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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of insect behavior 1 (1988), S. 111-115 
    ISSN: 1572-8889
    Keywords: Coleoptera ; Anobiidae ; Anobium punctatum ; sex pheromone ; flying beetles ; wind tunnel ; Stegobium paniceum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 2
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    Cellular and molecular life sciences 44 (1988), S. 101-104 
    ISSN: 1420-9071
    Keywords: Platelets ; calcium ; phospholipase A2 ; G-proteins ; arachidonic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A major route for the release of arachidonic acid from platelet phospholipids appears to be catalyzed by a phospholipase A2 that can be stimulated by a rise of cytosolic Ca2+. This paper discusses certain other mechanisms for regulation of this process. Release of arachidonic acid by calcium ionophores is potentiated by pretreatment with stimulators of protein kinase C; e.g. diglyceride, phorbol esters and the terpene diester mezerein. This effect appears to be coincident with phosphorylation of a certain group of proteins (not 47 KDa protein), and is sensitive to depletion of ATP, activation of Ca2+ dependent phosphatase, and the kinase C inhibitor H-7, but is unaffected by Na+/H+ exchange inhibitors. Recent results in other cell types strongly indicate that phospholipase A2 is also directly under control of certain GTP-binding proteins.
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  • 3
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    Cellular and molecular life sciences 44 (1988), S. 657-666 
    ISSN: 1420-9071
    Keywords: Ionic currents ; vibrating probe ; membrane potential ; fucoid egg polarization ; animal-vegetal polarity ; polarization ; voltage gradients ; calcium ; vesicle secretion ; Achlya ; oocytes ; insect follicle ; insect ovariole ; polarized transport ; egg activation ; mouse blastomere ; epithelial morphogenesis ; limb bud
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Morphogenetic fields must be generated by mechanisms based on known physical forces which include gravitational forces, mechanical forces, electrical forces, or some combination of these. While it is unrealistic to expect a single force, such as a voltage gradient, to be the sole cause of a morphogenetic event, spatial and temporal information about the electrical fields and ion concentration gradients in and around a cell or embryo undergoing morphogenesis can take us one step further toward understanding the entire morphogenetic mechanism. This is especially true because one of the handful of identified morphogens is Ca2+, an ion that will not only generate a current as it moves, but which is known to directly influence the plasma membrane's permeability to other ions, leading to other transcellular currents. It would be expected that movements of this morphogen across the plasma membrane might generate ionic currents and gradients of both electrical potential and intracellular concentration. Such ionic currents have been found to be integral components of the morphogenetic mechanism in some cases and only secondary components in other cases. My goal in this review is to discuss examples of both of these levels of involvement that have resulted from investigations conducted during the past several years, and to point to areas that are ripe for future investigation. This will include the history and theory of ionic current measurements, and a discussion of examples in both plant and animal systems in which ionic currents and intracellular concentration gradients are integral components of morphogenesis as well as cases in which they play only a secondary role. By far the strongest cases for a direct role of ionic currents in morphogenesis is the polarizing fucoid egg where the current is carried in part by Ca2+ and generates an intracellular concentration gradient of this ion that orients the outgrowth, and the insect follicle in which an intracellular voltage gradient is responsible for the polarized transport from nurse cell to oocyte. However, in most of the systems studied, the experiments to determine if the observed ionic currents are directly involved in the morphogenetic mechanism are yet to be done. Our experience with the fucoid egg and the fungal hypha ofAchlya suggest that it is the change in the intracellular ion concentration resulting from the ionic current that is critical for morphogenesis.
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  • 4
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    Entomologia experimentalis et applicata 47 (1988), S. 173-182 
    ISSN: 1570-7458
    Keywords: Bembidion lampros ; Pterostichus cupreus ; Carabidae ; Coleoptera ; behaviour ; temperature ; searching ; consumption ; cereal aphid ; Rhopalosiphum padi ; prey ; density ; barley
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé Les taux maximum de consommation de R. padi L. à différentes températures ont été déterminés au laboratoire chez deux carabes, B. lampros Herbstet P. cupreus L. La consommation moyenne a augmenté avec la température chez les deux espèces, B. lampros consommant un maximum de 15,9 larves des stades 1 à 3 et 9,1 pucerons adultes aptères, à 25°C. P. cupreus a été particulièrement vorace et a consommé 125,3 adultes aptères par jour à 20°C. Le comportement des deux espèces a été observé en filmant en vidéo des carabes à jeun, maintenus à différentes températures constantes, dans des enceintes semées en orge de printemps. Des éléments du comportement, communs aux deux espèces, ont été définis: 1) immabilité, 2) marche et course, 3) recherche, 4) affrontement. P. cupreus a été plus actif à toutes les températures, B. lamprosa été inactif au-dessous de 10°C. La part de temps consacrée à la recherche, le nombre de plantes prospectées, et la vitesse ont augmenté avec la température chez les deux espèces. Dans des enceintes similaires colonisées par R. padi, P. cupreus a significativement augmenté le temps consacré à la recherche dans les enceintes, parallèlement à l'augmentation de la densité des pucerons. Après la découverte d'une colonie de pucerons, P. cupreus escalade et prospecte la plante et ses voisines immédiates; tandis que les plantes des enceintes sans pucerons sont rarement escaladées. B. lampros n'a pas été observé escaladant des plantes d'enceintes avec ou sans pucerons, et il n'a pas accru son temps de prospection en fonction de la densité de pucerons. Les quelques B. lampros qui ont capturé des pucerons l'ont fait lorsque ceux-ci marchaient sur la surface du sol. La discussion a porté sur l'efficacité relative des deux carabes comme prédateurs de R. padi, et les résultats ont été comparés à ceux d'études du même type, menées ailleurs, avec des prédateurs de Sitobion avenae sur blé d'hiver.
    Notes: Abstract Maximum consumption rates were determined for two carabids, Bembidion lampros Herbst. and Pterostichus cupreus L., feeding on the cereal aphid Rhopalosiphum padi L. at different temperatures in the laboratory. Mean daily consumption increased with increasing temperature for both species, B. lampros consuming a maximum of 16 1–3 instar nymphs and 9 apterous adult aphids at 25°C. P. cupreus was particularly voracious and consumed 125 apterous adult R. padi per day at 20°C. The behaviour of both species was analysed by video filming starved beetles, maintained at different constant temperatures, in arenas sown with spring barley. The behavioural components (1) still; (2) run/walk; (3) search and (4) confrontation were identified and were common to both species. P. cupreus was more active over the temperature range tested; B. lampros was inactive under 10°C. The proportion of time spent searching, number of plants searched, and velocity increased with increasing temperature for both species. When observed in similar arenas seeded with R. padi colonies, individuals of P. cupreus significantly increased their time spent searching in arenas with increasing aphid density. Following discovery of an aphid colony, individuals climbed and searched the host plant and its nearest neighbours. Plants in aphid free arenas were rarely climbed. B. lampros was not observed climbing in either aphid free arenas or in arenas with increasing aphid densities, and did not significantly increase its time spent searching in response to increased prey density. The few B. lampros that found aphids caught them walking on the soil surface. The relative efficiences of these two carabids as predators of R. padi are discussed, and the results are compared with similar studies elsewhere with predators of Sitobion avenae on winter wheat.
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  • 5
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    Entomologia experimentalis et applicata 48 (1988), S. 43-50 
    ISSN: 1570-7458
    Keywords: Coleoptera ; Carabidae ; Pterostichus ; mandible size ; wear pattern ; feeding behaviour ; burrowing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'analyse de l'influence de la texture des aliments et du fouissage, sur l'usure des mandibules a été effectuée en nourrissant P. melanarius avec des aliments de différentes duretés dans des récipients contenant ou non du sol. Les aliments durs seuls usent moins le bord incisif (extrémité de la mandibule) et la surface coupante, que leur association avec le fouissage. En présence exclusive d'aliments durs, les femelles avaient érodé plus vite leurs mandibules que les mâles, tandis que chez ceux-ci le fouissage seul les avaient usé plus vite que chez les femelles. Des femelles récoltées dans un champ de céréales contenaient plus d'aliments durs que les mâles. Les différences de comportement avaient provoqué apparemment des types d'usure différents suivant les sexes. Les adultes usent leurs mandibules au cours de leur première année de vie imaginale. Cependant, la taille des mandibules des femelles échantillonnées dans la nature correspondait mieux à celle des femelles (de même âge) provenant des expériences ayant provoqué une forte usure (aliment dur et fouissage du sol). Les mandibules des mâles échantillonnés présentaient seulement une usure modérée et ressemblaient à celles des mâles ayant consommé soit des aliments durs, soit foui le sol. La discussion a traité des relations entre l'usure des mandibules, la fécondité et la longévité de P. melanarius et d'autres espèces de carabes.
    Notes: Abstract The effects of food texture and burrowing on mandible wear in the predatory carabid beetle Pterostichus melanarius Illiger were investigated by feeding adults soft or hard food in jars with or without soil. Both the incisor cusp (mandible tip) and cutting surface of the mandibles erode more in response to the combination of hard food and burrowing than to hard food alone. Females were found to erode their mandibles more than males in the hard-food-only treatment, whereas males wore down their mandibles more than females in the soil-only treatment. Female P. melanarius collected in a cereal field contained signficantly more solid food items compared with males. Differences in behaviour apparently resulted in differential wear patterns between the sexes. It is shown that the process of mandible wear in P. melanarius will result in worn mandibles in their first year as adults. However, mandible size of field-sampled females were found to be best correlated with females (of similar age) in the experiment exhibiting extensive wear (foraged hard food and burrowed in soil). The mandibles of field-sampled males were similar to those of males in the hard-food-only and the soil-only treatments, which showed only slight to moderate wear. The influence of mandible wear on fecundity and survival in P. melanarius as well as in other carabid species is discussed.
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  • 6
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    Entomologia experimentalis et applicata 46 (1988), S. 47-54 
    ISSN: 1570-7458
    Keywords: Coleoptera ; Curculionidae ; Sitophilus ; S. oryzae ; S. zeamais ; rice weevil ; maize weevil ; geographical strains ; digestion ; amylase ; diet ; barley ; corn ; maize ; rice ; wheat ; amylase inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé La transformation de rang des valeur d'activité spécifique de l'α-amylase de 4 souches de S. oryzae et de 4 souches de S. zeamais montre que les niveaux les plus élevés de ces enzymes prédominantes s'observent chez les adultes nourris d'orge mondé ou de riz brun á grains longs. Des niveaux intermédiaires d'activité ont été obtenus chez les insectes élevés sur maïs jaune, et les niveaux les plus faibles chez ceux élevés sur blé. Bien que les extraits préparés à partir d'orge présentent une activité inhibitrice de deux isoamylases purifiées de S. oryzae, les niveaux des inhibiteurs naturels α-amylase de ces deux enzymes sont environ respectivement 2,2 et 6,1 fois plus concentrés dans le blé. L'ingestion de ces inhibiteurs d'amylase et la formation d'un complexe enzyme inactive/inhibiteur avec l'amylase secrétée antérieurement, peut rendre compte de la plus faible activité de l'amylase chez les charançons consommant du blé. Le niveau d'amylase de S. oryzae est 2 fois plus élevé que celui de S. zeamais pour toutes les souches élevées sur un régime donné. Des niveaux d'activité significativement différents ont été trouvés suivant les souches pour chacune des deux espèces. Puisque l'amylase est la principale hydrolase digestive de ces espèces, l'intensité de la modification des teneurs en amylase par la consommation de céréales peut indiquer leur adéquation comme hôtes potentiels.
