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  • 1
    Electronic Resource
    Electronic Resource
    Vitamin E content of different animal products: Influence of animal nutrition (1997)
    Springer
    European journal of nutrition 36 (1997), S. 23-27 
    Details
    ISSN: 1436-6215
    Keywords: Vitamin E ; Fleisch ; Fettgewebe ; Leber ; Eigelb ; Vitamin E ; meat ; adipose tissue ; liver ; egg yolk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The α-tocopherol content of different meat cuts was examined. Chicken thigh had the highest vitamin E content, followed by chicken breast and pork shoulder (p〈0.05). The lowest concentrations were found in longissimus dorsi muscle from pork, beef, veal and in beef shoulder. Considering the average daily lean meat consumption (105 g) in Switzerland, recommendation for daily vitamin E intake was met to 3 %. Supplementation of 200 mg α-tocopherol acetate/kg feed to pigs and laying hens significantly increased the α-tocopherol content in all examined products. The α-tocopherol accumulation differed according to the following ranking: egg yolk 〉 liver 〉 adipose tissue 〉 musculus longissimus dorsi. The α-tocopherol:energy ratios were 28.8, 7.3, 0.9 and 1.2 mg/MJ for egg yolk, liver, adipose tissue and longissimus dorsi muscle of the vitamin E supplemented groups, respectively. The results showed that meat, with the exception of chicken thigh, is not an important supplier of vitamin E, not even from animals fed a vitamin E enriched diet. Egg yolk became a good source of vitamin E for human nutrition by dietary modification.
    Notes: Zusammenfassung In der vorliegenden Studie wurde der α-Tocopherolgehalt verschiedener Fleischstücke untersucht. Hähnchenschenkel hatte den höchsten α-Tocopherolgehalt, gefolgt von Hähnchenbrust und Schweineschulter (p〈0.05). Die niedrigsten Konzentrationen wurden im Musculus longissimus dorsi vom Schwein, Rind, Kalb und in der Rindsschulter nachgewiesen. Mit dem durchschnittlichen, täglichen Verzehr an magerem Fleisch (105 g) in der Schweiz wurden die Empfehlungen für die tägliche Vitamin E-Zufuhr zu 3 % gedeckt. Die Supplementierung des Schweine- und Legehennenfutters mit 200 mg α-Tocopherolacetat/kg führte zu einem signifikanten Anstieg des α-Tocopherolgehaltes in allen untersuchten Produkten. Die α-Tocopherolakkumulierung unterschied sich gemäß folgender Rangordnung: Eigelb 〉 Leber 〉 Fettgewebe 〉Musculus longissimus dorsi. Die Nährstoffdichten betrugen 28.8, 7.3, 0.9 und 1.2 mg α-Tocopherol/MJ für Eigelb, Leber, Fettgewebe und Musculus longissimus dorsi der jeweiligen mit Vitamin E supplementierten Gruppe. Diese Ergebnisse zeigen, daß Fleisch, mit Ausnahme des Hähnchenschenkels, von Tieren mit supplementierten Diäten kein bedeutender Vitamin E-Lieferant ist. Hingegen wurde Eigelb durch fütterungsbedingte Modifikation zu einer guten Vitamin E-Quelle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01618896
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  • 2
    Electronic Resource
    Electronic Resource
    Analysis of magnetic material in the human heart, spleen and liver (1997)
    Springer
    BioMetals 10 (1997), S. 351-355 
    Details
    ISSN: 1572-8773
    Keywords: heart ; liver ; maghemite ; magnetite ; spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Isothermal remanent magnetization (IRM) acquisition and alternating field (A.F.) demagnetization analyses were performed on human heart, spleen and liver samples resected from cadavers. The magnetic properties of the samples were measured both at 77K and at 273K. A.F. demagnetization was performed at 273K. Results from the analyses of the tissue indicate the presence of ferromagnetic, fine-grained, magnetically interacting particles which, due primarily to magnetic properties, are thought to be magnetite and/or maghemite. The presence of superparamagnetic particles can be inferred from the increase in saturation IRM values when measured at 77K compared with measurements at 273K and the decay of remanent magnetization upon warming from 77K. The concentration of magnetic material (assuming it is magnetite or maghemite) in the samples varies from 13.7 ng g-1 to 343 ng g-1, with the heart tissue generally having the highest concentration. The presence of magnetic material in these organs may have implications for the function of biogenic magnetite in the human body.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018340920329
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  • 3
    Electronic Resource
    Electronic Resource
    X-ray fluorescence in the assessment of inter-elemental interactions in rat liver following lead treatment (1995)
    Springer
    BioMetals 8 (1995), S. 105-110 
    Details
    ISSN: 1572-8773
    Keywords: energy dispersive X-ray fluorescence ; liver ; lead toxicity ; inter-elemental effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Energy dispersive X-ray fluorescence technique was employed to study the interactions of lead (50 and 100 mg/kg body wt) with K, Fe, Cu, Zn, Br and Rb in rat liver. Lead was administered orally to rats daily for dosage periods of 1 and 4 months (short and long terms). Hepatic Fe levels were found to increase significantly with the supplementation of low and high doses of lead for both the treatment periods, although the increase was more pronounced following long-term treatment. The levels of hepatic K, Cu and Br were seen to decrease significantly over both time intervals. Moreover, hepatic Rb contents were lowered with the short-term supplementation of low doses of lead. In contrast, Rb and Zn levels were increased when lead was administered for the longer period at both dose levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00142008
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  • 4
    Electronic Resource
    Electronic Resource
    Occurrence of polyploidy and multinuclearity in the differentiating liver of chick embryo (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 986-988 
    Details
    ISSN: 1420-9071
    Keywords: Chick embryos ; liver ; chick ; chick ; liver ; nuclear size ; polyploidy ; multinuclearity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Increase in nuclear size in liver has been used as an index of polyploidy. It has long been considered that the occurrence of polyploidy and multinuclearity are characteristics of mammalian liver. The present study shows the occurrence of these phenomena in the liver of birds, so these features are not confined to mammals. 3 classes of nuclear size groups have been identified. The simultaneous occurrence of polyploidy and binuclearity indicates some sort of interrelationship between them.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946472
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  • 5
    Electronic Resource
    Electronic Resource
    The effect of graded ascorbic acid intake on the activity of GSH-Px in the liver of female guinea pigs (1995)
    Springer
    European journal of nutrition 34 (1995), S. 220-223 
    Details
    ISSN: 1436-6215
    Keywords: Ascorbic acid ; glutathioneperoxidase ; lipid peroxides ; liver ; Ascorbinsäure ; Glutathion-Peroxidase ; Lipidperoxiden ; Leber
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Verschiedene Werte an antioxidativem Potential, erzeugt mit Hilfe verschiedener Konzentrationsstufen an Ascorbinsäure (1, 10, 100 mg/Tier/Tag) führten zu Veränderungen in der GSH-Px Aktivität und der Menge den Lipidperoxiden in der Leber von Meerschweinchen. Die Gruppe mit der kleinsten Dosierung (1 mg) von Ascorbinsäure hatte die niedrigste GSH-Px Aktivität und den höchsten Anteil an Lipidperoxiden. Die zwei anderen Gruppen zeigten eine Erhöhung der GSH-Px Aktivität und Senkung von Lipidperoxiden auf. Es bestand kein Unterschied zwischen den Gruppen mit der Dosis von 10 und 100 mg Ascorbinsäure.
    Notes: Summary Differing antioxidant potentials created by graded ascorbic acid supplementation (1, 10, 100 mg per animal daily) evoked changes in the level of glutathione peroxidase activity and lipid peroxides in the liver of female guinea pigs. The group with the lowest ascorbic acid intake (1 mg) had the lowest activity of glutathione peroxidase and the highest level of lipid peroxides. The two other groups (10 and 100 mg) showed enhancement of glutathione peroxidase activity and decline in lipid peroxides. There was no difference between the groups with 10 and 100 mg ascorbic acid intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623161
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  • 6
    Electronic Resource
    Electronic Resource
    Untersuchungen zum Einfluß einer unterschiedlichen Riboflavinversorgung während der Laktation auf den Riboflavingehalt von Milch, Leber und Restkörper laktierender Ratten (1997)
    Springer
    European journal of nutrition 36 (1997), S. 176-181 
    Details
    ISSN: 1436-6215
    Keywords: Riboflavin ; Milch ; Leber ; Restkörper ; Laktation ; Ratte ; Riboflavin ; milk ; liver ; carcass ; lactation ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The present study investigated the effect of various dietary riboflavin supplementations (0 to 4 000 mg/kg) during lactation on riboflavin concentrations of liver, carcass (bled body without intestine and liver), and milk in the rat. The experiment was conducted until the 14th day of lactation; milk samples were drawn on the 7th and 13th day of lactation. Riboflavin concentrations of milk raised continuously with increasing riboflavin supplementation; in the range between 0 and 10 mg/kg riboflavin supplementation, there was a linear relationship, and in the range between 12 and 4 000 mg/kg there was a logarithmic relationship between riboflavin supplementation and riboflavin concentration in the milk. Maximum riboflavin concentration of milk obtained by supplementation with 4 000 mg/kg was twelve-fold higher than without riboflavin supplementation. For riboflavin supplementation up to 12 mg/kg, riboflavin concentrations in milk on the 7th day of lactation and that on the 13th day of lactation were not different. In contrast, in rats fed diets with higher riboflavin supplementation, riboflavin concentrations were higher by 25 % in average in milk on the 13th day of lactation than in milk on the 7th day of lactation. Contrary to the milk, riboflavin concentrations in liver and carcass exhibited a saturation, which was achieved at a supplementation of 6 mg/kg (liver) and 10 mg/kg (carcass), respectively. Maximum riboflavin concentrations obtained at a supplementation of 4 000 mg/kg were 1.9- and 2.3-fold higher for liver and carcass, respectively, than concentrations obtained without riboflavin supplementation. The dose-response relationship using riboflavin concentrations of liver and carcass as response factors indicates a riboflavin requirement of 8 to 9 mg/kg for lactating rats fed a semisynthetic diet with 17.4 MJ ME/kg dry matter and 20.8 % protein in dry matter.
