19 subjects), although its occurrence was not strictly dose related. One subject experienced transient symptomatic hypotension (144 μg·kg−1). Mean plasma nicorandil concentrations were dose-related and fell with a half-life of 0.7 to 1.2 h. Systemic clearance and volume of distribution tended to decrease as dose increased. Sitting subjects showed marginally lower (〈20%) systemic clearances and larger values of Cmax and AUC. Nicorandil produced dose-related reductions in blood pressure, with consistent statistically significant differences from placebo after the 144 and 200 μg·kg−1 doses. The falls in blood pressure were greater for diastolic pressure and in this supine position. At 200 μg·kg−1, the mean falls in systolic/diastolic pressures (mm Hg) during the first hour were 10.9/14.7 supine and 6.1/9.1 sitting; systolic pressure returned to baseline after 8 h and diastolic pressure after 4 h. Heart rate increased transiently (mean peak increase of 17–24 bpm at the end of the 144 and 200 μg·kg−1 infusions). Blood pressure and heart rate changes over time were statistically significantly correlated with plasma nicorandil concentrations. Individual areas under the blood pressure and heart rate change curves likewise correlated with plasma concentration curve areas.
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  • 7
    ISSN: 1432-1076
    Keywords: Key words     Adenosine ; Supraventricular tachycardia ; Infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract      Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine-tri-phosphate (ATP) (a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficiency and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficiency of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects. Conclusion     There could be a role for adenosine or ATP for safe termination of most cases of SVT in infancy before transferring these infants to a specialised paediatric cardiology department.
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  • 8
    ISSN: 1432-1076
    Keywords: Key words     SVT ; ATP ; Infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract      Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine triphosphate (ATP- a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of Striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficacy and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficacy of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects. Conclusion     Adenosine or ATP could be the drug of choice for the treatment of junctional tachycardia in infants after vagal manoeuvres have failed. Provided continuous ECG monitoring is performed during injection, adenosine or ATP may be diagnostic in other types of supraventricular tachycardia and even in wide-complex tachycardia. We suggest a bolus injection of 0.5–1.0 mg/kg to be used prior to transport to the paediatric cardiology unit.
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  • 9
    ISSN: 1432-1076
    Keywords: Adenosine ; supraventricular tachycardia ; Infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine-tri-phosphate (ATP) (a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficiency and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficiency of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects. There could be a role for adenosine or ATP for safe termination of most cases of SVT in infancy before transferring these infants to a specialised paediatric cardiology department.
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  • 10
    ISSN: 1432-2242
    Keywords: Key words Gene flow ; Hybridization ; Sunflowers ; Transgenes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The development of transgenic plants has heightened concern about the possible escape of genetically engineered material into the wild. Hybridization between crops and their wild relatives provides a mechanism by which this could occur. While hybridization has been documented between several crops and wild or weedy relatives, little is known about the persistence of cultivar genes in wild populations in the generations following hybridization. Wild and weedy sunflowers occur sympatrically with cultivated sunflowers throughout much of the cultivation range, and hybridization is known to occur. We surveyed two cultivar-specific RAPD markers in 2700 progeny in a naturally occurring population of wild Helianthus annuus over five generations following a single generation of hybridization with the cultivar. Moderate levels of gene flow were detected in the first generation (42% hybrids at the crop margin) and cultivar allele frequencies did not significantly decline over four subsequent generations. These results indicate that gene flow from cultivated into wild populations of sunflowers can result in the long-term establishment of cultivar alleles in wild populations. Furthermore, we conclude that neutral or favorable transgenes have the potential to escape and persist in wild sunflower populations.
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