    Notes: Abstract Rank transformation of specific activity values of α-amylase across four strains of Sitophilus oryzae (L.) and four strains of S. zeamais Motschulsky indicates that levels of these predominant enzymes are highest in adults feeding on hulled barley or long-grain brown rice. Intermediate activity levels are found in weevils feeding on yellow corn (maize) and lowest levels are found in wheat-fed weevils. Although extracts prepared from barley contain inhibitory activity against two purified isoamylases from S. oryzae, levels of the naturally-occurring α-amylase inhibitors against these two enzymes are about 2.2-fold and 6.1-fold, respectively, more concentrated in wheat. Ingestion of these amylase inhibitors and formation of an inactive enzyme:inhibitor complex with previously secreted amylase may account for the lower activity of amylase in weevils of both species feeding on wheat. Amylase levels across all strains feeding on a given diet are about 2-fold higher in S. oryzae than in S. zeamais. Significant differences in activity levels were also found between strains in both species. Since α-amylase is a predominant digestive hydrolase in these species, the degree to which cereal diets affect amylase levels may indicate their suitability as potential hosts.
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  • 7
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    Entomologia experimentalis et applicata 48 (1988), S. 157-163 
    ISSN: 1570-7458
    Keywords: sweet potato weevil ; Cylas formicarius elegantulus ; Coleoptera ; Curculionidae ; sweet potato ; Ipomoea batatas ; feeding ; host-plant preference ; leaf surface chemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Résumé L'étude a porté sur la consommation pendant 12 h, en boîtes de Pétri de diamètre 9 cm, de rondelles de 2 cm de diamètre de feuilles de 4 cultivars,—Centennial, Jewel, Resisto, Regal—, d'I. batatas par C. formicarius elegantulus. Les charançons ont consommé le long des nervures, préférant la face inférieure à la face supérieure des feuilles. Un index de consommation a été calculé en fonction de la longueur de nervure ayant servi à la consommation, rapportée à la longueur totale des nervures de la surface exposée. Les niveaux de consommation des mâles et des femelles étaient semblables. En présence de choix binaires, le cultivar Centennial a été le plus consommé, et le cultivar Resisto, le moins, par les femelles. De telles préférences n'ont pas été observées en l'absence de choix. La composition chimique de la surface de la feuille a été analysée par chromatographie en phase gazeuse. 8 pics principaux identiques ont été observés chez les 4 cultivars, mais ils avaient différentes hauteurs.
    Notes: Abstract A bioassay was developed to quantify the feeding of adult sweet potato weevils, Cylas formicarius elegantulus (Summers) (Coleoptera; Curculionidae) on the foliage of four cultivars (Centennial, Jewel, Resisto and Regal) of sweet potato (Ipomoea batatas (L.) Lam.) (Convolvulaceae). Weevils fed along the leaf veins, preferring the lower to the upper leaf surface. Males and females had similar levels of feeding. Different levels of feeding by female weevils were observed between cultivars in dual-choice bioassays with Centennial, a susceptible cultivar in field-plot experiments, being most preferred and Resisto least preferred. However, these feeding differences were not observed in no-choice bioassays. Little difference was observed in the leaf surface chemistry of the four cultivars.
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  • 8
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    Cellular and molecular life sciences 44 (1988), S. 936-944 
    ISSN: 1420-9071
    Keywords: Contractile system ; fetus ; premature myocardium ; calcium ; sarcoplasmic reticulum ; contractile protein ; sarcolemma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Recent studies regarding developmental changes in the myocardial contractile system from fetal, newborn, and adult animals are reviewed. From the data obtained so far, we conclude that in the early fetus myocardial contraction is mainly dependent on Ca which enters via the sarcolemma. Ca release from the sarcoplasmic reticulum is minimal. The role of the sarcoplasmic reticulum as a source of contractile Ca increases and the role of Ca influx across the sarcolemma in contractile system decreases with development.
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  • 9
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    European journal of clinical pharmacology 34 (1988), S. 77-82 
    ISSN: 1432-1041
    Keywords: N-acetylcysteine ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of N-acetylcysteine (NAC) have been determined after its intravenous and oral administration to 6 healthy volunteers. According to a randomized cross-over design each subject received NAC 200 mg i.v. and 400 mg p.o., and blood samples were collected for 30 h. Reduced NAC had a volume of distribution (VSS) of 0.59 l·kg−1 and a plasma clearance of 0.84 l·h−1·kg−1. The terminal half-life after intravenous administration was 1.95 h. The oral bioavailability was 4.0%. Based on total NAC concentration, its volume of distribution (VSS) was 0.47 l·kg−1 and its plasma clearance was 0.11 l·h−1·kg−1. The terminal half-life was 5.58 h after intravenous administration and 6.25 h after oral administration. Oral bioavailability of total NAC was 9.1%.
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  • 10
    ISSN: 1432-1041
    Keywords: BW443C ; enkephalin ; opioid peptide ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 µg·kg−1 for 60 min and increasing to a maximum of 2.0 µg·kg−1·min−1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 µg·kg−1·min−1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations 〉0.8 µg·ml−1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60–90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accomodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean ± SD plasma clearance of 123±18 ml·min−1 and a half-life of 2.0±0.4 h.
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  • 11
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    European journal of clinical pharmacology 34 (1988), S. 263-266 
    ISSN: 1432-1041
    Keywords: tyramine ; propranolol ; pressure response ; blood pressure ; beta-adrenoceptor blockers ; healthy volunteers ; indenolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect β-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1–6 mg, alternating with saline, in a randomized, single blind fashion. Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED15, i.e. the dose of tyramine required to increase systolic blood pressure by 15%.
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  • 12
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    European journal of clinical pharmacology 34 (1988), S. 315-317 
    ISSN: 1432-1041
    Keywords: albendazole ; echinococcosis ; bioavailability ; food intake ; fatty meal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the systemic availability of oral albendazole in 6 patients with echinococcosis either fasting or with breakfast. Albendazole sulphoxide, the pharmacologically active principle, was assayed by HPLC. Mean plasma concentrations and AUCs were 4.5 times higher when albendazole was given with breakfast than when administered in the fasting state. We conclude that therapy of echinococcosis with albendazole requires the drug to be taken with meals and that administration on an empty stomach might be more appropriate when intraluminal effects are desired, e.g. for intestinal parasites.
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  • 13
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    European journal of clinical pharmacology 34 (1988), S. 469-473 
    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min−1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.
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  • 14
    ISSN: 1432-1041
    Keywords: metoprolol ; controlled-release formulation ; pharmacokinetics ; pharmacodynamics ; exercise heart rate ; healthy volunteers ; efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and pharmacodynamic properties of a new multiple-unit, controlled-release (CR) formulation of metoprolol1 (metoprolol succinate, 95 mg once daily), which has almost constant (zero-order) release properties over most of a 24-h dose interval, have been compared with those of conventional metoprolol tablets (metoprolol tartrate, 100 mg once daily and 50 mg twice daily), in 12 healthy male volunteers. The steady-state plasma concentrations of metoprolol after five days of treatment varied less throughout the day with the CR than with the conventional formulation. This was associated with a considerably lower peak plasma concentration and the achievement of a significantly higher plasma concentration at the end of the dose interval. Similarly, the effect on exercise-induced tachycardia was maintained at a relatively constant level throughout the day after treatment with the CR formulation. A significantly greater effect 24 h after administration was achieved with the CR formulation, when compared with once-daily dosing with metoprolol tablets, 100 mg. Twice-daily dosing with metoprolol tablets, 50 mg, produced a similar β1-blocking effect at the end of the dose interval to that observed with metoprolol CR. Although the steady-state plasma concentrations indicated significantly lower systemic availability for the CR formulation, compared with both regimens of metoprolol tablets, the total effect over the dose interval, expressed as the area under the efficacy curve (AUEC), was similar for the three treatments. The relationship between steady-state plasma concentrations and the pharmacodynamic efficacy at corresponding times, indicated that plasma concentrations were more effectively utilized after the administration of the CR formulation than after the conventional tablet regimens. The results of this study clearly indicate the potential benefits offered by the new metoprolol CR formulation, under all circumstances where a constant degree of β1-selective blockade, without plasma peaks and troughs, is preferred.
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  • 15
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    European journal of clinical pharmacology 34 (1988), S. 211-212 
    ISSN: 1432-1041
    Keywords: diclofenac ; sulglicotide ; bioavailability ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p〈0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.
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  • 16
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    European journal of clinical pharmacology 34 (1988), S. 283-289 
    ISSN: 1432-1041
    Keywords: piroxicam ; tenoxicam ; cholestyramine ; accelerated drug elimination ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the influence of multiple oral doses of cholestyramine on the single dose pharmacokinetics of tenoxicam and piroxicam in eight healthy young volunteers. Each subject received on two occasions single intravenous injections of 20 mg tenoxicam and on another two occasions single oral doses of 20 mg piroxicam. Both medications were followed by multiple oral doses of either cholestyramine or plain water (placebo). Compared with placebo cholestyramine accelerated the elimination of both drugs. The average values of half-lives were reduced (tenoxicam: 31.9 h vs 67.4 h; piroxicam: 28.1 h vs 46.8 h) due to increases in clearance. Cholestyramine-mediated enhancement of drug elimination was most pronounced in the subjects with a comparatively low baseline drug clearance. Thus, intersubject variability in clearance was smaller when the drug administrations were followed by the anion-exchange resin. The twofold acceleration of tenoxicam elimination in the present study in man contrasts with a much larger effect (five-fold) seen in experiments with dogs. This points to a much easier access of unchanged tenoxicam to the intestinal lumen in the dogs than in man. Comparing the pharmacokinetics of tenoxicam and piroxicam in the same volunteers revealed a high degree of correlation in clearance and half-lives and similar intersubject variabilities in mean kinetic variables.
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  • 17
    ISSN: 1432-1041
    Keywords: rifampicin ; rifabutin ; microsomal enzyme induction ; healthy volunteers ; antimicrobial agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-β-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-β-hydroxycortisol, but the magnitude of the effects was signifiantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
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  • 18
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    European journal of clinical pharmacology 35 (1988), S. 21-24 
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 19
    ISSN: 1432-1041
    Keywords: metronidazole ; cimetidine ; pharmacokinetics ; drug interaction ; drug metabolism ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the effect of cimetidine on the pharmacokinetics of metronidazole was investigated in 6 healthy volunteers. Cimetidine 1.0 g/day was administered for 9-days and metronidazole 500 mg was administered orally on the second and eighth days, and in a control experiment. During cimetidine treatment the plasma kinetics of metronidazole and its partial clearance by renal excretion of the unchanged compound, glucuronidation, hydroxylation and oxidation to its acetic acid metabolite were not significantly different from the control values. The results indicate that cimetidine does not influence the pharmacokinetics or metabolism of a single oral dose of metronidazole.
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  • 20
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    European journal of clinical pharmacology 35 (1988), S. 69-75 
    ISSN: 1432-1041
    Keywords: L-carnitine ; pharmacokinetics ; intravenous and oral doses ; bioavailability ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 · h−1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.
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  • 21
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    European journal of clinical pharmacology 35 (1988), S. 89-91 
    ISSN: 1432-1041
    Keywords: flecainide acetate ; Wolff-Parkinson-White syndrome ; rectal absorption ; suppository ; micro enema ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The rectal absorption of flecainide from an aqueous solution, a fatty suppository and a polyethyleneglycol suppository was studied in one patient with supraventricular tachycardia (Wolff-Parkinson-White syndrome) refractory for oral anti-arrhythmic treatment. Rectal absorption was found to be fast (t1/2abs=1 h) and complete when flecainide was administered as a solution (relative bioavailability 100%). Flecainide was poorly absorbed from a fatty suppository. The polyethyleneglycol suppository gave absorption with a relative bioavailability of 80% and t1/2 abs=1.2 h.
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  • 22
    ISSN: 1432-1041
    Keywords: acetaminophen ; codeine ; clearance ; metabolite formation ; glucuronidation ; pharmacokinetics ; healthy volunteers ; drug interaction
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In nine healthy volunteers, the clearance and metabolism of acetaminophen 1000 mg i.v. was evaluated with and without two concomitant oral doses of codeine in order to investigate a possible interaction. Plasma acetaminophen was followed for 720 min and urine was collected for 24 h after each dose for determination of metabolites. When codeine was coadministered, the average total clearance of acetaminophen and its clearance by glucuronidation, sulphation and mercapturate formation were 0.58 to 1.12-times the control values. It is concluded that therapeutic doses of codeine do not influence the clearance or metabolism of acetaminophen.