    Notes: Zusammenfassung In der vorliegenden Arbeit wurde der Einfluß unterschiedlicher Riboflavinzulagen zum Futter (0 bis 4 000 mg/kg) während der Laktation auf die Riboflavinkonzentrationen in Leber, Restkörper (ausgebluteter Gesamtkörper ohne Magen-Darm-Trakt und Leber) und Milch von Ratten untersucht. Der Versuch dauerte bis zum 14. Laktationstag; Milchproben wurden am 7. und am 13. Laktationstag gewonnen. Die Riboflavinkonzentration der Milch erhöhte sich mit steigender Zulage stetig, wobei im Bereich zwischen 0 und 10 mg Riboflavinzulage/kg Futter eine lineare und im Bereich zwischen 12 und 4 000 mg/kg eine logarithmische Funktion vorlag. Die maximale Riboflavinkonzentration in der Milch bei einer Zulage von 4 000 mg/kg war dabei etwa zwölfmal so hoch wie bei fehlender Zulage. Bei Riboflavinzulagen bis 12 mg/kg unterschieden sich die Riboflavinkonzentrationen der Milch am 7. und 13. Laktationstag nicht. Bei den höheren Zulagen waren die Konzentrationen der Milch am 13. Laktationstag im Mittel um 25 % höher als am 7. Laktationstag. Im Gegensatz zur Milch zeigte sich in Leber und Restkörper eine Sättigung der Riboflavinkonzentrationen, die bei einer Riboflavinzulage von 6 mg/kg (Leber) bzw. 10 mg/kg (Restkörper) erreicht war. Die maximalen Riboflavinkonzentrationen bei Zulagen von 4 000 mg/kg waren dabei 1,9 (Leber) bzw. 2,3 (Restkörper) mal so hoch wie bei fehlender Riboflavinzulage. Diese Befunde sprechen für eine ausgeprägte homöostatische Kontrolle der Riboflavinkonzentrationen im Organismus. Anhand von Dosis-Wirkungsbeziehungen mit den Riboflavinkonzentrationen in Leber und Restkörper als Wirkungskriterien leitete sich bei Verwendung des halbsynthetischen Futters (17,4 MJ ME/kg Trockenmasse (T), 20,8 % Rohprotein in T) ein Riboflavinbedarf von 8 bis 9 mg/kg Futter für die laktierende Ratte ab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01611397
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  • 7
    Electronic Resource
    Electronic Resource
    Influence of environmental temperature on in vivo energy expenditure and in vitro ouabain-sensitive respiration in duodenal mucosa and liver in rats fed different levels of dietary fibre or protein (1997)
    Springer
    European journal of nutrition 36 (1997), S. 278-284 
    Details
    ISSN: 1436-6215
    Keywords: Environmental temperature ; energy expenditure ; ouabain-sensitive respiration ; duodenal mucosa ; liver ; rats ; Umgebungstemperatur ; Energieumsatz ; Quabain-sensitive Respiration ; Duodenalmukosa ; Leber ; Ratten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Die Wirkung der Umgebungstemperatur (18°C oder 28°C) und des Fasergehalts in der Diät (g je kg Trockensubstanz (TS) niedrig - 68, mittel - 110, hoch - 157) oder des Proteingehalts (g je kg TS niedrig - 91, mittel- 171, hoch - 262) auf den Verdauungstrakt, die Darmmasse, den Energieumsatz und auf die mit der Na+, K+-ATPase-Aktivität zusammenhängenden Respiration von Duodenalmukosa und Leber wurde bei 72 Wistar-Ratten in wiederholten Experimenten untersucht. Der Gesamte und Quabain-sensitive (ein Maß der Na+, K+-ATPase Aktivität) O2-Verbrauch der Gewebe wurde in vitro polarographisch ermittelt (YSI-biologische Sauerstoff-Erfassung nach dem Clark-Meßprinzip). Die Wärmeproduktion (WP) intakter Tiere wurde über Respirationskammern mit offenem Gasaustausch erfaßt. Die bei 18°C gehaltenen Ratten wiesen im Vergleich zu 28°C eine höhere Darmmasse auf. Die Masse an leerem Dünndarm, Caecum und Colon stieg mit ansteigendem Fasergehalt in der Diät (P〈0.05). Die WP als Korrelat der umsetzbaren Energie war nur im 1. Experiment höher (P〈0.05) bei 18°C als bei 28°C. Bei niedriger Proteinstufe war die WP signifikant höher (P 0.05) als bei den anderen Stufen. Verglichen mit 28°C erzeugte 18°C einen ansteigenden Gesamt- und Quabain-sensitiven O2-Verbrauch in der Duodenalmukosa. Die Leber reagierte nicht auf Temperaturunterschiede. Jedoch war ihr Quabain-sensitiver O2-Verbrauch bei niedrigem Proteingehalt in der Nahrung höher (P〈0.05) als bei den anderen Varianten. Bei niedrigem Fasergehalt war der gesamte und Quabain-sensitive O2-Verbrauch der Duodenalmukosa höher als bei den anderen Fasergehaltsvarianten. Die In-vitro-Ergebnisse stimmten mit der WP und dem O2-Verbrauch intakter Tiere überein.
    Notes: Summary Seventy two Wistar rats were used in two repeat studies to investigate the effect of environmental temperature (18°C or 28°C) and increasing levels of dietary fibre (low, 68 g/kg DM; medium 110 g/kg DM; high, 157 g/kg DM) or protein (low, 91 g/kg DM; medium, 171 g/kg DM; high, 262 g/kg DM) on digestive tract, visceral organ size, energy metabolism, and respiration attributable to Na+,K+-ATPase activity in duodenal mucosa and liver. Total and ouabain-sensitive (a measure of Na+,K+-ATPase activity) O2 consumptionin vitro of tissues were measured polarographically using a Clark-style YSI biological O2 monitor. Whole body heat production (in vivo) was measured using open-circuit respiration chambers. The weight of the visceral organs was higher in rats housed at 18°C than at 28°C. The empty weight of the small intestine, caecum, and colon increased as the level of dietary fibre increased (P 0.05). Heat production as a proportion of metabolizable energy was higher (P〈0.05) at 18°C than at 28°C in the first experiment but this difference was not significant in the second experiment. Rats fed the low protein diet had significantly higher (P〉0.05) heat production than those fed medium or high protein diets. Compared to 28°C, environmental temperature of 18°C caused an increased total and ouabain-sensitive O2 consumption in duodenal mucosa. There was no significant effect of environmental temperature on total and ouabain-sensitive O2 consumption in the liver. However, ouabain-sensitive O2 consumption in liver was significantly higher (P 0.05) when rats were fed a low protein diet compared to the medium or high protein diet. Total and ouabain-sensitive O2 consumption increased in duodenal mucosa of rats fed low level of dietary fibre compared to the medium or high dietary fibre diets. Thein vitro results corresponded with the whole animal energy expenditure and O2 consumptionin vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01617798
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  • 8
    Electronic Resource
    Electronic Resource
    Oyster mushroom (Pleurotus ostreatus) reduces the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat liver microsomes (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 589-591 
    Details
    ISSN: 1420-9071
    Keywords: Oyster mushroom (Pleurotus ostreatus) ; cholesterol ; serum ; lipoproteins ; liver ; HMG-CoA reductase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of dried oyster mushroom (Pleurotus ostreatus) on cholesterol (C) content in serum, in lipoproteins and in liver, and on the activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in liver microsomes, was studied in male rats (strain Wistar, initial body weight 75 g) fed on low-cholesterol (9 mg/100 g) and high-cholesterol (0.3%) diets. Addition of 5% oyster mushroom to both diets reduced significantly the C-content in serum (by 30%), in very-low- and low-density lipoproteins (in a 1∶1 ratio to the decrease of total serum C) and in liver (by 50%), as well as the activity of HMG-CoA reductase (by more than 30%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02128749
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  • 9
    Electronic Resource
    Electronic Resource
    Plasma adenosine concentrations are elevated in Dahl salt-sensitive rats (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 227-229 
    Details
    ISSN: 1420-9071
    Keywords: Adenosine ; Dahl salt-sensitive rats ; high-performance liquid chromatography ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We measured plasma levels of adenosine in Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) to examine the potential role of adenosine in cardiovascular regulation in this type of hypertension. Plasma adenosine concentrations were significantly higher in DS than in DR. The NaCl content in the diet did not affect plasma adenosine concentration in either DS or DR. Significant positive correlation was found between adenosine concentrations and systolic blood pressure when the data for DS and DR were analyzed together. These results suggest that adenosine may play an important role in the pathophysiology of hypertension in DS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01931102
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  • 10
    Electronic Resource
    Electronic Resource
    Reserpine and breast cancer in women in Germany (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 79-83 
    Details
    ISSN: 1432-1041
    Keywords: Reserpine ; cancer ; mammary gland ; women ; benign breast disease ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562896
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  • 11
    Electronic Resource
    Electronic Resource
    Monoamine metabolites in cerebrospinal fluid during treatment with clonidine or alprenolol (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 125-128 
    Details
    ISSN: 1432-1041
    Keywords: Clonidine ; alprenolol ; amine metabolites ; cerebrospinal fluid ; hypertension ; noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Lumbar cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline (4-hydroxy-3-methoxyphenyl glycol, HMPG), serotonin (5-hydroxyindoleacetic acid) and dopamine (homovanillic acid) were measured before and during the administration of clonidine or alprenolol to hypertensive patients. The noradrenaline receptor stimulant clonidine significantly decreased the CSF level of HMPG, but there was no consistent change in the concentration of serotonin or dopamine metabolites. Patients on alprenolol showed no change in the levels of these metabolites in CSF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562903
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  • 12
    Electronic Resource
    Electronic Resource
    Plasma concentrations of propranolol in patients with essential hypertension (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 155-157 
    Details
    ISSN: 1432-1041
    Keywords: Propranolol ; plasma concentration ; hypertension ; individual drug dosage ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with essential hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606403
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  • 13
    Electronic Resource
    Electronic Resource
    Long term effect of timolol and hydrochlorothiazide, or hydrochlorothiazide and amiloride, in essential hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: beta adrenergic blockers ; diuretics ; hypertension ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645129
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  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of tolamolol in the treatment of hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 171-174 
    Details
    ISSN: 1432-1041
    Keywords: Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609855
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  • 15
    Electronic Resource
    Electronic Resource
    A comparison of slow release oxprenolol with conventional oxprenolol in the treatment of hypertension (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 77-81 
    Details
    ISSN: 1432-1041
    Keywords: Oxprenolol ; slow release oxprenolol ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The antihypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend.
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    URL: http://dx.doi.org/10.1007/BF00607434
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  • 16
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    Transplacental passage of atenolol in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 93-94 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; transplacental passage ; pregnancy ; hypertension ; maternal-fetal ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in six cases, showing that there is transplacental passage of the drug. In the seventh case, who had stopped taking atenolol more than one day before delivery, neither maternal nor umbilical serum contained a measurable quantity of the drug. Atenolol concentration varied 3- to 6-fold between individuals, but there was no systematic difference between maternal and umbilical levels. It seems reasonable to assume that during steady state conditions the blood level of atenolol in mother and fetus is approximately equal, and that fetal accumulation of the drug does not occur.
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    URL: http://dx.doi.org/10.1007/BF00607437
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  • 17
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    Withdrawal of guanfacine after long-term treatment in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 19-24 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
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    URL: http://dx.doi.org/10.1007/BF00558376
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  • 18
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    Electronic Resource
    Prescription of hypotensives in general practice (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 309-317 
    Details
    ISSN: 1432-1041
    Keywords: General practitioners ; hypertension ; diagnosis/therapy/control ; prescription pattern ; hypotensive drugs ; drugsale statistics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Based upon regional drug sales statistics, two Norwegian counties with a consumption of hypotensives below and two above average were selected for a prescription study among general practitioners (GPs). The first part of the study involved collection of all the GPs' prescriptions for antihypertensive treatment during the month of October 1975. Immediately afterwards the GPs filled in a questionnaire in which they described their diagnostic and therapeutic criteria and procedures for arterial hypertension. Both parts of the study were analysed and compared. Of the GPs approached 154 (54%) participated. A total of 4095 prescriptions for 3253 patients were collected, 65% of whom were females and 35% were males. GPs alone treated 72% of the patients, and of the others 11% had been referred to specialists, 8% had been admitted to hospital, and 5% had had both procedures. The decision of whether or not to start drug treatment was based upon absolute systolic and diastolic BP levels as related to age, but various other patient factors, such as complicating diseases, family history of cardiovascular disease and cooperation/motivation for treatment, were also considered. The average control interval was 4.4 months (range 1 to more than 6 months) and it increased with the age of the patients. About half of the GPs started drug treatment in young patients with beta-blockers, whereas diuretics were preferred for older subjects. Of the total number of prescriptions, diuretics accounted for 50%, synthetic hypotensives (α-methyldopa, hydralazine, guanethidine etc.) for 33%, and beta-blockers for 17%. The therapeutic efficacy, in terms of BP reduction upon drug treatment, was evaluated in relation to age, both in those patients treated solely by GPs and in those referred to a specialist. Patient compliance and adverse drug reactions were also registered, although with considerable variation between the individual participating GPs. During postproject discussions, the GP-participants stated that this type of project was a valuable model for post-graduate training through testing of individual criteria for diagnostic and therapeutic procedures.
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    URL: http://dx.doi.org/10.1007/BF00611899
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  • 19
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    Double-blind trial comparing guanfacine and methyldopa in patients with essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 309-315 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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    URL: http://dx.doi.org/10.1007/BF00544579
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  • 20
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    Haemodynamic profile of captopril treatment in various forms of hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 163-168 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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    URL: http://dx.doi.org/10.1007/BF00544593
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  • 21
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    Acute effects of a new vasodilator, Ro 12-4713, on blood pressure, plasma renin activity, aldosterone and catecholamine levels, and renal function in hypertensive and normal subjects (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 169-177 
    Details
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m2. Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=−0.60; P〈0.02), and positively with those in plasma norepinephrine (r=0.55; P〈0.05) and renin (r=0.62, P〈0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=−0.65; P〈0.01), and positively with those in plasma norepinephrine (r=0.58; P〈0.05). 24 h-urinary sodium excretion was significantly (P〈0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P〈0.05) and inversely with supine plasma renin activity (r=−0.63; P〈0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m2; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P〈0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P〈0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.
