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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urinary kallikrein excretion was significantly lower in patients with essential hypertension (0.48±0.05 EU/24 h) than in normotesive controls (1.26±0.14 EU/24 h).Oral administration of hog pancreatic kallikrein normalized decreased urinary kallikrein and reduced arterial pressure.The treatment-induced rise in uriary kallikrei was due to an enhanced release of endogenous enzyme, as was determined by radioimmunoassay. It is proposed that in the hypertensive patients the low urinary kallikrein excretion reflects a defect in renal kallikrein formation which is normalized by oral kallikrein. The hypotensive action of oral kallikrei, as well as its stimulating effects on renal kallikrein release, suggest that the kallikrein-kinin system is involved in blood pressure regulation and that imparied renal kallikrein activity may be a factor in the maintenance of essential hypertension.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 44 (1966), S. 1355-1360 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Concluding from observations during water diuresis and osmotic diuresis it has been suggested that the application of saluretics may cause a disturbance of osmotic regulation. Since neither form of experimental diuresis corresponds to the fluid retention in pathological states, the effects of a single intravenous injection of 25 mg Furosemide on the free water clearance were studied under clearance conditions in both normal persons and patients with impaired renal function. It was demonstrated that the application of the saluretic during saline infusion always causes a slight increase of the urinary osmotic concentration: In normal persons the maximal fluid excretion after the injection of 25 mg Furosemide averaged 21.3% of the filtered volume, whereas the osmotic clearance increased to 23.6% of the glomerular filtrate. The respective values obtained in patients with impaired renal function were 19.87% for the volumen and 29.45% for the osmotic clearance. Possible errors in applying principles of water and osmotic diuresis in pharmacological studies of diuresis are discussed. The results also permit a conclusion on the site of action of Furosemide in the nephron.
    Notes: Zusammenfassung Aus Beobachtungen während Wasser- und osmotischer Diurese wird häufig der Schluß gezogen, daß bei Verabreichung von Saluretika Störungen der osmotischen Regulation zustande kommen können. Da beide Diureseformen jedoch Eigenwirkungen entfalten und außerdem häufig nicht der klinischen Situation einer pathologischen Flüssigkeitsretention entsprechen, wurden in der vorliegenden Arbeit die Auswirkungen einer einmaligen i.v.-Injektion von 25 mg Furosemid unter Clearancebedingungen während einer Infusion mit 0,9% iger NaCl-Lösung bei gesunden Versuchspersonen und Patienten mit eingeschränkter Nierenfunktion untersucht. Dabei konnte nachgewiesen werden, daß unter den gewählten Versuchsbedingungen durch die Wirkung des Saluretikum unabhängig von der Ausgangslage immer ein leichter Konzentrationseffekt des Urins hervorgerufen wird: Bei Gesunden werden nach Furosemidgabe im Mittel maximal 21,3% der filtrierten Flüssigkeit ausgeschieden, während der prozentuale Anteil der osmotischen Clearance an der Filtrationsrate auf 23,6% gesteigert wird. Bei Patienten mit eingeschränkter Nierenfunktion kommt es unter den gleichen Bedingungen unter Furosemid zum Anstieg des Harnzeitvolumens auf 19,87% und der osmotischen Clearance auf 29,45% der glomerulären Filtrationsrate. Die Fehlermöglichkeiten einer Versuchsanordnung mit Wasser- und osmotischer Diurese werden diskutiert. Die Ergebnisse lassen gleichzeitig einen Schluß auf die Angriffspunkte des Saluretikum Furosemid im Nephron zu.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 49 (1971), S. 1147-1148 
    ISSN: 1432-1440
    Keywords: ADH-bioassay ; pathogenesis of edema ; ADH-Bioassay ; ödempathogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Durch simultane Registrierung von Urinvolumenänderungen und elektrischer Leitfähigkeit konnte der biologische ADH-Nachweis an der hydrierten Ratte in Alkoholnarkose bei Steigerung der Empfindlichkeit verbessert werden. An gesunden Normalpersonen wurden damit durchschnittliche Plasma-ADH-Konzentrationen um 3,5 εE/ml bestimmt. Weitere Untersuchungen sind auf die Bedeutung des Hormons bei der ödempathogenese gerichtet.