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  • 23
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    European journal of clinical pharmacology 35 (1988), S. 183-185 
    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years. After i.v. dosing, the elimination half-life was 7.4±0.4 h, the total body clearance was 228±30 ml·min−1 and the volume of distribution at steady-state was 56±91. 72.5±4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16±2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance. The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance 〉90 ml·min−1) were similar to published data in young healthy male volunteers.
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  • 24
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    European journal of clinical pharmacology 35 (1988), S. 237-240 
    ISSN: 1432-1041
    Keywords: platelet activating factor (PAF) ; WEB 2086 ; platelet aggregation ; PAF-antagonist ; dose response ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary WEB 2086 is a novel PAF-acether antagonist, whose pharmacological action in man has only been preliminarily defined. Twelve healthy male volunteers received oral doses of 5, 30 and 90 mg and over the following 24 h inhibition of 5 × 10−8 M PAF-acether-induced platelet aggregation ex vivo was studied as an indicator of pharmacological activity. WEB 2086 inhibited PAF-acether-induced platelet aggregation in all the doses tested, with the maximum effect 1 to 2 h after administration. After 2 h 5- 30- and 90-mg doses caused, respectively, 87, 98 and 100% inhibition. The magnitude and duration of the inhibitory effect was dose-dependent, with a significant action still detectable 10 h after administration of all three doses, and 12 h after administration of the two highest doses (30 and 90 mg). The subjects did not complain of any significant adverse effect and all completed the study.
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  • 25
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    European journal of clinical pharmacology 35 (1988), S. 371-377 
    ISSN: 1432-1041
    Keywords: ACTH 4-10 ; radioimmunoassay ; plasma extraction ; pharmacokinetics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed. Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 µg/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39±0.05 min for the α-phase and 3.84 ± 1.5 min for the β-phase (mean±SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%). The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.
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  • 26
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    European journal of clinical pharmacology 35 (1988), S. 413-417 
    ISSN: 1432-1041
    Keywords: antipyrine ; acetaminophen ; lidocaine ; drug interactions ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received:1, antipyrine 1.0 g intravenously (i.v.);2, acetaminophen 650 mg i.v.;3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml·min−1·kg−1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen Vz was reduced (1.14 vs 1.00 l·kg−1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml·min−1·kg−1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine Vz (2.6 vs 2.7 l·kg−1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml·min−1·kg−1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine.
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  • 27
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    European journal of clinical pharmacology 35 (1988), S. 423-425 
    ISSN: 1432-1041
    Keywords: ketorolac tromethamine ; non-narcotic analgesic ; pharmacokinetics ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design. The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml·min−1·kg−1) and a small tissue distribution (Vss=0.111·kg−1, Vβ=0.17 l·kg−1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 µg/ml were rapidly attained (tmax = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.
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  • 28
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    European journal of clinical pharmacology 33 (1988), S. 619-624 
    ISSN: 1432-1041
    Keywords: propranolol ; isomers ; chronopharmacokinetics ; cardiovascular effects ; circadian changes ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Four subjects were synchronized with activity from 07 to 23 h and were given a single oral dose of 80 mg racemic propranolol at fixed times (08, 14, 20 and 02 h) at weekly intervals. ANOVA revealed significant circadian changes in the peak propranolol concentration (Cmax), with a maximum at 08 h and a minimum at 02 h after drug intake; tmax was not dependent on the circadian phase. The elimination half-life varied significantly with the time of day, being shortest at 08 h (3.3 h) and longest at 20 h (4.9 h). The stereospecificity of the propranolol pharmacokinetics was not dependent on the time of drug intake. No circadian variation was found in the maximum decrease in heart rate, but the time to peak effect was dependent on the time of drug intake; tmax was 2.3 h at 08 h and 7.0 h at 02 h. Thus, the time to peak drug concentration did not coincide with the time to peak effect on heart rate at different times of day. Circadian changes were also found in the systolic blood pressure and in the double product. The results show a significant daily variation in the pharmacokinetics and cardiovascular effects of propranolol. However, chronokinetics cannot explain the circadian changes in the effects of the drug. It is concluded that circadian variation in sympathetic tone and vascular reactivity is mainly responsible for the circadian changes in the effects of propranolol.
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  • 29
    ISSN: 1432-1041
    Keywords: flumazenil ; ethanol ; alcohol intoxication ; benzodiazepine antagonist ; interaction ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Flumazenil is a specific benzodiazepine antagonist. This study was designed to determine whether it also reverses CNS depression due to acute alcohol intoxication. Intoxication was experimentally induced in 6 healthy volunteers by intravenous infusion of ethanol. Individual constant ethanol plasma concentrations in the range 1.47±0.04 g · l−1 to 1.71±0.03 g · l−1 were maintained over 6 h. Two doses of flumazenil (0.1 or 0.2 mg · kg−1) and placebo were administered intravenously in a randomized, double-blind, two-way cross-over fashion. A battery of psychometric tests and subjective ratings of mood and performance were performed at baseline and at regular intervals during the study. Before the administration of flumazenil the characteristic symptoms and signs of ethanol intoxication were present in all subjects. Performance (measured by visual analogue scales), reaction time, digit symbol substitution test, and a tracing test, were markedly impaired by ethanol. After the injection of flumazenil three volunteers reported some subjective improvement in performance. However, in none of the subjects was there a difference between either dose of flumazenil and placebo in terms of an improvement in the objective psychometric variables.
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  • 30
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    European journal of clinical pharmacology 35 (1988), S. 563-566 
    ISSN: 1432-1041
    Keywords: tenoxicam ; pharmacokinetics ; elderly ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 µg·ml−1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 µg·ml−1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.
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  • 31
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    European journal of clinical pharmacology 35 (1988), S. 555-562 
    ISSN: 1432-1041
    Keywords: L-carnitine ; pharmacokinetics ; intravenous — oral doses ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet. Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 × h−1 (p〈0.025), thus showing dose-related elimination. Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively. Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.
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  • 32
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    European journal of clinical pharmacology 35 (1988), S. 607-612 
    ISSN: 1432-1041
    Keywords: propranolol ; atenolol ; baroreflex function ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute administration of the β-adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers. Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p〈0.05) to the left compared to placebo.
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  • 33
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    European journal of clinical pharmacology 35 (1988), S. 579-583 
    ISSN: 1432-1041
    Keywords: simvastatin ; bezafibrate ; hypercholesterolaemia ; LCAT ; lipoproteins ; serum cholesterol ; serum triglycerides ; side-effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen subjects with familial hypercholesterolaemia were randomly assigned to treatment with simvastatin 20–40 mg/day (an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase) or with bezafibrate 600 mg/day (a clofibrate analogue) for 12 weeks. Both drugs produced significant reductions in serum and LDL cholesterol; mean percentage fall −30.5% and −38.1% (simvastatin) and −17.8% and −20.6% (bezafibrate), respectively. Both drugs also caused a decrease in VLDL cholesterol, while only bezafibrate decreased the serum and VLDL triglyceride levels and increased HDL cholesterol and serum apolipoprotein A-I and A-II levels. Serum apolipoprotein B fell by 33.3% (simvastatin) and 15.7% (bezafibrate). Simvastatin and bezafibrate produced significant increases in the mean fractional esterification rate of LCAT, by +124,1% and +20.6%, respectively. Thus simvastatin was clearly more effective than bezafibrate in lowering LDL by enhancing its turnover, but bezafibrate had specific effects on VLDL and HDL that might be favourable in combined treatment regimens.
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  • 34
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    European journal of clinical pharmacology 35 (1988), S. 593-599 
    ISSN: 1432-1041
    Keywords: maprotiline ; nomifensine ; ethanol ; drug interaction ; echocardiography ; psychometry ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers received low doses of maprotiline and nomifensine up to 50 mg b. d. for 15 days in a double-blind, cross-over, placebo controlled study, during which echocardiography and psychomotor testing were carried out before and after the intake of alcohol 1 g/kg. Maprotiline increased heart rate and cardiac output and reduced peripheral resistance compared to placebo and nomifensine. Nomifensine alone was associated with a slight decrease in heart rate. Alcohol alone caused a significant increase in diastolic blood pressure, but did not otherwise modify the cardiovascular measures. The antidepressants did not augment the effects of alcohol. Antidepressants alone had no effect on psychomotor skills, but alcohol always impaired performance. No additional effects of alcohol were produced by the antidepressants. It appears that practically important peripheral or central consequences are unlikely to follow drinking a moderate amount of alcohol during regular therapy with low therapeutic doses of catecholamine reuptake inhibiting antidepressants. Experimental studies of the interaction of antidepressants and alcohol in patients with chronic heart disease seem to be justified.
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  • 35
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    European journal of clinical pharmacology 35 (1988), S. 631-635 
    ISSN: 1432-1041
    Keywords: enoximone ; heart failure ; inotropic activity ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and its sulphoxide metabolite, effects on the corrected electromechanical systole (QS2c), the impedance cardiogram (dZ/dt)/RZ index, blood pressure and heart rate were determined over an 8-h period. Peak effects on QS2c and the (dZ/dt)/RZ index were obtained after approximately 1 h. During the first hour, the cardiac effects lagged behind the high plasma concentrations. Thereafter, the effects on QS2c were closely correlated with the plasma concentrations both of enoximone and its sulphoxide derivative (r≥0.90). The concentration-effect curves of both substances were parallel and were independent of the route of administration. The inotropic activity was not related to the drug level in hypothetical peripheral compartments. The results suggest that determination of plasma enoximone 1 h after administration and thereafter may be useful in assessing the haemodynamic activity of the drug. Should this observation also be present in a clinical situation, plasma enoximone measurements might be a valuable tool in management of patients suffering from heart failure.
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  • 36
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    European journal of clinical pharmacology 35 (1988), S. 367-370 
    ISSN: 1432-1041
    Keywords: captopril ; pharmacokinetics ; healthy volunteers ; i.v. application
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic characteristics of intravenously-administered captopril were investigated in 7 healthy men 20 to 33 years old. Capropril, labeled with14C, was given by injection over a 1 min period at mean doses of 2.78 mg (13.8 µCi), 5.67 mg (28.2 µCi) and 11.4 mg (56.8 µCi). Concentrations of unchanged captopril, captopril disulfide, and other metabolites (collectively) were determined in body fluids. Pharmacokinetic parameters were calculated for unchanged captopril, and it was shown that the disposition of intravenously-administered drug was linear with respect to dose over the dosage range studied.
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  • 37
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    European journal of clinical pharmacology 35 (1988), S. 385-389 
    ISSN: 1432-1041
    Keywords: oxazepam ; pharmacokinetics ; i.v.-/oral administration ; bioavailability ; healthy volunteers
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2β) 6.7 h, total clearance (CL) 1.07 ml·min−1·kg−1, volume of distribution (Vc) 0.27 l·kg−1 (0.21–0.49) and volume of distribution at steady-state (Vss) 0.59 l·kg−1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5ml·min−1·kg−1 and a distribution volume of 12.3 l·kg−1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2β at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml·min−1·kg−1 (0.98–1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.