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    URL: http://dx.doi.org/10.1007/BF00544594
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  • 22
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    Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 309-313 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; therapeutic window ; steady state concentration ; pharmacokinetics ; cardiovascular effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 µg/kg to patients with essential hypertension (n=6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time — plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the antihypertensive effect was established. At a plasma clonidine concentration of 0.65±0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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    URL: http://dx.doi.org/10.1007/BF00548760
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  • 23
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    Effect of oxprenolol and metoprolol on serum lipid concentration (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; oxprenolol ; hypertension ; beta-blockers ; HDL-cholesterol ; intrinsic sympathomimetic activity ; cardioselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p〈0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.
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  • 24
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    Pafenolol, a new β1-selective blocking agent, in mild hypertension. Result of an inpatient study and a subsequent outpatient follow-up (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: pafenolol ; hypertension ; antihypertensive therapy ; beta1-blocking agent ; exercise tests ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pafenolol, a new selective adrenergic beta1-blocking agent, has been tested for the first time in 6 hypertensive patients. After single oral doses of pafenolol 25 to 100 mg, there was a marked reduction in heart rate and systolic blood pressure during exercise tests. These effects were dose dependent. A significant positive correlation was found between the reduction in heart rate during exercise and the plasma level of pafenolol 5 hours after drug intake (correlation coefficient r=0.94). Side effects were mild and seemed to be dose dependent. It is concluded that this new beta1-blocking agent was effective in reducing blood pressure and was well tolerated.
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    URL: http://dx.doi.org/10.1007/BF00543483
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  • 25
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    Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 687-693 
    Details
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
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    URL: http://dx.doi.org/10.1007/BF00541926
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  • 26
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    Once daily indapamide in the treatment of the elderly and young hypertensive (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 397-405 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; cardiovascular reflexes ; diuretic effect ; blood pressure variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.
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    URL: http://dx.doi.org/10.1007/BF00549585
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  • 27
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    Dose-titrated, double-blind, cross-over comparison of a selective beta-blocker and methyldopa in the treatment of hypertension (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 159-162 
    Details
    ISSN: 1432-1041
    Keywords: Tolamolol ; methyldopa ; comparative trial ; hypertension ; beta-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy and toxicity of tolamolol and methyldopa in hypertensive patients has been compared by a dose-titrated, double-blind, cross-over study. Thirteen patients completed the trial. Within the dose ranges investigated (tolamolol — 300 mg/day — 900 mg/day; methyldopa — 750 mg/day — 2250 mg/day) both drugs produced significant falls in laying and standing, systolic and diastolic blood pressures. Although the hypotensive effects of methyldopa were more marked than tolamolol, these only achieved conventional (P〈0.05) levels of significance for lying blood pressure. There were no objective changes in haematological or biochemical indices during treatment with either drug, but patients complained of tiredness, weak limbs and mouth dryness significantly more during methyldopa treatment, than during either placebo or tolamolol therapy.
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  • 28
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    Once daily propranolol in the treatment of mild to moderate hypertension (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 163-166 
    Details
    ISSN: 1432-1041
    Keywords: Propranolol ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol was administered in a single dose of 80 mg, 120 mg, 160 mg, 240 mg, or 320 mg, to 23 patients with essential mild to moderate hypertension in a randomised, double-blind cross-over study. All treatments produced a significant fall in lying and standing blood pressures compared with placebo, but there was no statistically significant difference in the effects of the different doses. The percentage of patients showing a satisfactory fall in blood pressure was not different in the five treatment groups. The major anti-hypertensive effect of each dose was present by two weeks. The frequency of side-effects were similar on all the doses.
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  • 29
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    Influence of metoprolol, alone and in combination with a thiazide diuretic, on blood pressure, plasma volume, extracellular volume and glomerular filtration rate in essential hypertension (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 305-310 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; thiazides diuretics ; hypertension ; haemodynamic effects ; renal function ; body fluid volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In fifteen patients with essential hypertension WHO I–II (eight men and seven; mean age 45 years) blood pressure (BP), plasma volume (PV;125I-Albumin space), extracellular volume (ECV;82Brdistribution space) and glomerular filtration rate (GFR;51Cr-EDTA clearance) were measured before and during long-term antihypertensive therapy with metoprolol, alone, and in combination with thiazide diuretics. Metoprolol given alone to all patients for an average of 5 months (mean dose 230 mg) resulted in a reduction in systolic and diastolic pressure by 11% and 8%, respectively. In eight patients the BP reduction was considered inadequate (non-responders). In the group as a whole, ECV increased significantly by 5%. The increase in ECV in the non-responders was five times larger than in the responders (1.025 ml against 205 ml), which may in part account for the inadequate BP control. Addition of a thiazide diuretic for an average of 3.5 months resulted in reduction of ECV to its pretreatment level and a pronounced additional fall in BP, comparable to that in the responders. No systematic change in PV or GFR could be demonstrated. No difference was found between the two groups regarding sex, pretreatment BP, body fluid volumes or renal function. On average the non-responders were 20 years older than the responders. The clinical importance of the apparent age-related expansion of ECV and the mechanism behind fluid retention during antihypertensive treatment with beta-blocking drugs are discussed. As failure of BP control during treatment with beta-blockers may be due to fluid retention, concurrent use of diuretics is indicated.
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    URL: http://dx.doi.org/10.1007/BF00558432
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  • 30
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    Long-term clonidine effects on autonomic function in essential hypertensive man (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 25-32 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 ± 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104±5 to 84±3 mmHg;p〈0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; allp〉0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8±4.3 to 39.4±5.2 mmHg,p〈0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.
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  • 31
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    A clinical and pharmacokinetic evaluation of tolmesoxide in hypertensive patients (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 113-118 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; hypertension ; side-effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and a diuretic. After a 50 mg oral dose mean (± SD) peak plasma concentration of T was 1.13±0.29 µg/ml−1 and occurred 0.79±0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37±0.09 µg/ml−1 at 1.92±1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78±0.77 h and 10.78±7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50–200 mg t. i. d. During in-patient administration of 600–900 mg T daily (n=6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n=4) was associated with a significant fall in mean systolic but not diastolic bp (lying −15/+1 mm Hg. standing −25/−8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean ± SD) significantly from 55±5/min to 66±8/min following 900–1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600–900 mg daily eventually necessitated drug withdrawal. In its present from T is not recommended for the treatment of hypertension.
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    URL: http://dx.doi.org/10.1007/BF00568397
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  • 32
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    A controlled study of the antihypertensive effect of carteolol, a newβ-adrenergic receptor blocking drug, in combination with hydrochlorthiazide and amiloride (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 239-244 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of carteolol, a new β-blocking agent, added to basal diuretic treatment (hydrochlorthiazide 50 mg and amiloride 5 mg) has been assessed in a controlled trial in 17 patients with mild-to-moderate hypertension. The trial was divided into 4 stages: 1) run-in period with no antihypertensive treatment, 2) diuretic period (the diuretic being continued as basal treatment during the two following periods), 3) carteolol titration period, and 4) double-blind cross-over period comparing carteolol with placebo, which lasted 2 times 4 weeks. Although the diuretic effectively reduced the blood pressure, 17 of the 20 patients originally studied still had an elevated diastolic blood pressure (≧ 95 mmHg) after the diuretic period, thus fulfilling the inclusion criteria for the study. During the titration period carteolol 5 to 20 mg b. i. d. significantly reduced the elevated blood pressure. The blood pressure was reduced to normal in all 17 patients, although in two patients this occurred only during the double-blind period. During the double-blind period, the dose of carteolol was used which had given a satisfactory response during the titration period. The blood pressure in the 14 patients who completed the trial remained low both with carteolol and placebo during the double-blind stage, and was only slightly lower with carteolol than with placebo. This is probably due to a “carry-over” effect. Three patients discontinued the trial due to side effects (1 urticaria, 1 insomnia and 1 nausea) while on carteolol. There was no other difference between carteolol and placebo in the number or severity of side effects.
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    URL: http://dx.doi.org/10.1007/BF00562799
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    Chronic treatment with the new potent vasodilator Ro 12-4713 in moderate to severe hypertension: Effects on blood pressure, endocrine function, sodium and plasma volume (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 79-84 
    Details
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.
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    URL: http://dx.doi.org/10.1007/BF00607141
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    Serum lipoprotein changes during atenolol treatment of essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 335-338 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; atherosclerosis ; hypertension ; serum lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum lipoproteins were determined in 15 patients before and during antihypertensive treatment with atenolol 0.1–0.2 g/day for a mean of 8 months. The mean blood pressure fell from 171/103 to 154/93 mm Hg (p〈0.05). Significant lipoprotein changes were an increase in very low density triglycerides (VLDL-TG) from 1.21±0.95 (SD) to 1.62±1.24 mmol/l (p〈0.01) and in low density (LDL) TG from 0.46±0.12 to 0.51±0.12 mmol/l (p〈0.05). Together, these TG increases resulted in development of hypertriglyceridaemia in 7/15 patients during atenolol treatment. No effect on whole serum cholesterol or on the high density lipoprotein cholesterol concentrations were found. Thus, some patients on long term treatment with atenolol seem to receive the benefit of normotension at the cost of hypertriglyceridaemia. This may have practical implications, since hypertriglyceridaemia constitutes an important risk factor for atherosclerosis.
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    URL: http://dx.doi.org/10.1007/BF00615401
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    Prolactin secretion during reserpine and syrosingopine treatment (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 347-349 
    Details
    ISSN: 1432-1041
    Keywords: reserpine ; syrosingopine ; prolactin secretion ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 20 mild hypertensive women, reserpine induced a significant increase in mean plasma PRL, both under basal conditions (from 6.6±0.9 to 17.9±2.9 ng/ml), and on repeated determinations during the day. In contrast to reserpine, the administration of syrosingopine, a synthetic compound derived from reserpine, to the same subjects was not followed by a significant change in prolactin level. Beyond their pharmacological interest, these results are of clinical importance when considering that rauwolfia alkaloids are used for long term treatment, and that an increase in PRL levels is important in pathology, both in relation to the function of the hypophyseogonadal axis and in view of its possible facilitation of the growth and development of mammary cancer.
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    URL: http://dx.doi.org/10.1007/BF00615404
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    Long-term effects of captopril on renal function in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 315-323 
    Details
    ISSN: 1432-1041
    Keywords: captopril ; hypertension ; glomerular filtration ; para-aminohippuric acid ; renal function ; severe drug reaction ; nephrotic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of captopril up to 450 mg/day on blood pressure and renal function were investigated during sustained treatment of 10 patients whose severe hypertension had not responded to previous therapy. All the patients were kept on diuretics and most of them on β-blockers, too. A control determination of glomerular filtration rate (GFR) and para-aminohippuric acid clearance (CPAH) was performed during the prior treatment. The effect of the addition (or substitution) of captopril were assessed after an average of 25 days (short-term) and 26 weeks (long-term). Short-term treatment produced a 15.5% decrease in mean blood pressure and interindividually variable effects on renal function. On average GFR was somewhat lower and CPAH slightly higher than the control values (not significant). This pattern is quite similar to the effects of most other antihypertensive drugs. On long-term therapy GFR rose by a mean of 9% (NS) and CPAH by 17% (p〈0.02). However, in a patient who developed a captopril-induced nephrotic syndrome, GFR dropped to 56% and CPAH to 50% of the control values. In another patient a transient rise in serum creatinine accompanied a severe drug reaction.