    Notes: Summary By simultaneous recording of urine volume and conductivity the method of ADH determination could be improved and increased sensitivity was obtained. The mean plasma concentrations in normally hydrated healthy subjects were found to be 3.5 εU/ml. The method is used to investigate the importance of ADH in edematous states.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 49 (1971), S. 1267-1271 
    ISSN: 1432-1440
    Keywords: non diabetic hyperinsulinism ; Kimmelstiel-Wilson's glomerulosclerosis ; Diabetes mellitus ; Glomerulosklerose ; Kimmelstiel-Wilson ; Glomerulonephritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird über den Krankheitsverlauf einer chronischen Glomerulonephritis mit nephrotischer Verlaufsform und schwerer Hypertonie berichtet, die histologisch die typischen Veränderungen einer intercapillären Glomerulosklerose Kimmelstiel-Wilson aufzeigte. Eine Glucosetoleranzstörung war bei dem Patienten mit Sicherheit ausgeschlossen. Es bestanden jedoch deutlich erhöhte Insulin-Konzentrationen. Dabei wird festgestellt, daß die für die Glomerulosklerose Kimmelstiel-Wilson als charakteristisch angesehenen Veränderungen auch ohne manifeste diabetische Stoffwechselstörung auftreten können. Es muß abgeklärt werden, ob dabei dem Insulin eine besondere Rolle zukommt oder ob es sich um unspezifische histologische Veränderungen handelt.
    Notes: Summary In a patient suffering of chronic glomerulonephritis with malignant hypertension, necropsy revealed histological changes considered to be typical for Kimmelstiel-Wilson's glomerulosclerosis. A disturbance of carbohydrate metabolism had been clearly excluded. However, the patient showed uremic hyperinsulinism. The findings suggest that histological changes regarded as typical for Kimmelstiel-Wilson's glomerulosclerosis may as well be found without any disturbances of carbohydrate metabolism. Experimental and clinical data suggest that insulin may be of special importance in the development of hyaline masses as seen in “diabetic glomerulosclerosis”.
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  • 5
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 20 normo- und hypertensiven Patienten mit normaler und verschieden stark eingeschränkter Nierenfunktion wurde das Verhalten der renalen Hämodynamik unter intravenöser Gabe von Etacrynsäure (50 mg initial mit anschließender Dauerinfusion von 50 mg/Std) im akuten Experiment unter Clearance-Bedingungen geprüft. Eine eindeutige Änderung der glomerulären Filtrationsrate (GFR) wurde dann angenommen, wenn die Abweichung von den Kontrollen, deren Schwankungsbreite ± 10% nicht überschreiten durfte, wiederholt mehr als 10% betrug. Von 19 Probanden zeigten 7 (Gruppe A) einen kontinuierlichen Abfall und 8 (Gruppe B) einen Anstieg der GFR, der allerdings auf die ersten 30–45 min beschränkt war. Dieser Unterschied zwischen beiden Gruppen ist bei doppelter Varianzanalyse fürα〈0,001 zu sichern. Der effektive renale Plasmastrom (RPF) verhielt sich nur zum Teil gleichsinnig. Die Filtrationsfraktion hatte bei Gruppe A eine leicht sinkende (α〈0,05), bei Gruppe B eine steigende Tendenz. Bei der Analyse der Ursachen dieses divergierenden Verhaltens der renalen Hämodynamik konnte ein methodischer Fehler im Sinn eines „Auswascheffektes“ ausgeschlossen werden: Das Maximum der glomerulären Filtrationsrate wurde in Gruppe B durchschnittlich erst nach 45 min erreicht. Bei Gruppe A kam in der gleichen Zeit ein Abfall zustande. Die Ausgangswerte der glomerulären Filtrationstrate lagen bei beiden Gruppen in gleicher Größenordnung. Dagegen waren Harnzeitvolumen und renale Natriumausscheidung in Gruppe A vor und in den beiden ersten Clearanceperioden nach Etacrynsäure-Gabe signifikant höher als in Gruppe B (α