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  • 38
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    European journal of clinical pharmacology 33 (1988), S. 625-628 
    ISSN: 1432-1041
    Keywords: nadolol ; pharmacokinetics ; 14C-nadolol ; healthy volunteers ; i.v. administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To support the increasing use of intravenous β-blockers during cardiovascular emergency and surgery, dose proportionality of pharmacokinetics of nadolol was evaluated after intravenous administration of 14C-nadolol at doses of 1, 2 and 4 mg to nine healthy volunteers. There were no observed differences in the excretion or the pharmacokinetics of nadolol with respect to the dose administered. Over a 72-h period after drug administration, an average of about 60% of the dose was excreted in the urine and about 15% was excreted in the feces. The range of values for total body clearance (219 to 250 ml·min−1), renal clearance (131 to 150 ml·min−1), mean residence time (10.5 to 11.3 h), half-life (8.8 to 9.4 h), and steady-state volume of distribution (Vss) (147 to 157 l) indicated that nadolol was extensively distributed and slowly cleared from the body. There was a linear correlation (r 2=0.97) between the area under the plasma concentration of nadolol versus time curve (AUC) and the dose. All pharmacokinetics parameters, except Vss, were slightly, but significantly, different at the 4 mg dose. Superposition of the dose-normalized average concentrations indicated that despite these minor differences in parameters, the pharmacokinetic behavior of nadolol was linear with respect to dose. Urinary excretion of nadolol was dose independent.
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  • 39
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    European journal of clinical pharmacology 33 (1988), S. 643-645 
    ISSN: 1432-1041
    Keywords: ketoprofen ; food ; bioavailability
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketoprofen, a non-steroidal anti-inflammatory drug, in 12 patients after a single 100 mg oral dose both in fasting conditions and with a meal. Food significantly affected the peak plasma concentration of ketoprofen and decreased its absorption rate. However, the extent of absorption of ketoprofen, as reflected by the area under the plasma concentration time curve, appeared to be unchanged in the presence of food.
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  • 40
    ISSN: 1432-1041
    Keywords: cyclosporin ; pharmacokinetics ; infusions ; binding ; lipids ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary On the basis that unbound concentration better correlates with response than total plasma or blood concentration, the inter- and intra-subject variability in the distribution of cyclosporin within blood and to plasma components was studied in renal transplant patients. Pharmacokinetic aspects were also studied. Blood samples were analysed from patients who received the drug both by a 72-h i.v. infusion and orally (7 mg·kg−1 twice daily). Steady-state was reached within 18 h of starting the i.v. infusion; the plasma data were best fitted by a biexponential equation with half-times of 0.13–1.02 h and 4.3–13.9 h, associated with the two phases. The mean plasma clearance was 700 ml/min. Concentrations during the infusions measured by RIA and HPLC were comparable. Oral profiles showed rapid and extensive absorption. The peak plasma concentrations were 1460–1880 µg·l−1 and occurred 2–4 h after dosing, with bioavailability estimates of 41–113%. Concentrations measured by RIA were higher than by HPLC. Blood-to-plasma concentration ratio measurements of cyclosporin at 37°C decreased with increasing plasma concentration and increased with haematocrit. Fraction unbound, measured by ultracentrifugation, was in the range 0.042–0.122 with an average of 0.068, and varied little in some patients but showed systematic changes with time in others. Cyclosporin binding was found to be related not only to the triglyceride but, more particularly, to the cholesterol-related lipoproteins in plasma. Monitoring cholesterol may be helpful in identifying patients with extremes in binding or with widely varying binding.
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  • 41
    ISSN: 1432-1041
    Keywords: dilevalol ; hypertension ; labetolol R-R-isomer ; renal function ; plasma renin activity ; plasma aldosterone ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new β-adrenoceptor blocker with β2-receptor stimulating and α-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.
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  • 42
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    European journal of clinical pharmacology 35 (1988), S. 173-176 
    ISSN: 1432-1041
    Keywords: omeprazole ; pepsinogen ; serum pepsinogen A ; serum pepsinogen C ; gastric pepsin ; urinary pepsinogen A ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the effect of omeprazole on serum and urinary pepsinogens and on gastric pepsin, 8 healthy male volunteers were studied before and after 9 days of treatment with omeprazole 60 mg/day p.o. Fasting serum samples and 24 h urine specimens were obtained, and gastric contents were aspirated at 15-min intervals, 4 prior to and 6 during pentagastrin 1.5 µg·kg−1·h−1 i.v. during intra-gastric perfusion with NaCl 0.9% and phenol red 3 mg·ml−1 as an inert recovery marker. Basal and pentagastrin-stimulated volume and acid secretion were significantly decreased. The basal and pentagastrin stimulated pepsin output remained unchanged but pepsin concentration in gastric secretion was increased. Administration of omeprazole resulted in a significant increase in the serum PGA and PGC levels. The 24-h urinary excretion of PGA increased, but that of PGC remained unchanged, and so did the renal clearances of creatinine and pepsinogen A. The renal clearance of pepsinogen C decreased. It was concluded that omeprazole did not affect gastric pepsin output, but, due to the decreased volume output, the concentration of pepsin in the gastric secretion was increased. Omeprazole increased the serum levels of pepsinogen A and C because more pepsinogen was released into the systemic circulation. This might be due to greater back-diffusion of pepsinogen from the gastric mucosa into the systemic circulation as a result of the higher pepsinogen concentration in gastric secretion.
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  • 43
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    European journal of clinical pharmacology 35 (1988), S. 221-223 
    ISSN: 1432-1041
    Keywords: sertraline ; antidepressants ; critical flicker fusion ; psychopharmacology ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, placebo controlled, cross-over study was carried out in 10 normal healthy volunteers to investigate the effects of sertraline 25 mg, 50 mg, 75 mg and 100 mg on aspects of cognitive functioning. Changes with respect to placebo in objective tests of psychomotor function (critical flicker fusion and choice reaction time) showed that sertraline had an alerting effect. The changes were not consistent with subjective reports of drowsiness.
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  • 44
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    European journal of clinical pharmacology 34 (1988), S. 363-368 
    ISSN: 1432-1041
    Keywords: bisoprolol ; propranolol ; beta-adrenergic blockade ; atropine ; exercise testing ; ethnic differences ; healthy volunteers ; autonomic tone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A randomized, double-blind, placebo-controlled study was performed in 8 white and 8 black volunteers matched for sex, age and mass. The effect of 3 intravenous doses of a new, cardiose-lective beta-adrenergic blocker, bisoprolol, on the heart rate increase after standardized exercise was compared to that of 3 doses of propranolol. As described previously for propranolol, black volunteers showed less response than whites to beta-blockade assessed in terms of the reduction in exercise-induced tachycardia. The effects of the two beta-blockers were similar and the apparent ethnic difference was seen with both drugs. It has previously been shown that black volunteers have a higher intrinsic heart rate (i.e. heart rate after parasympathetic and beta-adrenergic blockade of the heart) than whites, but their resting heart rates are similar because of greater parasympathetic tone in blacks. When exercise-load was calculated as increase in heart rate above that after atropinization, no ethnic differences were seen. It is suggested that in populations that are heterogenous in terms of the heart rate increase after atropine, work load should be standardized in terms of the increase in heart rate over the atropine heart rate rather than on absolute heart rate. The apparent ethnic difference represents a flaw in methodology as applied to a heterogenous volunteer population.
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  • 45
    ISSN: 1432-1041
    Keywords: oxprenolol ; beta-blockade ; concentration-effect relationship ; non-invasive monitoring ; exercise test ; blood pressure monitoring ; healthy volunteers ; predictive model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentration of oxprenolol and its haemodynamic effects during physical exercise was studied in 6 healthy volunteers, in whom BP and heart rate (HR) were continuously monitored by non-invasive techniques (Fin-A-Press-Tonometer) during repeated three-minute exercise periods for 8 h after treatment. Using the fitted pharmacokinetic curve, the drug effect was related to its plasma concentration using the Emax model. The mean EC50 for the relationship between drug concentration and heart rate during exercise (HRex) was 73.1 ng/ml, and for systolic blood pressure during exercise (SBPex) it was 112.7 ng/ml. Emax was 29.0% for HRex, and 33.2% for SBPex. There were no consistent differences between the parameters for the effects on HRex and SPBex. Thus, using a new, non-invasive technique for continuous measurement of blood pressure, the effect of a beta-adrenoceptor blocking drug on SBPex was described with similar accuracy as its effect on HRex.
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  • 46
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    European journal of clinical pharmacology 34 (1988), S. 601-604 
    ISSN: 1432-1041
    Keywords: cyclosporin A ; uveitis ; renal function ; creatinine clearance ; hypertension ; corticosteroids ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal function has been evaluated in 21 patients treated with cyclosporin A (CyA) for 9 months for idiopathic uveitis. Serum creatinine, which was 82 µmol·l−1 before treatment, was significantly elevated after 1 month (111 µmol·l−1). After 9 months of treatment, and despite a decrease in CyA dosage, the mean plasma creatinine remained elevated at 132 µmol·l−1. Hypertension developed in 6 patients, five of them being concomitantly treated with corticosteroids. In 8 patients serum creatinine 3 months after CyA had been stopped had decreased from 148 to 93 µmol·l−1. Two of those patients remained hypertensive 3 months after CyA treatment had ceased. In patients with idiopathic uveitis CyA induces a reversible increase in serum creatinine. However the reversibility of such a biochemical marker does not preclude a histopathological lesion. Chronic renal damage may be responsible for the persistance of hypertension after cessation of CyA treatment
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  • 47
    ISSN: 1432-1041
    Keywords: adinazolam ; cimetidine ; pharmacokinetics ; pharmacodynamics ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration. Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments. Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life. The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine. Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.
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  • 48
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    European journal of clinical pharmacology 35 (1988), S. 85-88 
    ISSN: 1432-1041
    Keywords: ibuprofen ; nizatidine ; cimetidine ; drug interaction ; pharmacokinetics ; healthy volunteers ; H2-antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The potential for interaction between ibuprofen and two histamine H2-receptor blocking drugs — nizatidine and cimetidine — was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man.
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  • 49
    ISSN: 1432-1041
    Keywords: fluocortolone ; cortisol ; alternate day therapy ; plasma cortisol ACTH ; plasma level ; healthy volunteers ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of fluocortolone and its effect on the circadian rhythm of plasma cortisol and ACTH have been studied during different schedules of oral administration. Groups of 6 healthy male adults were given a single daily dose of fluocortolone 5, 10 and 20 mg, and another group received 20 mg every second day. Administration to all groups was continued for 8 days. Pharmacokinetic parameters of fluocortolone (half lives of absorption- t1/2a and elimination t1/2e, volume of distribution V and oral clearance (CL/f) were independent of the duration of treatment and dose. Areas under the plasma level curves, AUC and Cmax values increased in proportion to the dose, indicating dose linearity of fluocortolone pharmacokinetics. A normal morning cortisol peak occurred during all treatment schedules, which indicates that circadian cortisol secretion was not seriously affected by the glucocorticoid treatment. On the other hand, when the level of circulating fluocortolone was high the 12.00 a.m. and 4.00 p.m. cortisol levels were diminished compared to the pre and posttreatment values. There was no definite correlation between the ACTH and cortisol levels, either on treatment or on control days. ACTH levels were suppressed by daily treatment with the 20 mg dose. Thus, even during administration of a high dose of a glucocorticoid, the circadian secretion of cortisol can be preserved if the treatment is adjusted according to the half-life of the drug.
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  • 50
    ISSN: 1432-1041
    Keywords: xamoterol ; partial agonist ; beta1-selective ; physical performance ; metabolism ; healthy volunteers ; hormone levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, random, cross-over study, 14 healthy male volunteers received xamoterol 200 mg (Corwin; C) twice daily or placebo (P) for two seven-day medication periods to investigate effects on physical performance, cardiocirulatory parameters, metabolism and hormone levels during exercise. An oral glucose tolerance test (OGTT) was also done. C showed a positive inotropic effect up to an exercise intensity of 100 W, corresponding to a heart rate of about 100 beats · min−1. Chronotropic regulation of the heart remained unchanged, but the increase in systolic blood pressure was more pronounced and the catecholamines behaved as after P. From 150 W onwards, C exhibited beta-blocking properties; heart rate was reduced by up to 8 beats · min−1; systolic blood pressure remained unchanged; and the catecholamines showed a more pronounced increase than after P. Diastolic blood pressure behaved almost identically under all test conditions. With the exception of a slightly increased level of free fatty acids at rest, the parameters of physical performance, lipid and carbohydrate metabolism and the hormone levels under all conditions after C showed similar behaviour to that after as P. The findings indicate that physical performance capacity, cardiocirculatory system, metabolism and hormones were not negatively influenced by C.