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    Patient compliance and therapeutic coverage: comparison of amlodipine and slow release nifedipine in the treatment of hypertension (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 477-481 
    Details
    ISSN: 1432-1041
    Keywords: Amlodipine ; Nifedipine ; Compliance ; slow release formulation ; hypertension ; therapeutic coverage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To study patient compliance in hypertensive outpatients amlodipine (5 mg once daily) and slow release nifedipine (20 mg twice daily) were compared in an open, crossover study in general practices. Four methods of assessment for patient compliance (pill count, taking compliance, days with correct dosing, timing compliance) were used in both study arms. For the latter three assessment a special device, the medication event monitoring system, was used to record the time and date of each opening and closure of the container. The compliance of the 320 hypertensive patients with once-daily amlodipine was markedly superior to twice-daily slow release nifedipine. Therapeutic coverage was also significantly better for amlodipine in the hypertensive patients. Amlodipine was better tolerated than nifedipine slow release. Patient compliance and therapeutic coverage with the calcium antagonist amlodipine given once daily was superior to slow release nifedipine b. d. in hypertensive outpatients recruited in general practice. Statistical Unit: Léon Kaufmann, Marie-Paule Derde, Data Investigation Company Europe, Brussels Participating Investigators: D. Abbate, G. Armand, C.I. Authelet, J.L. Badot, J. Baeck, P. Baeck, P. Bastin, C.I. Bernard, P. Bernard, B. Beyssens, J. Bosly, P. Boudart, J. Bourdeaudhuy, W. Callens, L. Carolides, Y. Catry, E. Cerstelotte, F. Charlier, H. Charloteaux, J.M. Chaudron, L. Christiaen, G. Cornette, P. Cranskens, R. Creteur, N. De Cock, M. De Corte, A. De Vos, P. Defrance, P. Delhaye, G. Deneckere, M. Dobbeleir, A. Dufour, P. Dumont, L. D'Haen, H. D'Haenens, P. Eloy, P. Evrard, C. Fellemans, G. Geeraerts, L. Gielen, D. Grand, J. Grosjean, J. Guffens, R. Guillaume, R. Hacquaert, V. Hamoir, W. Hens, M. Hondeghem, M.C. Humblet-Koch, L. Leven, W. Janssens, L. Jeanfils, J. Jodogne, B. Jortay, W. Ketels, J.M. Krzesinski, E. Langendries, J. Lannoy, M. Leeman, J. Leire, P. Lempereur, L. Lenaerts, F. Lustman, R. Martens, Y. Maus, M. Meroueh, J.P. Meurant, P. Meurant, A. Michiels, E. Mievis, H. Moors, K. Naesens, P. Neels, J. Neven, W. Odeurs, W. Pardon, M. Peduzzi, J. Piette, D. Plessers, P. Putzeys, A. Quoidbach, A. Renaerts, G. Rits, M. Ruhwiedel, M. Salavracos, M. Seret, P. Sibille, M. Taziaux, J. Teucq, H. Therasse, F. Tihon, F. Vandenput, J. Van Elsen, J.P. Van Liefferinge, J. Van Neck, M. Van Pelt, T. Van Vlaenderen, G. Vandenbeylaardt, M. Vandewoude, F. Veldeman, D. Ven, F. Verbruggen, A. Vlaeminck, P. Werion, J. Westerlinck.
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    Interindividual variation in the enzymatic 15-keto-reduction of 13,14-dihydro-15-keto-prostaglandin E1 in human liver and in human erythrocytes (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 147-153 
    Details
    ISSN: 1432-1041
    Keywords: Key wordsProstaglandin E1 ; Carbonyl reductase; 13 ; 14-dihydro-15-keto-PGE1 ; 13 ; 14-dihydro-PGE1 ; human ; liver ; erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The therapeutic response to PGE1 is highly variable, and a contribution by variable formation of its active tertiary metabolite PGE0 is in question. Hence, the objective of this study was to assess the person-to-person variation of the reduction of the inactive intermediate metabolite 15-KD PGE1 by human liver and human erythrocytes in forming the active metabolite PGE0. Methods: Source of enzyme was lysed erythrocytes from 29 donors, and a bank of 37 donor livers including specimens from 15 children. Tritium-labelled 13,14-dihydro-15-keto-prostaglandin E1 (15-KD PGE1) was used at low nanomolar concentrations and found to be converted almost exclusively to the more polar compound 13,14-dihydro-prostaglandin E1 (PGE0) by an NADPH-dependent carbonyl reductase. The identity of the product PGE0 was established by comparison of its chromatographic and mass spectral characteristics with authentic PGE0. Results: Lysed erythrocytes had readily measurable enzymatic activity; differences between the preparations from 29 subjects were very small with only a twofold range of variation. In contrast to lysed erythrocytes, intact erythrocytes did not catalyse the reaction so that the erythrocyte activity should be medically immaterial. 15-KD PGE1 15-ketoreductase activity of liver cytosol averaged 61.1 fmol · min−1 · mg−1 protein in preparations from 37 human livers. Individual activities varied over an almost tenfold range, with indications of a non-normal distribution. Kinetic studies of selected specimens showed substantially different Vmax values but indistinguishable k M values, suggesting that the individual variation in 15-KD PGE1 15-ketoreduction is the result of differences in enzyme concentration rather than of structural enzyme variations. The activity in 15 livers from children was significantly lower than in those from adults. Inhibition data suggest that both the liver and the erythrocyte enzymes belong to the class of carbonyl reductases. Conclusions: The variations in hepatic enzyme activity may be expected to affect the transformation of 15-KD PGE1 to the active metabolite PGE0 in vivo. The clinical significance remains to be explored.
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    Effect of oral labetalol on plasma catecholamines, renin and aldosterone in patients with severe arterial hypertension (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 305-310 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; furosemide ; hypertension ; aldosterone ; blood pressure ; plasma catecholamines ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined α-and β-adrenergic receptor blockade induced by oral labetalol treatment for 2 months. Furosemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined α- and β-adrenergic receptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances the antihypertensive effect of labetalol, and partly modifies both renin and sympathetic nervous activity.
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    URL: http://dx.doi.org/10.1007/BF00605626
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    Multicentre comparative trial of tienilic acid and hydrochlorothiazide in hypertensive patients (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 319-322 
    Details
    ISSN: 1432-1041
    Keywords: tientilic acid ; hydrochlorothiazide ; hypertension ; diuretics ; hyperuricemia ; hypouricemic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty — eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, anti-hypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.
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    Antihypertensive effect of various doses of hydrochlorothiazide and its relation to the plasma level of the drug (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 195-201 
    Details
    ISSN: 1432-1041
    Keywords: Diuretics ; thiazides ; hydrochlorothiazide ; hypertension ; plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated hypertensive patients (WHO Stage I and II) were given hydrochlorothiazide (hct) 12.5, 25, 50 and 75 mg for two weeks after an initial four week period of placebo treatment. Blood pressure recordings were made casually and after 30 min rest in lying, sitting and standing positions. Plasma concentrations of the drug were measured by GLC. A significant decrease in BP was seen during treatment with hct 12.5 mg except in the casual standing position. Doubling of the dose twice produced very little further decrease in BP. The mean steady state concentration was 111 ng · ml−1 during treatment with hct 75 mg. A linear relationship was found between the plasma concentration of hct at 0 and 5 h and the various dose levels of hct. No relation was found between plasma concentration and reduction in blood pressure.
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    Fixed combination of sotalol and hydrochlorothiazide in the treatment of uncomplicated hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 395-401 
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    ISSN: 1432-1041
    Keywords: sotalol ; hydrochlorothiazide ; hypertension ; combination fixed ratio ; serum potassium ; long term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The combination of sotalol and hydrochlorothiazide in a fixed ratio of 6.4:1 was evaluated in thirty patients with uncomplicated hypertension. In the first part of the study, once daily administration of an optimal dose of the combination was significantly more effective than either hydrochlorothiazide or sotalol alone in lowering both the supine and standing systolic and diastolic blood pressure. Blood pressure was still controlled 24 h after the previous dose. Serum potassium fell by 0.37 mEq/l from the mean pretreatment value after treatment with the combination, but it still remained within the normal range. In the second part of the study the long term effect of the combination on blood pressure, heart rate and biochemical parameters was studied in twenty patients. Supine and standing blood pressure fell by 28.7/15.3 mmHg and 29.5/17.6 mmHg, respectively (p〈0.001). Serum potassium was 3.98±0.07 mEq/l after twelve months of therapy; potassium supplements were not administered. Like serum potassium, the other biochemical parameters remained within the normal range. The combination was well tolerated on long term use, and only one patient withdrew from the study.
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    Dissociation of biochemical and hypotensive effects of debrisoquine in hypertensive patients (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 81-86 
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    ISSN: 1432-1041
    Keywords: debrisoquine ; hypertension ; renin ; catecholamines ; platelet monoamine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were measured before and during chronic treatment with oral debrisoquine in 14 in-patients with essential hypertension. There was a significant fall (mean ±SD) in the 24 h urinary excretion of vanillylmandelic acid (15.3±2.8 to 6.7±1.9 µmol) noradrenaline (199.0±105.8 to 125.2±43.3 nmol) and plasma renin activity (0.71±0.47 to 0.40±0.20 pmol Angio I ml−1 h−1) while the urinary normetadrenaline/noradrenaline ratio increased (10.4±6.1 to 17.1±5.1). No significant change was seen in the output of adrenaline or of O-methylated metabolites. Debrisoquine produces extensive noncompetitive inhibition of platelet monoamine oxidase in vivo at low therapeutic plasma concentrations. These changes support the view that treatment with debrisoquine produces intraneuronal inhibition of monoamine oxidase and post-ganglionic blockage. There was a significant correlation between the change in standing diastolic blood pressure and the daily dose (rs=−0.52), pre-dose plasma concentration (rs=−0.85) and mean daily urinary recovery (rs=−0.80), of debrisoquine. The full extent of the biochemical changes were seen at low dose and low plasma concentration and were not directly correlated with the fall in standing or supine blood pressure.
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    Long-term hemodynamic effects of penbutolol at rest and during exercise in essential hypertension (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 149-153 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenergic blockade ; penbutolol ; haemodynamics ; hypertension ; prolonged treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen men with previously untreated essential hypertension (WHO Stage I) were studied as out-patients. Oxygen consumption, heart rate, cardiac index and brachial arterial pressure were recorded at rest supine and whilst sitting position, and during steady state exercise at 50, 100 and 150 W. The subjects were then treated with penbutolol 20–80 mg/day. In 12 responding patients hemodynamic study after 1 year demonstrated that systolic, diastolic and mean arterial pressure were reduced by approximately 20% at rest and 18% during exercise. Heart rate was reduced about 24% at rest and 26% during exercise. The stroke index did not show any significant change during rest, but during exercise the post-treatment values were 8%, 13% and 18% higher than the pre-treatment values at the 50, 100 and 150 W exercise levels, the last two changes being significant. Thus, the reduction in cardiac index during exercise was less than the reduction in heart rate — about 15%, but 24% when sitting at rest. The total peripheral resistance index did not show any significant change at rest or during exercise. Dizziness or muscular fatigue occurred in 6 patients during the first two weeks of treatment. From then on no side-effects were noted. It is concluded that the hemodynamic effects of longterm treatment with penbutolol in mild to moderate hypertension largely resemble those after the majority of other beta-blockers.
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    Role of various vasodepressor systems in the acute hypotensive effect of captopril in man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 1-8 
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    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; angiotensin ; renin ; aldosterone ; catecholamines ; prostaglandins ; kininase II ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute hypotensive effect of captopril 25 mg was investigated in 26 hypertensive patients (11 with essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril led to an increase in plasma renin activity, active and total plasma renin concentration and angiotensin I, a decrease in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2* and no change in plasma (nor)adrenaline, dopamine and inactive renin concentration. The hypotensive effect of captopril was related to the changes in plasma angiotensin II level and inversely to the change in prostaglandin E2; the correlation coefficients were low, respectively 0.61 and −0.44. It is likely that the acute hypotensive effect of captopril to some extent is related to changes in plasma angiotensin II and in prostaglandins E2 and F2*. There is no evidence for a role of the adrenergic systems in the hypotensive response.
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    Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 399-405 
    Details
    ISSN: 1432-1041
    Keywords: alpha-adrenergic blocker ; hypertension ; blood pressure ; pulse rate ; noradrenaline ; plasma renin activity ; plasma aldosterone ; dopamine-beta-hydroxylase ; E-643
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine whether E-643, a new α-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-β-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 → 151±28/89±14 mmHg), sitting (158±22/101±11 → 138±28/89±15 mmHg) and standing (153±32/103±21 → 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 → 69±10 beats/min), but was increased in the sitting (68±10 → 73±9 beats/min) and standing (73±10 → 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-β-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-β-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.
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    Chlorthalidone in mild hypertension — Dose response relationship (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 407-411 
    Details
    ISSN: 1432-1041
    Keywords: chlorthalidone ; hypertension ; dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The dose response curve for 25, 50, 75 and 100 mg doses of chlorthalidone was studied in double blind fashion over an 8 week period in patients who presented with untreated mild hypertension. One hundred and thirty four patients completed this multicentre, family practice study. After 2 week's medication, a decline in blood pressure was noted in all dosage groups and this was maximal by 4 weeks. At 8 weeks all doses of chlorthalidone induced a significant reduction in both systolic and diastolic blood pressures (mean −18 and −10 mmHg respectively). Amongst the 4 dosage groups, no differences in response were noted resulting in a flat dose response curve. During the study, mean blood urea and serum uric acid rose whilst serum potassium fell, the urea and potassium being least affected in the 25 mg dosage group. As the dosage of chlorthalidone increased, so the tendency for abnormal laboratory values increased. Unwanted effects sought during the study were relatively few in number. No clear dose response relationship was evident although the positive responses in the 25 mg dosage group were less than in the higher dosages. These results suggest that 25 mg chlorthalidone is the optimum dosage for initiation of therapy in patients with mild to moderate hypertension. This dosage is associated with less adverse biochemical changes and unwanted effects than the higher dosages studied.