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  • 51
    ISSN: 1432-1041
    Keywords: cimetidine ; ramixotidine ; prolactin ; testosterone ; 17 beta-estradiol ; H2-receptors ; CM 57755A ; gastrin ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17β-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.
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  • 52
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    European journal of clinical pharmacology 35 (1988), S. 535-541 
    ISSN: 1432-1041
    Keywords: bromocriptine ; pharmacokinetics ; food interaction ; modified release formulation ; prolactin inhibition ; pharmacodynamics ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolaction over 36 h, in all subjects, both fasted and after a meal.
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  • 53
    ISSN: 1432-1041
    Keywords: ivermectin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Administration of 12-mg doses of ivermectin (H2B1a) to 12 healthy volunteers in the form of tablets, capsules, and alcoholic oral solution showed the solution to have approximately twice the systemic availability as either of the solid forms, as evidence both by the maximum concentrations of drug attained in plasma and by the corresponding areas under the plasma concentration vs time curves. However, the two solid formulations showed similar systemic availability.
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  • 54
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; infarct prevention ; platelet aggregation ; pharmacokinetics ; healthy volunteers ; secondary heart attack prevention ; AMIS ; PARIS ; German-Austrian trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.
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  • 55
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    Molecular and cellular biochemistry 82 (1988), S. 67-73 
    ISSN: 1573-4919
    Keywords: neurotransmitter control ; secretion ; exocrine ; salivary gland ; calcium ; ATP-dependent calcium transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary gland fluid secretion following neurotransmitter stimulation is Ca2+-dependent. We have studied the control of cellular Ca2+ following secretory stimuli in rat parotid gland acinar cells. After muscarinic-cholinergic receptor activation, cytosolic Ca2+ is elevated 4–5 fold, due to both intracellular Ca2+ pool mobilization and extracellular Ca2+ entry. Fluid movement ensues due to the Ca2+-activated enhancement of membrane permeability to K+ and Cl−. Basal cytosolic Ca2+ levels are tightly controlled at ∼150–200 nM through the action of high affinity and high capacity ATP-dependent Ca2+ transporters in the basolateral and endoplasmic reticulum membranes. Activity of these Ca2+ transporters can be modulated to facilitate rapid responsiveness and a sustained fluid secretory response necessary for alimentary function.
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  • 56
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    Molecular and cellular biochemistry 84 (1988), S. 97-103 
    ISSN: 1573-4919
    Keywords: neutrophils ; A23187 ; lasalocid ; calcium ; superoxide ; chemotactic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Effects of Ca2+ ionophores, A23187 and lasalocid, on superoxide anion generation by chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine methyl ester, in rabbit peritoneal exudate neutrophils were studied. The ionophores by themselves did not activate superoxide anion generation in these neutrophils. When preincubated with the cells for 2 min, both the ionophores inhibited superoxide generation induced by chemotactic peptide. The inhibition was present even in the absence of extracellular Ca2+ and the inhibition was better then. Lasalocid produces a dose-dependent chlortetracycline fluorescence decrease response in neutrophils loaded with chlortetracycline. This response is independent of extracellular Ca2+ concentration and is related to release of Ca2+ from intracellular storage sites. The dose-range at which lasalocid gives this response is same as the dose-range at which it causes inhibition of superoxide response. It may be concluded that the inhibition of superoxide generation by these ionophores is correlated to intracellular Ca2+ modulation.
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  • 57
    ISSN: 1573-4919
    Keywords: bladder ; muscarinic stimulation ; metabolism ; bethanecol ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The calcium dependence of contraction and NADH flurorescence was investigated in rabbit bladder stimulated with bethanechol or KCl. The absence of calcium in the bathing solution induced a rightward shift in the dose response to bethanechol for both contraction and NADH flurorescence. The contractile response was shifted to a greater degree than the fluorescence response and the maximal response to bethanechol was reduced by 80% for contraction but only 20% for NADH fluorescence. This rightward shift was also induced by the benzothiazepine calcium antagonist diltiazem (200 μM) and again the contractile response was shifted significantly more than the fluorescence response. The combination of zero calcium and 200 μM diltiazem virtually abolished contractions but only inhibited the NADH fluorescence by 65% at maximally effective bethanechol concentrations. Unlike the effect of diltiazem on the response to bethanechol, diltiazem (200 μM) shifted both the contraction and fluorescence curves to the right equally in response to KCl stimulation. These results indicate that a metabolic response to muscarinic stimulation (decreased NADH) can occur in the absence of any observable contractile response. This metabolic response may be due to post receptor signal processing events. For KCl stimulation, the NADH response is probably secondary to and a result of the contractile response.
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  • 58
    ISSN: 1573-1561
    Keywords: Electroantennogram ; pheromone ; bark beetles ; Ips, Dendroctonus ; Coleoptera ; Scolytidae ; olfactory receptors ; intraspecific ; interspecific ; electrophysiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Electroantennograms (EAGs) from male and femaleIps avulsus, I. calligraphus, andI. grandicollis to their pheromones and selected host odorants or kairomones verified the presence of antennal olfactory receptors in both sexes of each species capable of detecting ipsdienol, ipsenol,cis- andtrans-verbenol,endo-brevicomin α-pinene, frontalin, and verbenone. Each species possesses receptors with lower thresholds and in greater abundance for the compounds they produce and to which they are behaviorally most responsive. Detection of bothIps andDendroctonus pheromones by the three cohabiting species provides a sensory basis for olfactory interactions among the species. Differences in both threshold and saturation levels for EAGs for the various behavioral chemicals could denote differences in specific behavioral roles for each compound.
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  • 59
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    Journal of chemical ecology 14 (1988), S. 2071-2098 
    ISSN: 1573-1561
    Keywords: Grain beetles ; Coleoptera ; Cucujidae ; Cathartus quadricollis ; Cryptolestes ferrugineus ; C. pusillus ; C. turcicus ; Oryzaephilus mercator ; O. surinamensis ; macrolide aggregation pheromone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Males of five sympatric species of economically damaging cucujid grain beetles,Cryptolestes ferrugineus (Stephens),C. pusillus (Schönhen),C. turcicus (Grouvelle),Oryzaephilus mercator (Fauvel), andO. surinamensis (L.), produce macrolide aggregation pheromones especially in the presence of food. Work leading to the isolation, identification, and establishment of biological activity of these semiochemicals is reviewed. The trivial name “cucujolide” is proposed and used to identify these compounds that are characteristic of the Cucujidae. The twoOryzaephilus share species share a common cucujolide pheromone, whileCryptolestes species use cucujolides that are either enantiomeric, unique to the genus, or released in trace quantities byOryzaephilus spp. and not used as pheromones by the latter species. The major mechanisms for species specificity in chemical communication are: (1) presence of a unique pheromone (C. ferrugineus andC. pusillus); (2) use of pheromones that are inactive alone but synergize response to cucujolides unique to a species (C. pusillus, C. turcicus, andO. surinamensis); (3) response to only one enantiomer of a pheromone (C. ferrugineus, O. surinamensis, andO. mercator); and (4) synergism between enantiomers of a pheromone (C. turcicus). The only species for which cross-attraction was evident wasO. mercator toO. surinamensis. Both sexes ofOryzaephilus spp. produce (R)-1-octen-3-ol, which highly synergizes response to the cucujolide pheromones. Similar synergism occurs between hexanal, octanal, and nonanal and the cucujolide pheromones ofOryzaephilus spp. The males of a sixth cucujid species,Cathartus quadricollis (Guér) produce a different aggregation pheromone, (3R,6E)-7-methyl-6-nonen-3-yl acetate. Trapping ofCryptolestes andOryzaephilus spp. in cardboard traps baited with pheromones is efficient in environments mimicking food-storage areas. Pheromone-baited plastic probe traps are the most efficient at capturing these species in infested grain.
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  • 60
    ISSN: 1573-1561
    Keywords: Cathartus quadricollis (Guér.) ; square-necked grain beetle ; Coleoptera ; Cucujidae ; aggregation pheromone ; (3R,6E)-7-methyl-6-nonen-3-yl acetate ; (E)-7-methyl-6-nonen-3-one ; (E)-7-methyl-6-nonen-3-ol ; (6E)-7-methyl-3-propyl-2,6-nonadienyl acetate ; 1-octen-3-ol ; repellent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract When feeding on rolled oats, male square-necked grain beetles,Cathartus quadricollis (Guér.), produced the aggregation pheromone (3R,6E)-7-methyl-6-nonen-3-yl acetate, for which the trival name “quadrilure” is proposed. The pheromone was highly attractive to both sexes in a two-choice, pitfall olfactometer modified to retain responding beetles by placing a food stimulus (an oat flake) in the glass vials containing the experimental and control stimuli. TheS enantiomer of the pheromone was inactive. Males also produced small amounts of (E)-7-methyl-6-nonen-3-one, (E)-7-methyl-6-nonen-3-ol, and (6E)-7-methyl-3-propyl-2,6-nonadienyl acetate, but these compounds were inactive in the laboratory bioassay. Segregated males and females both produced (R)-(−)-1-octen-3-ol, which by itself was repellent to both sexes but did not diminish beetle response to the aggregation pheromone.
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  • 61
    ISSN: 1573-1561
    Keywords: Dendroctonus ponderosae ; Coleoptera ; Scolytidae ; pheromones ; trans-verbenol ; ipsdienol ; allelochemicals ; mixed-function oxidases ; monooxygenase inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Female and male mountain pine beetles,Dendroctonus ponderosae Hopkins, were treated topically with piperonyl butoxide or sesame oil, both of which are known to inhibit poly substrate monooxygenase activity. Beetles then exposed to vapors of the host monoterpenes α-pinene and myrcene were found to contain reduced levels of the pheromonestrans-verbenol and ipsdienol, as well as a buildup of monoterpene precursors. Polysubstrate monooxygenase enzymes appear to be at least partially responsible for the detoxification of host monoterpenes and for the production of terpene alcohol pheromones in this species.
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  • 62
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    Journal of chemical ecology 14 (1988), S. 635-651 
    ISSN: 1573-1561
    Keywords: Rootworm adults ; Diabrotica spp. ; Coleoptera ; Chrysomelidae ; attraction ; corn ; flight tunnel ; ethograms ; host finding ; bioassay
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Volatile chemicals from corn silks attractedDiabrotica virgifera virgifera LeConte andD. barberi (Smith and Lawrence). The behavioral response of both species of beetles to the host plant was typified by four distinct phases: perception, random movement, orientation to the source, and search with reorientation. The perception phase was composed of stationary behaviors, while the random, orientation, and search phases were composed of directed and nondirected movements. Each of the movement phases had a characteristic response pattern composed of the ratio of upwind, lateral, and downwind walking and flight movements, which affected net displacement of the beetle in the flight tunnel. The perception phase occurred within and between the other phases and was responsible for initiating changes from one movement phase to another (based on the presence or absence of volatiles from corn silks). Host finding was flexible, and the response pattern fit a flow-chart type of response, rather than a single stereotyped sequence of behaviors.
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  • 63
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    Bioscience reports 8 (1988), S. 579-583 
    ISSN: 1573-4935
    Keywords: calcium ; zinc ; membrane protection
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Certain cytotoxic agents damage cells by the induction of pores across their plasma membrane. Ca2+ and Zn2+ protect against such damage by promoting pore closure. Zn2+ may play a beneficial role in this regard in certain disease states.