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    The pharmacokinetics of trichlormethiazide in hypertensive patients with normal and compromised renal function (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 453-457 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; trichlormethiazide ; hypertension ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of trichlormethiazide (TCZ) was studied in twelve patients after a single 4 mg dose. Seven patients had normal renal function with creatinine clearances greater than 90 ml/min. Five patients had compromised renal function with creatinine clearances averaging 48±29 ml/min. The TCZ plasma half life and area under the plasma concentration-time curve (AUC) were significantly greater in patients with impaired function, compared to patients with normal renal function. There were no significant differences between the two patient groups in terms of either rate of drug absorption or total urinary recovery of unchanged drug. Furthermore, there was no correlation between peak drug levels or AUC and renal excretion of water or electrolytes.
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    Combination therapy in hypertension (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 1-8 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; combination therapy ; population survey ; drug treatment ; prescription patterns ; population incidence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a cross-sectional study, antihypertensive drug treatment was studied in a representative population sample of people aged 30–64 years, using a combination of postal survey, personal interview, clinical assessment and drug prescriptions. 11% of the men and 16% of the women were currently taking antihypertensives; 54% of patients used one, 38% used two, and 8% used three or more preparations. Men used slightly more drugs than women. Diuretics were used by 62% and betablockers by 49% of the sample population. Fixed combinations of thiazides and potassium-sparing agents formed 70% of all diuretic preparations used. Only 12% of the patients used fixed antihypertensive combinations, of which over half were diuretic-reserpine-vasodilator combinations; women and older patients used them most often. The most common freely combined preparations were diuretics and betablockers, which formed almost half of all two-drug combinations, and were also present in 70% of all triple combinations. Adequate control of blood pressure (DBP 〈100 mmHg) was achieved by slightly under 50% of the patients, the BP of women being more adequately controlled than that of men. Differences in BP control were found between the different drugs and combinations. Antihypertensive combination therapy is important in successful treatment, but we still cannot be sure whether fixed combination preparations or, as in this study, free combinations of marketed preparations are better alternatives for treatment.
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    Sotalol and metoprolol comparison of their anti-hypertensive effect (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 87-92 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; sotalol ; comparison ; plasma levels ; serum uric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 28 patients, aged 35–62 years, with uncomplicated hypertension, entered a double-blind, crossover study, in which the effects of single daily doses of sotalol and metoprolol were compared. Both drugs exerted a clinically useful anti-hypertensive effect as monotherapy, or in combination with a thiazide diuretic. No significant difference in hypotensive effects was noted between the two beta-blocking agents, when the dose was titrated to an optimal clinical effect. Treatment with sotalol and metoprolol was associated with a clinically insignificant increase in serum uric acid concentration. The side-effects observed were few, and in only two cases was therapy discontinued. We regard both sotalol and metoprolol as useful anti-hypertensive drugs.
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    The response to the angiotensin antagonist saralasin in predicting therapeutic outcome in hypertension treated with frusemide (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 165-168 
    Details
    ISSN: 1432-1041
    Keywords: frusemide ; saralasin ; hypertension ; reninangiotensin ; sodium ; diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of tests of the renin-angiotensin system for predicting antihypertensive responses to frusemide combined with dietary sodium deprivation was evaluated in eighteen patients with severe hypertension. No relationship could be shown between changes in blood pressure induced by the angiotensin analogue, saralasin, and the short-term or long-term therapeutic effects of diuretic- and diet-induced sodium depletion. Mean values for saralasin response and initial plasma renin activity in eight patients whose blood pressure was adequately controlled by therapeutic sodium depletion were closely similar to those obtained in the remaining ten patients, who proved refractory to this treatment.
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    URL: http://dx.doi.org/10.1007/BF00627914
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    Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; insulin sensitivity ; pancreatic beta-cell function ; hypertension ; propranolol ; atenolol ; insulin secretion ; plasma GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
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    URL: http://dx.doi.org/10.1007/BF00546701
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    Should the acetylator phenotype be determined when prescribing hydralazine for hypertension? (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 39-42 
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    ISSN: 1432-1041
    Keywords: acetylator phenotype ; hydralazine response ; hypertension ; blood pressure control ; lupus syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and β-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p〈0.01). Despite higher doses of hydralazine the blood pressure was controlled in only 27% of rapid acetylators compared to 65% of slow acetylators (p〈0.02). The relation of acetylator phenotype to blood pressure response was statistically independent of initial blood pressure, age, sex, body weight and serum creatinine (p〈0.005). Current recommendations on hydralazine dosage are unsatisfactory for the 40% of hypertensive patients who are rapid acetylators. We suggest measurement of the acetylator phenotype in patients who respond incompletely to 200 mg hydralazine daily. About 70% of these patients will be rapid acetylators in whom the dose of hydralazine can be increased safely.
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    Comparison of methods to detect side-effect on clinical application of chloranolol, a beta-adrenergic receptor inhibitor (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 555-562 
    Details
    ISSN: 1432-1041
    Keywords: Tobanum® ; beta-blocker ; chloranolol ; hypertension ; angina pectoris ; arrhythmia ; detection methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The incidence of side-effects on administration of chloranolol (Tobanum®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.
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    Propranolol vs metoprolol vs labetalol: A comparative study in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 1-6 
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    ISSN: 1432-1041
    Keywords: hypertension ; beta-blockers ; propranolol ; metoprolol ; labetalol ; exercise ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.
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    Reduced peripheral vascular symptoms in elderly patients treated with α-methyldopa — A comparison with propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 325-329 
    Details
    ISSN: 1432-1041
    Keywords: alpha-methyldopa ; propranolol ; hypertension ; side effects ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.
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    Effect of indapamide on renal plasma flow, glomerular filtration rate and arginine vasopressin in plasma in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 543-547 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; glomerular filtration ; arginine vasopressin ; free water clearance ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal plasma flow (RPF), glomerular filtration rate (GFR), arginine vasopressin in plasma (AVP), free water clearance ( $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ ) and blood pressure (BP) were determined in 11 patients with essential hypertension at the end of 3 consecutive periods of observation each of 6 of weeks duration; indapamide 2.5 mg daily was given in period 2 and placebo in periods 1 and 3. RPF and GFR were reduced by 9% and BP by 9%/14% supine and 14%/12% standing during indapamide treatment. Changes in renal haemodynamics were not correlated with those in BP. AVP was not significantly altered by indapamide and was not correlated with BP. Indapamide reduced $${\text{C}}_{{\text{H}}_{\text{2}} {\text{O}}}$$ possibly due to the reduction in GFR. It is concluded that indapamide evidently induces redistribution of the cardiac output, with enhanced muscle blood flow and reduced renal perfussion, and that AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension under basal conditions.
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    Is the feeling of cold extremities experienced by hypertensive patients due to their disease or their treatment? (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 47-49 
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    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients' age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
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    Long acting nifedipine in the treatment of severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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    Evidence for a peripheral component in the sympatholytic actions of clonidine and guanfacine in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 23-27 
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    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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    Crossover comparison of moxonidine and clonidine in mild to moderate hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 147-152 
    Details
    ISSN: 1432-1041
    Keywords: moxonidine ; clonidine ; hypertension ; double-blind crossover ; side-effects ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of moxonidine·HCl·H2O (MOX) was compared with that of clonidine·HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154–178/96–108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2–0.4 mg of either agent caused a significant decrease in BP (p〈0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. −10/−14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. −10/−15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p=0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p〈0.01, diastolic BP p〈0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p=0.003).
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    Systemic and cardiac haemodynamic interactions between guanfacine and hydrallazine in hypertensive patients (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 393-396 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; hydrallazine ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiac and systemic haemodynamics ; blood pressure ; limb blood flow ; limb vascular resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of guanfacine and hydrallazine on cardiovascular haemodynamics and on sympathetic nervous activity has been studied in 16 patients with essential hypertension. Two groups of patients were investigated: in Group A guanfacine brought the blood pressure back to normal (diastolic blood pressure ⩽90 mmHg), and in Group B diastolic blood pressure was 〉 90 mmHg and required the addition of hydrallazine. Guanfacine significantly decreased heart rate, plasma renin activity and urinary excretion of noradrenaline, without altering cardiac contractility. In Group B, guanfacine 2 to 6 mg/day produced a significant decrease in blood pressure from 178.7/112.4 to 164.4/102.9 mmHg and in heart rate from 77.1 to 62.7 beats/min after 4 weeks of treatment. Guanfacine did not significantly alter preejection period, cardiac output or total peripheral resistance. Hydrallazine 50 to 300 mg/day caused a further reduction in blood pressure from 164.4/102.9 to 150.7/90.2 mmHg and an increase in heart rate from 62.7 to 72.1 beats/min. Limb blood flow was increased from 4.55 to 5.93 ml/100 g/min and limb vascular resistance was decreased from 39.55 to 23.6 mmHg 100 g·min/ml. Hydrallazine also caused a slight increase in plasma renin activity and urinary excretion of noradrenaline. It is concluded that guanfacine is a useful agent to block a hydrallazine-induced increase in sympathetic nervous activity.
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    Piretanide, a potassium stable diuretic, in the treatment of essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; triamterene ; double blind comparison ; potassium ; magnesium ; side-effects ; serum electrolytes ; serum parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, double blind, parallel group study in out patients with mild to moderate essential hypertension the effects of piretanide on serum electrolytes and on blood pressure were compared with those of triamterene alone and the combination piretanide + triamterene. 136 patients entered the study; 18 patients did not fulfill the inclusion criteria (RRdiast was below 95 mmHg or above 120 mmHg) at the end of the placebo period, 6 dropped out due to side effects, and 1 due to lack of efficacy. Data from 1 patient were not evaluated because the patient did not come regularly for checkups. The results for 110 patients were analyzed. Piretanide 6 mg b.d. and piretanide 6 mg + triamterene 50 mg b.d. produced a significant reduction both in supine and erect blood pressure, which was evident at 2 weeks and which increased over the ensuing 12 week trial period. A mean maximal fall of 16.5% was noted in the piretanide group and 15% in the piretanide + triamterene group. Triamterene alone (50 mg b.d.) also reduced diastolic and systolic blood pressures but the reduction was significantly less (diastolic blood pressure) than in both the piretanide groups, and it showed a more rapid return to pretreatment level during a placebo washout phase at the end of the study. A reduction in standing diastolic blood pressure below 95 mmHg was attained in 84% of patients in the piretanide group, 82% in the piretanide + triamterene group and in only 58% of the triamterene group. There were no significant changes within groups nor differences between the three groups in serum potassium or magnesium. 7 patients were withdrawn from the study because of side-effects due to too marked a clinical action (polyuria, orthostatic disorders and hypotension), one from the piretanide group, and the others in the piretanide + triamterene group. One patient in the triamterene group left the study prematurely due to the lack of effect.
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    Double-blind comparison of once-daily bopindolol, pindolol and atenolol in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 529-534 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoceptor blocking agents ; hypertension ; adverse reactions ; atenolol ; bopindolol ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of once-daily bopindolol, a nonselectiveβ-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.
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    Long term treatment of moderate hypertension with the beta1-receptor blocking agent metoprolol (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 247-254 
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    ISSN: 1432-1041
    Keywords: Beta1-receptor blockade ; metoprolol ; hypertension ; submaximal work ; insulin-induced hypoglycaemia ; plasma catecholamines ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of submaximal work and insulin-induced hypoglycaemia on plasma catecholamines and renin activity was studied in nine males with moderate hypertension before treatment, after one month on placebo and after three months of metoprolol treatment. The maintenance dose used was 50–150 mg three times daily. The placebo caused no change in blood glucose, blood pressure, pulse rate, plasma catecholamines and renin activity, neither under basal conditions nor following submaximal work or insulin-induced hypoglycaemia. Metoprolol significantly reduced blood pressure, pulse rate and plasma renin activity under basal conditions whereas plasma catecholamines were unchanged. During metoprolol treatment the increase in blood pressure and pulse rate in response to submaximal work was reduced, but the plasma noradrenaline response was enhanced and plasma adrenaline unaltered. The decrease in pulse rate after work was positively correlated with the mean plasma metoprolol concentration. The fall in blood glucose after insulin 0.1 IU/kg body weight i. v. and its return to normal was unaffected by metoprolol. Before metoprolol, hypoglycaemia was followed by a pronounced increase in plasma adrenaline, with a maximum after 45 min. During metoprolol the adrenaline increase was even more pronounced. Hypoglycaemia was also followed by a two-fold increase in plasma noradrenaline, both before and during treatment with metoprolol. Plasma renin activity during submaximal work and insulin-induced hypoglycaemia varied as much before as during treatment with metoprolol.