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  • 64
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    Bioscience reports 8 (1988), S. 27-33 
    ISSN: 1573-4935
    Keywords: cystic fibrosis ; chloride transport ; exocytosis ; calcium ; calmodulin ; B-adrenergic ; cyclic AMP
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A biochemical link is proposed between recent observations on defective regulation of Cl− transport in CF respiratory epithelial cells and studies showing altered biological activity of calmodulin in exocrine glands from CF patients. A consensus is emerging that defective β-adrenergic secretory responsiveness in CF cells is caused by a defect in a regulator protein at a site distal to cyclic AMP formation. Our results indicate that this protein might be a specific calmodulin acceptor protein which modifies the activity of calmodulin in epithelial cells. Alteration in Ca2+/calmodulin dependent regulation of Cl− transport and protein secretion could explain (i) alterations in Ca2+ homeostasis seen in CF, (ii) defective β-adrenergic responses of CF cells, and (iii) the observed inability of cyclic AMP (acting via its specific protein kinase, A-kinase) to open apical membrane Cl− channels in CF epithelial cells. Most of the physiological abnormalities of CF including elevated sweat electrolytes and hyperviscous mucus can be explained on this basis.
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  • 65
    ISSN: 1573-4935
    Keywords: calcium ; exocytosis ; sea urchin egg ; phosphoinositide ; diacylglycerol
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Micromolar calcium ion concentrations stimulate exocytosis in a reconstituted system made by recombining in the plasma membrane and cortical secretory granules of the sea urchin egg. The isolated cortical granules are unaffected by calcium concentrations up to 1 mM, nor do granule aggregates undergo any mutual fusion at this concentration. Both isolated plasma membrane and cortical granules can be pretreated with 1 mM Ca before reconstitution without affecting the subsequent exocytosis of the reconstituted system in response to micromolar calcium concentrations. On reconstitution, aggregated cortical granules will fuse with one another in response to micromolar calcium provided that one of their number is in contact with the plasma membrane. If exocytosis involves the generation of lipid fusogens, then these results suggest that the calcium-stimulated production of a fusogen can occur only when contiguity exists between cortical granules and plasma membrane. They also suggest that a substance involved in exocytosis can diffuse and cause piggy-back fusion of secretory granules that are in contact with the plasma membrane. Our results are also consistent with a scheme in which calcium ions cause a reversible, allosteric activation of an exocytotic protein.
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  • 66
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    The journal of membrane biology 105 (1988), S. 207-219 
    ISSN: 1432-1424
    Keywords: choroid plexus ; brush border membrane ; Ca2+-activated K+ channels ; calcium ; barium ; TEA ; intracellular pH ; cerebrospinal fluid secretion
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The properties of Ca2+-activated K+ channels in the apical membrane of theNecturus choroid plexus were studied using single-channel recording techniques in the cell-attached and excised-patch configurations. Channels with large unitary conductances clustered around 150 and 220 pS were most commonly observed. These channels exhibited a high selectivity for K+ over Na+ and K+ over Cs+. They were blocked by high cytoplasmic Na+ concentrations (110mm). Channel activity increased with depolarizing membrane potentials, and with increasing cytoplasmic Ca2+ concentrations. Increasing Ca2+ from 5 to 500nm, increased open probability by an order of magnitude, without changing single-channel conductance. Open probability increased up to 10-fold with a 20-mV depolarization when Ca2+ was 500nm. Lowering intracellular pH one unit, decreased open probability by more than two orders of magnitude, but pH did not affect single-channel conductance. Cytoplasmic Ba2+ reduced both channel-open probability and conductance. The sites for the action of Ba2+ are located at a distance more than halfway through the applied electric field from the inside of the membrane. Values of 0.013 and 117mm were calculated as the apparent Ba2+ dissociation constants (K d (0 mV) for the effects on probability and conductance, respectively. TEA+ (tetraethylammonium) reduced single-channel current. Applied to the cytoplasmic side, it acted on a site 20% of the distance through the membrane, with aK d (0 mV)=5.6mm. A second site, with a higher affinity,K d (0 mV)=0.23mm, may account for the near total block of chanel conductance by 2mm TEA+ applied to the outside of the membrane. It is concluded that the channels inNecturus choroid plexus exhibit many of the properties of “maxi” Ca2+-activated K+ channels found in other tissues.
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  • 67
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    The journal of membrane biology 105 (1988), S. 221-231 
    ISSN: 1432-1424
    Keywords: choroid plexus ; calcium-activated potassium currents ; cerebrospinal fluid secretion ; calcium ; delayed currents ; patch clamp
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The tight-seal whole-cell recording method has been used to studyNecturus choroid plexus epithelium. A cell potential of −59±2 mV and a whole cell resistance of 56±6 MΩ were measured using this technique. Application of depolarizing step potentials activated voltage-dependent outward currents that developed with time. For example, when the cell was bathed in 110mm NaCl Ringer solution and the interior of the cell contained a solution of 110mm KCl and 5nm Ca2+, stepping the membrane potential from a holding value of −50 to −10 mV evoked outward currents which, after a delay of greater than 50 msec, increased to a steady state in 500 msec. The voltage dependence of the delayed currents suggests that they may be currents through Ca2+-activated K_ channels. Based on the voltage dependence of the activation of Ca2+-activated K+ channels, we have devised a general method to isolate the delayed currents. The delayed currents were highly selective for K+ as their reversal potential at different K+ concentration gradients followed the Nernst potential for K+. These currents were reduced by the addition of TEA+ to the bath solution and were eliminated when Cs+ or Na+ replaced intracellular K+. Increasing the membrane potential to more positive values decreased both the delay and the half-times (t 1/2) to the steady value. Increasing the pipette Ca2+ also decreased the delay and decreasedt 1/2. For instance, when pipette Ca2+ was increased from 5 to 500nm, the delay andt 1/2 decreased from values greater than 50 and 150 msec to values less than 10 and 50 msec. We conclude that the delayed currents are K+ currents through Ca2+-activated K+ channels. At the resting membrane potential of −60 mV, Ca2+-activated K+ channels contribute between 13 to 25% of the total conductance of the cell. The contribution of these channels to cell conductance nearly doubles with membrane depolarization of 20–30 mV. Such depolarizations have been observed when cerebrospinal fluid (CSF) secretion is stimulated by cAMP and with intracellular Ca2+. Thus the Ca2+-activated K+ channels may play a specific role in maintaining intracellular K+ concentrations during CSF secretion.
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  • 68
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    The journal of membrane biology 101 (1988), S. 199-207 
    ISSN: 1432-1424
    Keywords: exocytosis ; membrane fusion ; secretion ; calcium ; sea urchin egg ; cortical granule
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary We study exocytosis in the planar isolated cortex of the egg of the sea urchinLytechinus pictus. Solutins bathing the exocytotic apparatus need not contain appreciable amounts of ions: fusion follows addition of submicromolar calcium to solutions containing only nonelectrolyte. We examine the effects of altering the granule membrane permeability to small molecules with ionophores and digitonin. Introducing holes in the secretory granule membrane to the extent of allowing free passage of small molecules does not cause seretion in vitro. We add the amphipathic compound digitonin at 12 to 15 μM concentrations and demonstrate that the granule membrane can become permeable to lucifer yellow, yet that granules remain intact. Granules still undergo exocytosis after digitonin treatment at such concentrations upon subsequent addition of calcium. Higher concentrations of digitonin lead to granule content swelling and vesicle bursting. We conclude that cortical granule hydration during exocytosis is not mediated by small ionic channels.
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  • 69
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    The journal of membrane biology 101 (1988), S. 33-41 
    ISSN: 1432-1424
    Keywords: electric current ; protons ; Neurospora crassa ; pH gradient ; H+-ATPase ; calcium
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Hyphae ofNeurospora crassa, like many other tipgrowing organisms, drive endogenous electric currents through themselves such that positive charges flow into the apical region and exit from the trunk. In order to identify the ions that carry the current, the complete growth medium was replaced by media lacking various constituents. Omission of K+ or of phosphate diminished the zone of inward current, effectively shifting the current pattern towards the apex. Omission of glucose markedly reduced both inward and outward currents; addition of sodium azide virtually abolished the flow of electric current. Growing hyphae also generate a longitudinal pH gradient: the medium surrounding the apex is slightly more alkaline than the bulk phase, while medium adjacent to the trunk turns acid. The results suggest thatNeurospora hyphae generate a proton current; protons are expelled distally by the H+-ATPase and return into the apical region by a number of pathways, including the symport of protons with phosphate and potassium ions. Calcium influx may also contribute to the electric current that enters the apical region. There seems to be no simple obligatory linkage between the intensity of the transcellular electric current and the rate of hyphal extension. Calcium ions, however, are required in micromolar concentrations for extensions and morphogenesis of hyphal tips.
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  • 70
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    The journal of membrane biology 104 (1988), S. 21-34 
    ISSN: 1432-1424
    Keywords: exocytosis ; secretion ; calcium ; protein kinase C ; adrenal medulla ; catecholamine
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    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The calcium sensitivity of exocytosis from electroper-meabilized chromaffin cells is increased by activators of protein kinase C, such as TPA and certain phorbol esters, diacylglycerols, and mezerein. A range of putative inhibitors of protein kinase C block both the phorbol ester-sensitive component of secretion and also the underlying insensitive component. These inhibitors are also shown to inhibit medulla protein kinase C activity in vitro. The extent of secretion is reduced when electropermeabilized cells are exposed to Ca2+ levels much in excess of 50 μm. The onset of inhibition is faster than the relatively slow rate of Ca-dependent exocytosis and is insensitive to inhibitors of proteolysis. Adrenal medulla protein kinase C activity is also irreversibly inhibited by high Ca2+ concentrations. Both the secretory response and the protein kinase C activity in vitro have similar nucleotide and cation specificities. Although these data do not definitely establish an involvement of protein kinase C in exocytosis, none argue against it.
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  • 71
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    Chromatographia 25 (1988), S. 31-36 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Radioactivity detector ; Solid scintillator ; Fibre-packed flow cells
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    Topics: Chemistry and Pharmacology
    Notes: Summary A new type of flow-cell radiation detector for use in liquid chromatography which is packed with aligned scintillator fibers is described. A primary advantage of the fiber packed cell is that light generated by the scintillator is absorbed to a much less extent by the fibers than by the powder scintillator used in conventional flow cells. A detection efficiency of 55% has been obtained for carbon-14 using 0.1-mm diameter hand-pulled glass fibers. Computer modeling has shown that even better results can be obtained by using smaller and more uniform diameter fibers which will allow better packing. The fiber cell also demonstrates back pressures which are a factor of 50 less than the conventional cell and much less susceptibility to absorption of compounds because of its lower surface area.
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  • 72
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    Chromatographia 25 (1988), S. 854-860 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Polystyrene ; Gradient elution ; Turbidimetry
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    Topics: Chemistry and Pharmacology
    Notes: Summary Polystyrene samples of narrow molecular-weight distribution have been eluted according to their molecular weight from columns packed with bare silica Si50, phenyl, or C18 bonded phase by gradients of methanol and tetrahydrofuran (THF) or ofiso-octane and THF. Among the six combinations investigated,iso-octane/THF with a silica column formed a proper normal-phase system whereas methanol/THF with a C18 column formed a proper reversed-phase system. The combinations of C18 column andiso-octane/THF or of Si50 column and methanol/THF gradient did not correspond to the approved polarity rules in high-performance liquid chromatography but were nevertheless effective in separating polystyrene mixtures by molecular weight. Methanol andiso-octane are nonsolvents for polystyrene whereas THF is a solvent. The solubility of polystyrene as a function of molecular weight and concentration was determined by means of turbidimetric titration of solutions in THF with the nonsolvents used in the gradients. The solubility and elution characteristics were almost identical on C18 columns or in methanol/THF combinations. The elution from phenyl bonded phase and Si50 columns usingiso-octane/THF gradients required more THF than the solubility experiments. Information is also given on the occurrence of multimodal elution patterns.
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  • 73
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Polycyclic aromatic compounds ; Alkylated PAC ; Retention characteristics ; Normal phase
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    Topics: Chemistry and Pharmacology
    Notes: Summary Retention characteristics of series of polymethyl and mono-n-alkyl derivatives of benzene and pyrene, and also of parent polycyclic aromatic hydrocarbons (PAH), were studied using silica and aminopropyl- and cyanopropyl-modified silica. Differences in the selectivities for the studied compound groups were found between the three phases. Deviations from linear behaviour in plots of log (k′)vs. carbon number were observed for the methyl series. These are explained in terms of differences in π-electron delocalisation within the aromatic ring systems. Further, the effect of methyl substitution on selectivity decreased with an increasing number of aromatic rings. Results were obtained which indicated that the primary adsorption site in a cyano column used in normal phase mode, at least for PAH molecules, is the cyano group.
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  • 74
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    Chromatographia 25 (1988), S. 43-50 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Reversed phase ; Void volume ; Adsorption isotherms
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    Topics: Chemistry and Pharmacology
    Notes: Summary In reversed-phase liquid chromatography with n-alkyl bonded silica, the dead volume (V0) of the column is theoretically indeterminate owing to adsorption of organic modifier on n-alkyl chains and of water on silanol groups. With binary mobile phases, retention volumes of the mobile phase components and of their deuterated species are relaeed to the adsorption isotherms and V0 by equations which can be solved with some assumptions on the adsorbed layer composition. Methanol-water and acetonitrile-water systems are studied. As the experimental excess isotherm shows a linear part in the concentration range 50–80% in organic modifier, the hypothesis of an adsorbed layer of constant composition in this range is possible. When increasing the water content of the mobile phase, adsorption of water occurs up to saturation of silanol groups. Then the assumption of a constant water content for a mobile phase having more than 50% of water is applied. With the hypothesis of a constant adsorbed content of organic modifier when the eluent has more than 80% of organic modifier, V0 and the absolute isotherms are calculated over the entire range of mobile phase composition. Experimental retention behavior of the mobile phase components are totally explained by these V0 determinations. The retention times of commonly used V0 markers are compared with V0 values. It is shown that, when buffering the eluent, no visible effect on the distribution equilibrium is observed, so that injection of concentrated potassium nitrate is a convenient method to measure V0. With a few solutes with are UV detectable it is possible to measure V0 whatever the mobile phase composition in methanol-water and acetonitrile-water systems.
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  • 75
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Stationary phase solubility parameters ; Cyano-silica ; Amino-silica ; Diol-silica
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    Topics: Chemistry and Pharmacology
    Notes: Summary Extended solubility parameters have been determined for aminopropyl, cyanopropyl and 1,2-dihydroxypropyl propyl ether (diol) normal bonded-phase HPLC columns. Parameters were calculated from both the retention data of solutes (partition model) and empirically determined solvent strengths (adsorption-displacement model). The use of solvent strengths to calculate solubility parameters for these silica-based bonded stationary phases appears to be superior, since this technique avoids many of the problems that arise from their inherent heterogeneity. Normalized solubility parameters were also used to position these columns on a stationary phase selectivity triangle. The amino and cyano phases appear in regions of the tringle expected based on the properties of the pure liquids, but an ether linkage in the diol apparently neutralizes some of the acidity expected from this phase.
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  • 76
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Macrolide antibiotic azithromycin ; Intermediates of azithromycin ; Optimization of separation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary HPLC is the most convenient method for the assay of the azithromycin (10-dihydro-10-deoxo-11-methyl-11-azaerythromycin A), a semisynthetic macrolide antibiotic and its reaction intermediates. Data concerning the effects of pH, temperature and column type are presented. The analytical procedures enabling the reliable assay of azithromycin and its intermediates, as well as other impurities are defined. Use of a reversed-phase octadecyl column, a pH of 9.3–9.5, and isocratic mode at ambient temperature are the best conditions of analysis.
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  • 77
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Metabolic disorders ; Xanthine and 2,8-dihydroxyadenine ; Urine analysis
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    Topics: Chemistry and Pharmacology
    Notes: Summary 2,8-Dihydroxyadeninuria and xanthinuria are inborn enzyme disorders which must be under lifelong therapeutic control. Quantitative determination of 2,8-DHA and xanthine using reversed phase HPLC was performed. A new application for the separation of purines shortens analysis-time. Examples of the determination of 2,8-DHA and xanthine before and under certain therapies are shown. Long term monitoring of the patients offers the possibility of a reliable prophylaxis against stone recurrence.
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  • 78
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Indirect detection of non-electrolytes ; Simulation of induced peaks ; RP systems
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    Topics: Chemistry and Pharmacology
    Notes: Summary Induced peaks observed in indirect detection of nonelectrolytes in high-performance liquid chromatography are simulated. The equation representing the signal intensity of the induced peaks is derived, and it is verified by the experimental results. The peak area is proportional to (K b ′ +1) k a ′ /| a ′ —k b ′ |, where k a ′ ad k b ′ are the capacity factors of the visualization agent and the analyte, respectively.
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  • 79
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    Chromatographia 25 (1988), S. 162-166 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Ion chromatography ; Analysis of metal ions ; Post column derivatisation ; Amperometric detection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A method for determination of metal ions subsequent to separation by ion chromatography has previously been developed. The method is based on Indirect Amperometric Detection whereby the decrease in the oxidation current, due to a dithiocarbamate ligand added post column, is monitored. Upon elution from the chromatographic column the metal ions are complexed by the ligand. As the complexes formed are electroinactive at the applied potential, the background current decreases according to the metal ion concentration. The method developed in this work involves addition to the reagent of Zn(II) as a auxiliary metal ion to displace the analyte metals from the chromatographic eluent ligand complexes after separation. Sodium bis(2-hydroxy-ethyl) dithiocarbamate was used as the postcolumn derivatising reagent. The addition of Zn(II) to the reagent causes some unforeseen behaviour in the chromatographic system.
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    Chromatographia 25 (1988), S. 199-204 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Column switching ; Catecholamines ; Urine ; Serum
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    Topics: Chemistry and Pharmacology
    Notes: Summary We developed an automated, two-column HPLC-method that can be used routinely to quantify the catecholamines norepinephrine and epinephrine in body fluids. The method is based on a new, laboratory-prepared SEC-HPAC column material, on the application of a microprocessor-controlled column-switching technique, and on the use of an integrated reaction system for postcolumn derivatization and trihydroxyindol-fluorescence monitoring. It allows the direct injection (upto 500 μl) of an appropriate biological fluid and distinguishes on its integrated sample-processing mode, its practicability, its chemoselectivity and-specivity, its detection limit (2 pg), its within- and between-run precision and its speed of analysis.
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  • 81
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Pheophytinatonicke(II) ; Chlorophyll ; Pheophytin
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    Topics: Chemistry and Pharmacology
    Notes: Summary HPLC determination of pheophytinatonicke(II) (Pheo-Ni) prepared by the replacement of magnesium(II) in chlorophyll with nicke(II) is described. The good separation of PheoNi was obtained by using chemically bonded C18 as the stationary phase and acetone-methanol (50∶50, vol/vol) as the mobile phase. Conventional spectrophotometric method was also used for the determination of PheoNi. For the synthetic samples prepared by mixing (pheophytinato a) nicke(II) [(Pheo-a) Ni] and (pheophytinato b) nicke(II) [(Pheo-b) Ni], analytical values obtained by the spectrophotometric method were very high compared to those obtained by HPLC. In the proposed HPLC method, (Pheo-a) Ni and (Pheo-b). Ni could be determined in the concentration range of 0.028–30μg/ml and 0.038–30μg/ml with relative standard deviations (n=10) of 3.1% and 0.8%, respectively.
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  • 82
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Flavonoid compounds ; Structure-retention relationships ; Reversed-phase systems
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    Topics: Chemistry and Pharmacology
    Notes: Summary Reversed-phase HPLC retention behaviour of different flavonoid compounds in different columns and with a range of methanol-buffer eluents was examined. Repeatibility and reproducibility of logk′ and Δlogk′ values were analyzed. Sharp group contributions, expressed as Δlogk′, were observed. These did not depend significantly on acid modifier type, column packing characteristics (C8 and C18) and dimensions (5,7 and 10μm) or the percentage of methanol in the mobile phase. A list of twelve group contributions is presented which is in agreement with literature data.
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  • 83
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    Chromatographia 25 (1988), S. 443-446 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Large scale separations ; Dissolution of silica ; Metallic contaminants
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    Topics: Chemistry and Pharmacology
    Notes: Summary Possible contamination of purified product by the silica matrix is of considerable importance when considering process scale high-performance liquid chromatography (HPLC) as a separation methodology. The stability of silica supports in normal phase, reversed phase and affinity chromatography modes has been examined with organic solvents and water. Both inorganic and organic components were found, contributed by the support, and the chromatographic and distillation equipment. In all cases, based on assumed values of production, they were found to contribute less than 0.01% of impurities. In critical cases crystallisation or dialysis may be considered as a last stage of purification, with re-chromatography to maximise yields.
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  • 84
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Fast atom bombardment mass spectrometry ; Nonionic detergents
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    Topics: Chemistry and Pharmacology
    Notes: Summary Microcolumn liquid chromatography (LC) combined with fast-atom-bombardment mass spectrometry (FABMS) was applied to the analysis of nonionic detergents. The porous silver filter attached to the top of the capillary fused-silica tubing worked as the interface for coupling of micro LC and FABMS.
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    Chromatographia 25 (1988), S. 577-581 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Process scale ; Examples of separations
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    Topics: Chemistry and Pharmacology
    Notes: Summary The flexibility of process scale high performance liquid chromatography is demonstrated by three examples of reversed-phase separations (a) a standard purification (b) isolation of trace compounds, and (c) recovery from crystallisation mother liquors. It was shown that a material, thought to be acceptably pure, contained a toxic impurity, and a remaining impurity, a previously unseen component of potential therapeutic interest. Favourable cost data were indicated for example (3).
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    Chromatographia 25 (1988), S. 717-720 
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Reversed-phase chromtography ; Antifungla agent ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A high-performance liqid chromatographic method is reported for the measurement of miconazole in systemic, fungal infectious patients. Pharmacokinetic data are presented for a single patient receiving miconazole therapy. Sample preparation involves protein precipitation by acetonitrile (1:1, vol/vol). Analyses are carried out on a reversed-phae chromatographic system using octadecylsilane stationary phase: a mobile phase consisting of 0.05 M acetate buffer (pH 7.4)acetonitrile (20:80, vol/vol) is used to elaute miconazole is quantified on the basis of ultraviolet absorption at 220 nm. The precision of the method ranged from 3.21% at 0.5 mg/L to 0.85% at 2.0 mg/L. The limit of quantification was established as 0.1 mg/L. Interference from other drugs that are co-adimistered such as amphotericin B, 5-fluorocytosine of ketoconazole and most other comonly encountered drugs was not observed.
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  • 87
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Fractional factorial experimental designs ; Ruggedness test ; Method validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Recently much attention has been directed to the validation of analytical methods. The level of validation will depend on the method application. If a method is developed for general use, for instance by different analysts, instruments or laboratories, then the effect of these changes need evaluation. This is normally referred to as ruggedness testing, where the limitations of the method to changes in the specified conditions are examined. This paper examines the use of Plackett-Burman fractional factorial experiment designs for ruggedness testing in high performance liquid chromatography (HPLC). The ability of these designs to identify confounding effects is applied to the stability indicating analysis of Salbutamol and its major degradation product, AH4045. The results show that confounding effects, proving extremely pertinent to HPLC, can be identified. The assay proved rugged to most tested changes although not to the use of column packing material from different manufacturers.