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    Double-blind comparison of metoprolol, alprenolol, and oxprenolol in hypertension (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 369-374 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; alprenolol ; oxprenolol ; hypertension ; double-blind trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind comparison of the β-blockers metoprolol, alprenolol and oxprenolol was carried out to evaluate their antihypertensive effect and tolerability. 105 patients with previously untreated hypertension entered the trial and 71 completed it. Side-effects were infrequent and were never the reason for drop-out. All three drugs caused a statistically significant reduction in blood-pressure at the lower of the two doses used during a dose-finding period. At the higher dose employed in this period, metoprolol caused a significantly greater reduction in diastolic blood-pressure than did alprenolol or oxprenolol. All three drugs caused a significant reduction in heart rate. During the follow-up period, the β-blockers were supplemented if necessary with hydrochlorothiazide. This was required less frequently in the metoprolol group than in the other two groups.
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    URL: http://dx.doi.org/10.1007/BF00568195
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    Hypotensive action and side-effects of flutonidin in normal subjects (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 375-379 
    Details
    ISSN: 1432-1041
    Keywords: flutonidin ; clonidine ; hypertension ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind study, planned as a 7×7 latin square, three oral doses of futonidin (0.5, 1, 2 mg), of clonidine (0.0075, 0.150, 0.300 mg) and of a placebo were administered to 7 normal volunteers on 7 different treatment days, with an interval of 3 days. On each treatment day sitting blood pressure, heart rate and reaction time were measured, and sedation and dry mouth evaluated before and 1, 2, 3, 4, 6, and 8 h after administration. The placebo did not modify the basal value of any variable. Flutonidin and clonidine produced dose-related effects on blood pressure, heart rate, sedation and dry mouth, but did not influence reaction time. Analysis of the dose-response curves demonstrated that the effect of flutonidin was one-fifth to one-twelfth that of clonidine, depending on which variable was considered.
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    Long term treatment of moderate hypertension with the beta1-receptor blocking agent metoprolol (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 239-245 
    Details
    ISSN: 1432-1041
    Keywords: Beta1-receptor blockade ; metoprolol ; hypertension ; plasma catecholamines ; plasma renin activity ; urinary aldosterone ; plasma volume ; working capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine males with moderate hypertension were investigated before treatment, after one month on placebo and after three months on the beta1-receptor blocking agent metoprolol, 50–150 mg three times daily. During the placebo period no changes were observed apart from a slight decrease in supine pulse rate. Treatment with metoprolol significantly decreased blood pressure, pulse rate and plasma renin activity in the supine and upright positions. The efficiency of the drug on blood pressure was not correlated with pretreatment pulse rate or plasma renin, noradrenaline or adrenaline. The plasma concentration of metoprolol was related to the dose administered. With the patient supine, the decrease in plasma renin activity was correlated with the plasma concentration of metoprolol but there was no effect on plasma catecholamines. On standing, plasma noradrenaline increased significantly and to the same extent under all three conditions studied. During metoprolol treatment there was a non-significant tendency for urinary aldosterone in the entire group to decrease. However, in individual patients during metoprolol treatment urinary aldosterone showed a decrease which was significantly related to the decrease in plasma renin activity. Plasma volume rose slightly in patients on metoprolol. The treatment had no effect on maximal working capacity, measured by cycling on a stationary ergometer, but the associated increase in blood pressure and pulse rate was markedly reduced. Metoprolol was well tolerated and no side effects were observed.
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    Controlled trial of acebutolol in hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 89-92 
    Details
    ISSN: 1432-1041
    Keywords: Acebutolol ; hypertension ; controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acebutolol, a new cardioselective beta-adrenoceptor blocking agent, has been evaluated for the treatment of hypertension. Thirty eight previously untreated male patients with essential hypertension received placebo treatment during a 4-week run-in period, and then they were randomly (double-blind) allocated either to continued placebo treatment for three 4-week periods or to treatment with acebutolol 400, 600 and 1200 mg daily, respectively, for three 4-week periods. Blood pressure and heart rate were recorded at the end of each 4-week period. Treatment with acebutolol produced statistically significant reductions in blood pressure and heart rate as compared to the placebo regimen.
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    URL: http://dx.doi.org/10.1007/BF00645127
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    Effect of metoprolol on blood glycerol, free fatty acids, triglycerides and glucose in relation to plasma catecholamines in hypertensive patients at rest and following submaximal work (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 5-8 
    Details
    ISSN: 1432-1041
    Keywords: Beta1-receptor blockade ; metoprolol ; hypertension ; submaximal work ; plasma catecholamines ; free fatty acids ; glycerol ; triglycerides ; blood sugar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Studies were performed in nine male patients with moderate hypertension. Treatment with metoprolol, 50–150 mg three times daily for 4–17 weeks, had no effect on the plasma level of glycerol, free fatty acids, triglycerides or glucose under basal conditions, neither in the supine nor in the upright position. Submaximal work, performed postprandially, increased plasma glycerol before medication but not during metoprolol, in spite of a marked increase in plasma noradrenaline. The work load employed caused no change in free fatty acids, triglycerides or glucose, neither before medication nor during metoprolol.
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    URL: http://dx.doi.org/10.1007/BF00606673
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    Pharmacokinetics of bendroflumethiazide in hypertensive patients (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 119-124 
    Details
    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; pharmacokinetics ; hypertension ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml−1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg−1. Non-renal clearance averaged 200 ml · min−1. The renal clearance of bft was significantly lower (p〈0.05) after 5 mg (48 ml · min−1) than after 2.5 mg bft (93 ml · min−1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.
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    Timolol and bendrofluazide in the management of hypertension in general practice (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 319-324 
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    ISSN: 1432-1041
    Keywords: Timolol ; bendrofluazide ; hypertension ; general practice ; once daily dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The beta-adrenergic blocking drug, timolol, was combined with bendrofluazide in a comparative trial between once and twice daily dosage, conducted on 51 patients suffering from hypertension seen in general practice. During the initial control period seven of these patients became normotensive, leaving 44 who entered the trial. Using a cross-over design, treatment was continued for a total period of up to 16 weeks. With both dose regimes, systolic and diastolic pressures were rendered normotensive in over three-quarters of the patients, significant reductions occurring within the first two to four weeks of treatment.
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    Acebutolol in hypertension: Relationships between drug concentration and effects (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 383-390 
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    ISSN: 1432-1041
    Keywords: Acebutolol ; N-acetyl metabolite ; drug plasma concentrations ; plasma renin activity ; hypertension ; β-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. In an acute study (N=7) 400 mg oral acebutolol produced similar peak plasma levels of Ac and Am but Am had a longer half life. Group mean pulse and blood pressure fell significantly, although the size of individual blood pressure fall varied five-fold. There was no significant change in plasma renin activity. Correlations were found between drug concentration and β-blockade, assessed as % reduction in exercise tachycardia, and between both of these and the fall in post exercise systolic blood pressure. Similar comparisons were made in a chronic optimum dose study (N=11) both pre-dose and three hours post-dose. Am concentration was consistently higher than Ac at both times. Blood pressure was lowered equally pre-and post-dose when compared to placebo and plasma renin activity (PRA) was reduced on active treatment. Correlations were again shown between drug concentrations and β-blockade but none were found with changes in blood pressure or PRA. Between subject differences in blood pressure response could not be fully explained in terms of the other measurements but it is unlikely that pharmacokinetic differences are the major source of this variability.
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    Beta-adrenergic blockade in stress protection. Limited effect of metoprolol in psychological stress reaction (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 391-398 
    Details
    ISSN: 1432-1041
    Keywords: Beta-adrenergic blockade ; metoprolol ; mental stress ; vigilance ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a model system the influence of mental stress on blood pressure and heart rate was studied in normal persons and in patients with hypertension (WHO grade I–II). Metoprolol was employed to investigate the preventive effect of β-adrenergic blockade on the response to stress. In all groups blood pressure increased significantly during mental stress. The effect was not inhibited by metoprolol. The rise in heart rate, however, was depressed by β-blockade. Reaction time, opticomotor coordination and concentration ability were studied as parameters of vigilance, but no significant difference between the metoprolol and control groups were observed. Thus, metoprolol only influenced the heart rate in mental stress and it did not affect vigilance.
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    Comparison of once and twice daily administration of sotalol in the treatment of hypertension (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; once and twice daily dose ; three daily BP-readings ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty patients with mild to severe essential hypertension, satisfactorily controlled by twice daily Sotalol 80 to 320 mg/day, entered a double-blind, crossover study comparing the efficacy, tolerability and safety of their usual twice daily dose of Sotalol with the same total dose given once daily. Each double-blind period was eight weeks long; during it blood pressure and pulse rate were measured in each patient's home at 8–10 a. m., 12-2 p. m. and 8–10 p. m., on alternate days during the last week of each treatment period. There was no significant difference in blood pressure or pulse rate between each regime for the three readings during the day. The mean serum concentration of Sotalol twenty-four hours after once daily administration was not significantly lower than the concentration 12 h after twice daily administration. Once daily dosage did not cause any problems of tolerance.
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    Antihypertensive and hormonal effects of single oral doses of Captopril and Nifedipine in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 157-161 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; nifedipine ; plasma renin activity ; aldosterone ; vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W. H. O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: −23±2% at 37±15 min and −17±1% at 86±25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.
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    Use of labetalol in hypertensive patients during discontinuation of clonidine therapy (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 237-240 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; adverse effects ; plasma catecholamines ; plasma cAMP ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven hypertensive patients in whom clonidine therapy had to be discontinued, were treated prophylactically with labetalol, in order to avoid a possible hypertensive crisis. Most of the known side effects, which are consistent with the withdrawal phenomenon were observed, e.g. tremor, insomnia and apprehension, but headaches and flushing did not occur. Blood pressure levels remained unchanged, despite up to a 20-fold increase in plasma catecholamines. The lack of change in serial measurements of plasma cyclic AMP level appears to indicate that adequate adrenergic blockade was induced by labetalol. Since labetalol is a potent anti-hypertensive drug, and is also effective in avoiding a possible hypertensive crisis due to withdrawal of clonidine, we propose to use it as the drug of choice whenever discontinuation of clonidine therapy is indicated.
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    Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 251-258 
    Details
    ISSN: 1432-1041
    Keywords: aldosterone ; hypertension ; propranolol ; blood pressure ; plasma level ; renin ; urine level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg×4 (Group 1), 80 mg×4 (Group 2) and 160 mg×4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA and PAC fell in all groups, and remained reduced during C and D in Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin-aldosterone system was initially suppressed in all groups, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.
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    Effect of minoxidil on sympathetic nervous activity in clonidine-treated hypertensive patients (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 259-262 
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    ISSN: 1432-1041
    Keywords: clonidine ; minoxidil ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiovascular responses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of clonidine and minoxidil on sympathetic nervous activity has been studied in 10 patients with accelerated or resistant hypertension. Clonidine 150 to 900 µg/day caused a significant decrease in blood pressure of 18.6 mm Hg, of heart rate 16.4 beats/min, or plasma renin activity 1.13 ng/ml·h, and of urinary noradrenaline excretion 11.55 µg/day, and a significant lengthening of the pre-ejection period of 12.4 ms. Minoxidil 5 to 22.5 mg/day caused a further significant decrease in blood pressure of 24.2 mm Hg, and significant increases in heart rate 8.2 beats/min, plasma renin activity 1.68 ng/ml·h, and of urinary noradrenaline excretion 5.0 µg/day, and a significant shortening of the pre-ejection period of 20.6 ms. Neither clonidine nor minoxidil altered plasma dopamine β-hydroxylase activity or the cardiovascular responses to treadmill exercise. It is concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.
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    Use of fixed doses of beta blocking drugs in the treatment of hypertension (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 93-96 
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    ISSN: 1432-1041
    Keywords: atenolol ; penbutolol ; hypertension ; beta-blockers ; intrinsic sympathomimetic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Atenolol 100 mg and penbutolol 40 mg given once a day were both effective in controlling moderate hypertension, as judged by a randomised controlled, double-blind trial in 45 patients treated for six weeks. Both drugs significantly reduced the resting supine and erect blood pressures. No serious adverse effects could be attributed to either drug. Bradycardia occurred more frequently with atenolol than with penbutolol. Penbutolol, which possesses intrinsic sympathomimetic activity, may be useful in the treatment of patients in whom some other beta-blocker has failed to bring about adequate control of the blood pressure, despite marked bradycardia.
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    Comparison of hydrochlorothiazide and atenolol as initial treatment in uncomplicated hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 157-162 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; hydrochlorothiazide ; atenolol ; side effects ; therapeutic efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n=59) or 100 mg atenolol (n=60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP⩽90 mmHg (p〈0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP⩽90 mmHg (p〈0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still⩽90 mmHg. Non-responders to either medication were given the combination (n=46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure ⩽90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension.
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    Pharmacokinetics and hypotensive effect in healthy volunteers of pinacidil, a new potent vasodilator (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 603-608 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; pinacidil pyridine-N-oxide ; urinary excretion ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7±6.0 mmHg. Maximum rise in heart rate was 23.8±6.6 beats/min. Pinacidil serum distribution half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\alpha }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\alpha }$}}}$$ ) was 13.4±8.5 min and elimination half-life ( $${\text{T}}_{{\raise0.7ex\hbox{${\text{1}}$} \!\mathord{\left/ {\vphantom {{\text{1}} {{\text{2}}\beta }}}\right.\kern-\nulldelimiterspace}\!\lower0.7ex\hbox{${{\text{2}}\beta }$}}}$$ ) was 2.13±0.49 h. The apparent volume of distribution (Vdβ) was 90.3±13.21 and total body clearance was 31.1±9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40–400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 ± 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6±9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.
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    Pharmacokinetics of endralazine (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 661-661 
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    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; elimination half-liefe ; compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    Long acting nifedipine in the treatment of severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 13-17 
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    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure decrease ; drug combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The medication of patients receiving hydralazine, captopril and minoxidil was replaced by a new galenical form, long-acting nifedipine. An additional decrease in blood pressure was observed in most of the patients. Renal function was maintained in all of them. Adverse reactions may be reduced by the use of long-acting nifedipine, which would permit a reduction in the dosage of captopril and minoxidil.
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    URL: http://dx.doi.org/10.1007/BF00553147
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    Evidence for a peripheral component in the sympatholytic actions of clonidine and guanfacine in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 23-27 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; alpha2-adrenoceptors ; blood pressure ; clonidine ; guanfacine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of the changes in plasma growth hormone and noradrenaline concentrations in response to 15 min infusions of clonidine 0.2 mgs and guanfacine 2 mgs, were studied in six normal volunteers, in a double-blind, randomised, crossover study. Plasma noradrenaline fell within 15 min of the commencement of drug administration, by 36±14% after clonidine (p〈0.05) and by 32±11% (p〈0.05) after guanfacine. Plasma growth hormone was not significantly elevated until the 30th minute to 12.0±4.7 lU/ml (p〈0.05) after clonidine and 14.7±11.5 lU/ml (p〈0.05) after guanfacine, having been undetectable prior to both drugs. The reduction in plasma noradrenaline by these α2-adrenergic agonists, prior to activation of central adrenoceptors as detected by changes in plasma growth hormone, is evidence for a peripheral component in their sympatholytic effect.
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    URL: http://dx.doi.org/10.1007/BF00553149
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    Is the feeling of cold extremities experienced by hypertensive patients due to their disease or their treatment? (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 47-49 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; ISA ; CS ; cold extremities
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Patients with essential hypertension were interviewed prior to entering therapeutic studies in general practice. Patients’ age, sex and details of antihypertensive therapy (if any) were noted, as were their spontaneously reported symptoms. Complaints of cold extremities were highest in those taking a beta-blocker (4.1%). Those untreated or taking other therapies complained less often. Those patients taking a beta-blocker with ISA complained less often (3.1%) of cold extremities than those taking a beta-blocker without ISA (5.2%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395205
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    Pinacidil, a new vasodilator, in the treatment of patients with moderate to severe hypertension (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 287-289 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilator ; patients ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new vasodilator drug, pinacidil, N″-cyano-N-4-pyridyl-N′-1, 2,2-trimethylpropylguanidine, was studied in an open trial in 15 patients with moderate to severe hypertension. Four patients received pinacidil monotherapy, and in 11 patients it was used with a diuretic or a beta-blocker. In all but one patient normotension was achieved with a mean daily pinacidil dose of 46.7 mg b.i.d. (range 20–100 mg). Side effects were few and were action-related. There was no evidence of early toxicity. Pinacidil is a promising new antihypertensive vasodilator, which deserves further clinical evaluation.
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    URL: http://dx.doi.org/10.1007/BF00542161
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    Comparative study of DNA adducts levels in white sucker fish (Catostomus commersoni) from the basin of the St. Lawrence River (Canada) (1995)
    Springer
    Molecular and cellular biochemistry 148 (1995), S. 133-138 
    Details
    ISSN: 1573-4919
    Keywords: DNA adducts ; liver ; fish ; 32P-postlabelling ; polycyclic aromatic hydrocarbons ; genotoxic biomarker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The levels of DNA adducts in the hepatic tissue of the white sucker fish speciesCatostomus commersoni were determined by32P-postlabelling. The fish were caught at four sites: two sites near the city of Windsor (Québec, Canada) on the St. François River, a downstream tributary of the St. Lawrence River, and two sites in the St. Lawrence River itself, near the city of Montréal (Québec, Canada). The latter sites are known to be contaminated by many pollutants including polycyclic aromatic hydrocarbons. Total adduct levels in all fish ranged from 25.1–178.0 adducts per 109 nucleotides. White sucker from the selected sites of the St. Lawrence River had a significantly higher mean level of DNA adducts than those of the St. François River (129.4 vs 56.8, respectively). These results suggest that the effluents of many heavy industries (e.g. from a Soderberg aluminium plant) flowing in the St. Lawrence River are more likely to produce genotoxic damage to fish than those released in one of its tributary, and mainly associated to the activities of a small town and a nearby pulp and paper mill.
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    URL: http://dx.doi.org/10.1007/BF00928150
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    Genetics of aryl hydrocarbon hydroxylase induction in mice: Response of the lung to cigarette smoke and 3-methylcholanthrene (1977)
    Springer
    Biochemical genetics 15 (1977), S. 723-740 
    Details
    ISSN: 1573-4927
    Keywords: aryl hydrocarbon hydroxylase, gene loci controlling ; cigarette smoke ; mice ; lung ; liver ; 3-methylcholanthrene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract When mice from different inbred strains are injected intraperitoneally with 3-methylcholanthrene (MC), the activity of aryl hydrocarbon hydroxylase (AHH) rapidly increases in livers of some strains but not others. AHH plays a role in the metabolism of polycyclic hydrocarbons. Alleles at a small number of loci account for most of the variation in inducibility of hepatic AHH among mice, when MC is used as the inducing agent. Cigarette smoke is a common source of carcinogenic polycyclic hydrocarbons in the environment. Since some of the hydrocarbons in cigarette smoke are metabolized by AHH, the activity of AHH in tissues may affect the carcinogenicity of smoke in those tissues. The purpose of these experiments was to see whether induction of AHH in lung in response to cigarette smoke is regulated by the same genes that regulate induction of AHH in liver in response to MC. Mouse strains AKR/J and C57L/J and six recombinant inbred (RI) lines derived from them were tested for the response of AHH in lung and liver to parenteral MC or inhalation of cigarette smoke. Inducibility (the ratio of MC-induced AHH activities to basal AHH activities) in liver from MC-treated RI lines is bimodal and compatible with Mendelian segregation of genes at a small number of loci. Increased activities of AHH in MC-treated liver are associated with increased ability to metabolize BP and whole smoke condensates to mutagens detected by Salmonella typhimurium TA1538. Inducibility of AHH in lung in response to MC is not bimodal, and no definite conclusion about the number of loci can be made. When actual levels of AHH activity are considered, following the administration of MC as inducing agent, there is a correlation (r=0.89, p〈0.01) between AHH levels in liver and lung, suggesting that some genes affecting liver also affect lung. Basal and MC-induced AHH levels in lung are also correlated (r=0.86, p〈0.01). Mice with high basal activities have two to threefold higher levels of AHH after MC treatment than do mice with low basal activities. Induction of AHH in pulmonary tissues occurs in all mice after either parenteral MC or smoke inhalation. In contrast to MC treatment, AHH activities in lungs following smoke inhalation are not correlated with AHH levels in liver after MC (r=0.49) and are only weakly correlated with basal (r=0.66, 0.05〈p〈0.10) pulmonary levels. The correlation between MC-induced and smoke-induced AHH activities in lung is weak (r=0.63, 0.05〈p〈0.10). We conclude that the genetic regulation of AHH activity in lung is not as simple as the genetic regulation of AHH activity in liver, especially when complex inducing agents such as cigarette smoke are used.
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    URL: http://dx.doi.org/10.1007/BF00484100
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    Relationship between elevated lipid peroxides, vitamin E deficiency and hypertension in preeclampsia (1995)
    Springer
    Molecular and cellular biochemistry 151 (1995), S. 33-38 
    Details
    ISSN: 1573-4919
    Keywords: preeclampsia ; vitamin E ; lipid peroxidation ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and any relationship between the elevated MDA and lower vitamin E levels with hypertension in pregnant women. EDTA-Blood was collected from pregnant women at the time of delivery. Plasma vitamin E was determined by HPLC; MDA by the thiobarbituric acid-reactivity. Subjects with diastolic blood pressure(DBP) ≥90 mm Hg were considered hypertensive (HT) and with 〈90 mm Hg normotensive (NT). Data (Mean±SE) from 49 NT and 11 HT women show that HT has significantly lower vitamin E (22±1 vs 27±1 nmole/ml, p〈0.03) and elevated MDA levels (0.56±0.06 vs 0.43±0.02 nmole/ml, p〈0.03) compared to NT; the ages and gestational ages of women were similar. Among all women, there was a significant positive relationship between DBP and MDA levels (r=0.27, p〈0.05), and a significant negative relationship between vitamin E levels and DBP (−0.36, p〈0.005), and a significant negative relationship between MDA and vitamin E levels (r=−0.27, p〈0.05). Thus, HT women's plasma has significantly lower E and higher MDA levels, and DBP significantly correlates with the extent of vitamin E deficiency and increased MDA levels. This study suggests a relationship between elevated lipid peroxidation and lower vitamin E levels and hypertension in pregnancy (preeclampsia).
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    URL: http://dx.doi.org/10.1007/BF01076893
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    Influence of spontaneous hypertension on n-3 delta-6-desaturase activity and fatty acid composition of rat hepatocytes (1995)
    Springer
    Molecular and cellular biochemistry 152 (1995), S. 7-12 
    Details
    ISSN: 1573-4919
    Keywords: hepatocytes ; hypertension ; age ; desaturase ; essential fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The first and rate limiting step in the conversion of alpha-linolenic acid is catalyzed by the delta-6-desaturase enzyme. The activity of such an enzyme was studied in order to investigate the n-3 Polyunsaturated Fatty Acid biogenesis during hypertension. Rat isolated hepatocyte n-3 delta-6-desaturase activity was higher in 1 month old Spontaneously Hypertensive Rats — prehypertensive period- as compared to normotensive Wistar Kyoto rats, whereas there was no significant difference at 12 months — hypertensive period-. Our data indicate no correlation between the directly measured enzyme activity and the changes in hepatocyte n-3 fatty acid compositions. The loss of hepatocyte n-3 delta-6-desaturase activity in the Spontaneously Hypertensive Rat may be a key factor in the evolution of hypertension related to aging through altering the eicosanoid balance.