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  • 88
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Alkyl-bonded phases ; Retention behaviour ; Ligand density ; n-alkyl chain length
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    Topics: Chemistry and Pharmacology
    Notes: Summary Two series of bonded phases were synthesized employing LiChrospher Si 100, 10 μm and n-alkyldimethylmonochlorosilanes as silanizing reagents. In series A the n-alkyl chain length, n, of the bonded phase was varied between 1 and 20 at a constant ligand density of 3.5±0.2μmol·m−2. In series B the ligand density, d, was gradually changed from 0 to 4.1μmol·m−2 on the C1, C4, C6, C8 and C18 bonded phases, respectively. The capacity factors of benzoic acid esters and anilines as solutes were found to increase linearly with the n-alkyl chain length of packings at constant eluent composition (series A) up to a so-called critical chain length, ncrit, where the capacity factor remained constant. ncrit was in the range from 11 to 14. The same pattern was observed when plotting the solute capacity factor against the ligand density of the packing at constant n and constant eluent composition (series B). The critical ligand density, αcrit, varied between 2.3 and 3.2 μmol·m−2 depending on n and the solute. Furthermore, solute retention was slightly higher on RP packings with an even number of carbon atoms in the alkyl chain than on those with an odd number. These findings are consistent with the results of Berendsen and de Galan (J. Chromatogr., 196, 21 (1980)), Dill (J. Phys. Chem., 91, 1980 (1987)) and Simpson and Lau (to be published). The observed phenomena reflect the dynamic structure of RP silicas which are related to the mobility of solvated n-alkyl chains. Due to the lack of a precise conformational analysis of the surface of RP silicas, a semiquantitative model was applied to interprete the described dependencies.
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  • 89
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    Bulletin of experimental biology and medicine 106 (1988), S. 1699-1702 
    ISSN: 1573-8221
    Keywords: platelets ; aggregation ; refractoriness ; calcium ; ADP
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    Topics: Biology , Medicine
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  • 90
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    Bulletin of experimental biology and medicine 105 (1988), S. 181-183 
    ISSN: 1573-8221
    Keywords: diabetes mellitus ; calcium ; anticalcitonin antibodies ; reaction of enzyme-labeled antibodies
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  • 91
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    Bulletin of experimental biology and medicine 105 (1988), S. 244-247 
    ISSN: 1573-8221
    Keywords: biorhythms ; calcium ; immunization ; helio-geophysical rhythms
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  • 92
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    Journal of pharmacokinetics and pharmacodynamics 16 (1988), S. 573-593 
    ISSN: 1573-8744
    Keywords: bioavailability ; drug ; metabolite ; first-pass hepatic loss ; pharmacologic response ; estimation ; bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Many drugs with low oral bioavailability due to substantial first-pass hepatic loss form pharmacologically active metabolites. In such cases, the pharmacologic activity after oral administration is greater than anticipated from bioavailability data, based on chemical assay of drug alone. This paper explores the use and meaning of pharmacologic data to assess bioavailability under these circumstances. Two steady-state concepts are introduced: a metabolite-to-drug intravenous delivery rate potency ratioand an effective bioavailability,defined as the ratio of intravenous-to-oral delivery rates of drug required to produce the same response. Using a combined phar-macokinetic-pharmacodynamic model, the impact of various factors on the effective bioavailability and on its estimation, using the intravenous-to-oral dose ratio required to produce the same area under the response time curve after acute administration, are explored. It is proposed that attention be centered more on comparison of rates of administration, or doses, that produce equal responses than on bioavailability per se.
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  • 93
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    Pharmacy world & science 10 (1988), S. 93-95 
    ISSN: 1573-739X
    Keywords: Anthracyclines ; Chemistry ; Drug stability ; Mitomycins
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  • 94
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    Pharmacy world & science 10 (1988), S. 101-116 
    ISSN: 1573-739X
    Keywords: Chemistry ; Chromatography ; Etoposide ; Immunoassay ; Metabolism ; Podophyllotoxin ; Pharmacokinetics ; Teniposide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Etoposide (VP 16-213) and teniposide (VM 26) are semisynthetic epipodophyllotoxin derivatives active against a variety of tumours. The clinical efficacy has led to an increasing interest in these compounds. This review presents information on the mechanism of action, biochemical pharmacology, bioanalysis, metabolism and pharmacokinetics of etoposide and teniposide.
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  • 95
    ISSN: 1573-8744
    Keywords: Michaelis-Menten kinetics ; sinusoidal perfusion model ; venous equilibration model ; distributed model ; convection-dispersion model ; organ heterogeneity ; bioavailability ; pooling of data ; kinetic parameter estimation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract What can be inferred from limited clinical data by using current models of hepatic elimination? We examined this question by analyzing previously published data on the steady-state uptake of the anticancer agent 5-fluorouracil (5-FU) in seven cancer patients in terms of the venous equilibration model, the undistributed and distributed forms of the sinusoidal perfusion model, and the convection-dispersion model. Because of appreciable extrasplanchnic removal of 5-FU, the value of the steady infusion rate was not used in our analysis. When the data from all patients were pooled by plotting the measured hepatic venous concentration against the measured hepatic arterial concentration, the high concentration data fell on a limiting straight line of slope 1, indicating that at high dose rates elimination of 5-FU in both the liver and gastrointestinal tract was close to saturation. The intercept of this line gave a model-independent estimate of Vmax/Q= 48.0±11.6 (SD) μM for the pooled data set, where Vmax is the maximum splanchnic elimination rate of 5-FU, and Q is the hepatic blood flow. The low concentration data points fell on a limiting straight line through the origin, from which model-dependent values of the Michaelis constant were determined. The venous equilibration model gave K m=9.4μM,while the undistributed sinusoidal perfusion model gave K m * =26,5μM. With these values of K m,both models fit the pooled data equally well. These methods were applied to analyses of the five individual data sets which contained sufficiently high concentration data points. The resulting mean values were Vmax/Q=41.0±5.1 (sem) μM,K m=8.4±1.3μM and K m * =23.2±3.2 μM. However, the splanchnic region is a highly heterogeneous organ system, for which an undistributed analysis provides no more than an upper bound on the Michaelis constant K m + (K m + ⩽K m * ).A perfusion model distributed to represent total splanchnic elimination is developed in the Appendix. Using previous estimates of the degree of functional heterogeneity in the liver alone, this model yields K m + values for individual patients which have a mean of 20.3±2.8 μM.
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  • 96
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    Cellular and molecular neurobiology 8 (1988), S. 115-128 
    ISSN: 1573-6830
    Keywords: adrenal gland ; chromaffin cells ; phorbol ester ; digitonin ; secretion ; calcium ; trypsin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. Catecholamine secretion from digitonin-treated chromaffin cells is stimulated directly by micromolar Ca2+ in the medium. The permeabilized cells are leaky to proteins. 2. In this study trypsin (30–50µg/ml) added to cells after digitonin treatment completely inhibited subsequent Ca2+-dependent catecholamine secretion. The same concentrations of trypsin did not inhibit secretion from permeabilized cells if trypsin was present only prior to cell permeabilization. 3. The data indicate that trypsin entered digitonin-treated chromaffin cells which were capable of undergoing secretion and that an intracellular, trypsinsensitive protein is involved in secretion. Chymotrypsin was less potent but had effects similar to those of trypsin. 4. The enhancement of Ca2+-dependent secretion from permeabilized chromaffin cells induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by trypsin added simultaneously with Ca2+ to permeabilized cells at concentrations (3–10µg/ml) which had little or no effect on Ca2+-dependent secretion from cells untreated with TPA. Ca2+-dependent secretion in TPA-treated cells was reduced by trypsin only to the level that would have occurred in cells not treated with TPA. Trypsin reduced the large TPA-induced increment of membrane-bound protein kinase C. 5. The data indicate that Ca2+-dependent secretion in the absence of TPA does not require aTPA-like effect of Ca2+ to activate protein kinase C. Protein kinase C activation by TPA probably enhances Ca2+-dependent secretion by modulating the normal Ca2+-dependent pathway or by activating another Ca2+-dependent pathway which functions in parallel to the normal pathway.
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  • 97
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    Cellular and molecular neurobiology 8 (1988), S. 129-138 
    ISSN: 1573-6830
    Keywords: GTP-binding proteins ; calcium ; exocytosis ; guanine nucleotides ; adrenocorticotropic hormone (ACTH) ; AtT-20 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. We have examined the effects of guanine nucleotides on ACTH secretion from digitonin-permeabilized AtT-20 cells, with the aim of analyzing the involvement of GTP-binding proteins (G proteins) in the secretory process. 2. AtT-20 cells permeabilized with 20µM digitonin displayed calciumdependent secretion. The EC50 of calcium was ~2µM and the maximal stimulation was 350% of basal release. 3. Nonhydrolyzable guanine nucleotides also stimulated ACTH release, in a virtually Ca2+-free medium. The EC50 of guanosine 5′-(3-O-thio)triphosphate (GTP γ S) was ~15µM and the maximal stimulation was ~230% of basal release. The effects of calcium and guanine nucleotides were not additive. 4. In the presence of the inhibitory hormone, somatostatin guanine nucleotides inhibited the calcium-stimulated secretion. 5. Both the stimulatory and the inhibitory effects on secretion of guanine nucleotides were independent of changes in cyclic AMP (cAMP) and calcium. It is suggested that G proteins influence an unknown step in the secretion process, which would be near or at the exocytotic site. 6. The results can be explained by assuming the existence of two types of G proteins, one with stimulatory effects on exocytotic release (GeS) and another with inhibitory effects (GeI).
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  • 98
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    Pharmaceutical research 5 (1988), S. 44-47 
    ISSN: 1573-904X
    Keywords: estradiol ; prodrugs ; bioavailability ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Prodrugs of β-estradiol (1) were prepared with the objective of improving its oral bioavailability. β-Estradiol-3-acetylsalicylate (2), β-estradiol-3-salicylate (3), and β-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.
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  • 99
    ISSN: 1573-5117
    Keywords: deepwater rice ; water chemistry ; diel change ; oxygen ; anoxic ; calcium ; Eichhornia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The chemistry of water in fields at two Bangladesh deepwater rice locations is compared. Although Manikganj lies in the Jamuna (-Brahmaputra) floodplain and Sonargaon in the old Meghna floodplain, their chemistries during the flood season are similar, apart from higher Mg % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGadiiEayaara% aaaa!3703!\[\bar x\]: 3.57 v.1.8 mg 1−1), Ca (% MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGadiiEayaara% aaaa!3703!\[\bar x\]: 13.1 v.4.5 mg l−1 ), pH and total alkalinity at the former. Diel changes in oxygen and sometimes also pH were evident 10 cm below the surface in deepwater rice fields, but such changes were typically much greater in fallow fields. Measurements made between 1400 and 1600 h in a range of habitats showed a trend for high pH values to be associated with high O2 values. Water in Eichhornia beds had the lowest values, deepwater rice fields were intermediate and fallow fields and other open areas typically had the highest values. O2 concentrations in excess of 15 mg l−1 and pH values of about 10.0 sometimes occurred in fallow fields with dense masses of submerged plants and loosely associated algal flocs. There was an increasing tendency for the water to become anoxic towards the end of the season and water 10 cm above the bottom was almost or entirely anoxic in deepwater rice fields at both locations over the whole 24-h period of 4/5 October, at a time when the depth of the water was starting to drop. Nitrite increased and sulphate decreased at both locations towards the end of the season.
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  • 100
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    Hydrobiologia 160 (1988), S. 9-18 
    ISSN: 1573-5117
    Keywords: bioassay ; phosphorus ; sediments ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Eroding bank soils and riverine suspended sediments from the Flathead River-Lake ecosystem, Montana, USA, were cultured with the alga Selenastrum capricornutum Printz in PAAP medium with the sediments as the sole source of phosphorus. Extraction of phosphorus by NaOH and nitrilotriacetic acid (NTA) solutions were compared to results from algal bioassays. The fine sediment particles transported into Flathead Lake during spring runoff had the highest availability (i.e. 6% of total phosphorus). Bank soils which contained the greatest percentage of fine clays exhibited similar (i.e. 4% of total phosphorus) availability. Bank soils containing predominantly organic phosphorus had the lowest availability. Spearman's rank correlation indicated significance at the 5% test level between algal assay estimates of available phosphorus and both chemical extraction techniques.
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