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    URL: http://dx.doi.org/10.1007/BF01076458
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    In vivo modulation of N-myristoyltransferase activity by orthovanadate (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 151-155 
    Details
    ISSN: 1573-4919
    Keywords: sodium orthovanadate ; diabetes ; N-myristoyltransferase ; liver ; membrane-associated ; vanadate ; obese Zucker rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract N-Myristoyltransferase (NMT) catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of several proteins and are important in signal transduction. STZ-induced diabetes (an animal model for insulin-dependent diabetes mellitus, IDDM) resulted in a 2-fold increase in rat liver NMT activity as compared with control animals. In obese Zucker (fa/fa) rats (an animal model for non-insulin dependent diabetes mellitus, NIDDM) there was a∼4.7-fold lower liver particulate NMT activity as compared with the control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalised liver NMT activity. These results would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation.
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    URL: http://dx.doi.org/10.1007/BF01075931
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    Heat shock protein 72 in cardiac and skeletal muscles during hypertension (1995)
    Springer
    Molecular and cellular biochemistry 146 (1995), S. 1-6 
    Details
    ISSN: 1573-4919
    Keywords: heat shock protein ; hypertension ; aging ; myocardium ; skeletal muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In order to elucidate the relationship between hypertension and hypertrophy in the production of heat shock proteins, we studied the induction of the HSP72 synthesis by the heart and gracilis muscles of normo (WKY) and hypertensive (SHR) rats subjected to hyperthermia (42°C±0.5 for 15 min). Two age groups were investigated in each strain: young (2 months, with developing cardiac hypertrophy) and old (18 months, with fully developed chronic cardiac hypertrophy). The gracilis muscle never developed hypertrophy, independently of hypertension or aging. 72 kDa inducible protein was determined by Western blot analysis using a specific monoclonal antibody. We also used a commercial standard, loaded on each blot, to quantitate densitometrically the signal. The heart of young SHR responds to heat shock more than their normotensive age-matched control (298.8±24.7% vs 88.3 ±8.5%, p〈0.001). This response is not maintained during aging as we did not find any significant difference between normo-and hypertensive old rats after exposure to hyperthermia (43.6±5.3% vs 65.3±10.4%). Unlike the heart, the gracilis muscle shows a basal spontaneous HSP72 synthesis in both the SHR (71.4±10.8%) and WKY (40.6±11.7%) animals. There was a significant increase in HSP72 synthesis in the gracilis muscle of young SHR with respect to their control (186.2±18.7% vs 115.8±9.9%, p〈0.02) which was maintained also during aging (171.9±17.3% vs 95.2±10.5%, p〈0.01). In conclusion, these data show that hypertension results in an increased synthesis of HSP72 both in cardiac and gracilis muscle in response to heat shock. This abnormal response is attenuated by aging in the heart but not in the gracilis muscle. Thus, the abnormality seems to be independent from hypertrophy and linked to genetic determination of the disease.
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    Effect of cadmium, mercury and copper on partially purified hepatic flavokinase of rat (1997)
    Springer
    Molecular and cellular biochemistry 167 (1997), S. 73-80 
    Details
    ISSN: 1573-4919
    Keywords: cadmium ; zinc ; liver ; flavokinase ; thiol group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of cadmium (Cd2+), mercury (Hg2+) and copper (Cu2+) was studied with partially purified flavokinase (ATP:riboflavin 5′-phosphotransferase EC 2.7.1.26) from rat liver. All the divalent heavy metal cations inhibited flavokinase activity in a concentration-dependent manner. The inhibitory effect of cadmium on the enzyme was completely reversed by increasing concentration, of Zinc (Zn2+) indicating a competition between Zn2+ and Cd2+ for binding with the enzyme. A competition between riboflavin and Cd2+ is also evident from the present investigation. These observations hint at the possibility that Zn2+ and Cd2+ probably compete for the same site on the enzyme where riboflavin binds. However, inhibition of flavokinase by Hg2+ could not be reversed by Zn2+. Our studies further reveal that hepatic flavokinase appears to contain an essential, accessible and functional thiol group(s) which is evident from a concentration dependent inhibition of activity by sulfhydryl reagent s like parachloromercuribenzoate (PCMB), 5,5′-dithiobis (2-nitrobenzoic acid)(DTNB), and N-ethylmaleimide (NEM). Inhibition of flavokinase by sulfhydryl reagents were protected, except in case of NEM inhibition, when the enzyme was incubated with thiol protectors like glutathione (GSH) and dithiothreitol (DTT). Furthermore, the enzyme could also be protected from the inhibitory effect of Cd2+ and Hg2+ by GSH and DTT suggesting that Cd2+ probably interacts with a reactive thiol group at or near the active site of enzyme in bringing about its inhibitory effect. (Mol Cell Biochem 167: 73-80, 1997)
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    URL: http://dx.doi.org/10.1023/A:1006815504302
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    Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion (1997)
    Springer
    Molecular and cellular biochemistry 176 (1997), S. 337-347 
    Details
    ISSN: 1573-4919
    Keywords: antioxidant enzymes ; sub-cellular organelles ; liver ; ischemia-reperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The activities of rat hepatic subcellular antioxidant enzymes were studied during hepatic ischemia/reperfusion. Ischemia was induced for 30 min (reversible ischemia) or 60 min (irreversible ischemia). Ischemia was followed by 2 or 24 h of reperfusion. Hepatocyte peroxisomal catalase enzyme activity decreased during 60 min of ischemia and declined further during reperfusion. Peroxisomes of normal density (d = 1.225 gram/ml) were observed in control tissues. However, 60 min of ischemia also produced a second peak of catalase specific activity in subcellular fractions corresponding to newly formed low density immature peroxisomes (d = 1.12 gram/ml). The second peak was also detectable after 30 min of ischemia followed by reperfusion for 2 or 24 h. Mitochondrial and microsomal fractions responded differently. MnSOD activity in mitochondria and microsomal fractions increased significantly (p 〈 0.05) after 30 min of ischemia, but decreased below control values following 60 min of ischemia and remained lower during reperfusion at 2 and 24 h in both organelle fractions. Conversely, mitochondrial and microsomal glutathione peroxidase (GPx) activity increased significantly (p 〈 0.001) after 60 min of ischemia and was sustained during 24 h of reperfusion. In the cytosolic fraction, a significant increase in CuZnSOD activity was noted following reperfusion in animals subjected to 30 min of ischemia, but 60 min of ischemia and 24 h of reperfusion resulted in decreased CuZnSOD activity. These studies suggest that the antioxidant enzymes of various subcellular compartments respond to ischemia/reperfusion in an organelle or compartment specific manner and that the regulation of antioxidant enzyme activity in peroxisomes may differ from that in mitochondria and microsomes. The compartmentalized changes in hepatic antioxidant enzyme activity may be crucial determinant of cell survival and function during ischemia/reperfusion. Finally, a progressive decline in the level of hepatic reduced glutathione (GSH) and concomitant increase in serum glutamate pyruvate transaminase (SGPT) activity also suggest that greater tissue damage and impairment of intracellular antioxidant activity occur with longer ischemia periods, and during reperfusion.
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    Tyrosine aminotransferase deficiency in mink (Mustela vision): A model for human tyrosinemia II (1981)
    Springer
    Biochemical genetics 19 (1981), S. 687-693 
    Details
    ISSN: 1573-4927
    Keywords: mink ; tyrosine aminotransferase ; liver ; tyrosinemia II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Mink pseudodistemper, a recessive disease associated with high blood tyrosinelevels, is an animal analogue of the human inborn error of metabolism, tyrosinemia II. Affected mink and man have eye and skin lesions. Affected mink have no hepatic tyrosine aminotransferase (TAT) activity, as measured immunologically and biochemically. Hepatic mitochondrial aspartate aminotransferase is increased to 188% of control. This new genetic animal model of TAT deficiency should allow new studies of tyrosine metabolism.
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    URL: http://dx.doi.org/10.1007/BF00484001
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    Increased potency of vanadium using organic ligands (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 175-180 
    Details
    ISSN: 1573-4919
    Keywords: Vanadium ; diabetes ; insulin-mimetic ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Thein vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed. We have synthesized several organic vanadium compounds and one compound, bis(maltolato)oxovanadium(IV) or BMOV, has been extensively investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic rats when administered in drinking water over a 25 week period. The maintenance dose (0.18 mmol/kg/day) was approximately 50% of that required for vanadyl sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also reduced blood glucose levels. The ED50 for BMOV was 0.5 mmol/kg, while for VS the estimated ED50 was 0.9 mmol/kg. BMOV was also effective by the intraperitoneal route in STZ-diabetic rats. The ED50 was 0.08 mmol/kg compared to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min period reduced plasma glucose levels by 50% while VS was not effective.
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    Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: Purification and kinetic characterization (1997)
    Springer
    Molecular and cellular biochemistry 166 (1997), S. 55-63 
    Details
    ISSN: 1573-4919
    Keywords: cadmium ; glutathione S-transferase ; liver ; kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Exposure of animals to cadmium (Cd) (25 mg kg-1 body wt day-1) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IFP) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. α, µ and π, which were serologically identical to human α, µ and π GSTs. (Mol Cell Biochem 166: 55-63, 1997)
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    Antihypertensive effects of vanadium compounds in hyperinsulinemic, hypertensive rats (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 205-209 
    Details
    ISSN: 1573-4919
    Keywords: hyperinsulinemia ; insulin resistance ; hypertension ; vanadium compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Although considerable evidence lends credence to the association between insulin resistance, hyperinsulinemia and essential hypertension, the precise nature of this relationship remains unexplained. In the present investigation, we examined the proposition that these metabolic defects contribute causally to the development of high blood pressure. If these metabolic abnormalities were responsible for the development of hypertension, then drug interventions that improve these defects should also decrease high blood pressure. Since previous studies have demonstrated that vanadium compounds enhance insulin action and lower plasma insulin levels in nondiabetic rats, we examined the effects of these compounds on insulin sensitivity, plasma insulin concentration and blood pressure in two hyperinsulinemic models of experimental hypertension. The animal models studied were the genetically predisposed spontaneously hypertensive rat and the fructose-hypertensive rat, where hypertension is induced in normotensive rats by feeding them a high fructose diet. Vanadium compounds caused marked and sustained decreases in plasma insulin concentration and blood pressure in both the animal models studied. Furthermore, the effect of the drugs on blood pressure was reversed by restoring plasma insulin levels in the drug-treated rats to those observed in their untreated counterparts. These data suggest that either hyperinsulinemia contributes to the development of hypertension in both the spontaneously hypertensive and the fructose-hypertensive rats or that the underlying mechanism is closely related to the expression of both these disorders.
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    URL: http://dx.doi.org/10.1007/BF01075939
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    In vivo effects of vanadate on hepatic glycogen metabolizing and lipogenic enzymes in insulin-dependent and insulin-resistant diabetic animals (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 87-94 
    Details
    ISSN: 1573-4919
    Keywords: vanadate ; diabetes ; glycogen synthase ; phosphorylase ; lipogenic enzymes ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The insulin-mimetic action of vanadate is well established but the exact mechanism by which it exerts this effect is still not clearly understood. The role of insulin in the regulation of hepatic glycogen metabolizing and lipogenic enzymes is well known. In our study, we have, therefore, examined the effects of vanadate on these hepatic enzymes using four different models of diabetic and insulin-resistant animals. Vanadate normalized the blood glucose levels in all animal models. In streptozotocin-induced diabetic rats, the amount of liver glycogen and the activities of the active-form of glycogen synthase, both active and inactive-forms of phosphorylase, and lipogenic enzymes like glucose 6-phosphate dehydrogenase and malic enzyme were decreased and vanadate treatment normalized all of these to near normal levels. The other three animal models (db/db mouse, sucrose-fed rats and fa/fa obese Zucker rats) were characterized by hyperinsulinemia, hypertriglyceridemia, increases in activities of lipogenic enzymes, and marginal changes in glycogen metabolizing enzymes. Vanadate treatment brought all of these values towards normal levels. It should be noted that vanadate shows differential effects in the modulation of lipogenic enzymes activities in type I and type II diabetic animals. It increases the activities of lipogenic enzymes in streptozotocin-induced diabetic animals and prevents the elevation of activities of these enzymes in hyperinsulinemic animals. The insulin-stimulated phosphorylation of insulin receptor β subunit and its tyrosine kinase activity was increased in streptozotocin-induced diabetic rats after treatment with vanadate. Our results support the view that insulin receptor is one of the sites involved in the insulin-mimetic actions of vanadate.
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    URL: http://dx.doi.org/10.1007/BF01075922
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