bis〈0,01). Diese Unterschiede kamen auch in der fraktionalen Natriumausscheidung, der tubulären Reabsorptionsfraktion von Natrium sowie der osmolalen Clearance zum Ausdruck. Sie beruhen wahrscheinlich in erster Linie darauf, daß es sich bei Gruppe A ausschließlich um Personen mit Blutdrucksteigerung handelt, deren Neigung zu beschleunigter Natrium-Elimination bekannt ist, während Gruppe B fast nur normotensive Probanden umfaßt. Das Absinken der GFR in Gruppe A erklärt sich somit am ehesten mit einer frühzeitig einsetzenden, kumulativ negativen Natrium- und Wasserbilanz mit konsekutiver Hypovolämie, die am Verhalten des peripheren Blutdrucks allerdings nicht nachweisbar war. Bei den Probanden der Gruppe B kommt diese bilanzmäßig bedingte Kontraktion des Extracellulärraums erst nach 45 min zur Auswirkung, so daß die Reaktion der renalen Hämodynamik initial von der durch Etacrynsäure an sich verursachten Dilatation der Nierengefäße geprägt wird. Die vorliegenden Ergebnisse geben jedoch keinen weiteren Aufschluß über die pharmakologischen Grundlagen dieser renalen Mehrdurchblutung.
    Notes: Summary Changes of renal hemodynamics after intravenous application of ethacrynic acid (50 mg prime injection followed by an infusion of 50 mg/h) were investigated during acute clearance conditions in 20 subjects with normal and elevated blood pressure and various degrees of impaired renal function. The change of glomerular filtration rate was only accounted as definitive when the deviation from the controls was more than 10% in different clearance periods. In 7 of 19 experiments, ethacrynic acid caused a decrease of glomerular filtration rate (group A), whereas 8 experiments showed an increase (group B) which, however, was limited to the first 30–45 min. The difference between both groups proved to be statistically significant at double variance analysis (α〈0.001). The effective renal plasma flow was only partially modified in the same direction. The filtration fraction was decreasing in group A (α〈0.05) and slightly increasing in group B. In analyzing the causes of these different effects of ethacrynic acid on renal hemodynamics, a “washout effect” could be excluded: The maximum rise of glomerular filtration rate in group B was only reached after 45 min. In contrast, the decrease in group A developed within the same time interval. In the control periods glomerular filtration rate in both groups remained within the same order of magnitude. On the other hand, urine volume and renal sodium excretion in group A (decreasing filtration rate) exceeded that of group B not only initially but also during the first two clearance periods after ethacrynic acid administration. These differences were also observed in fractional renal sodium excretion, tubular sodium reabsorption, and osmolar clearance. They are most probably the consequence of the increased arterial pressure of all patients in group A, since the tendency to exaggerated sodium elimination of hypertensive patients is well known. All subjects of group B were normotensive. The declining glomerular filtration rate in group A can best be explained by an early onset of cumulative negative sodium balance with consecutive hypovolemia which does however not affect the peripheral blood pressure. In group B, the contraction of extracellular fluid volume did not occur until 45 min after the application of ethacrynic acid. Thus, the reaction of renal hemodynamics in this group is initially influenced by the dilatation of the renal vessels caused by the drug. A further explanation of the pharmacological basis of this increase in renal blood perfusion, however, cannot be given by the experiments reported.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 61 (1983), S. 311-319 
    ISSN: 1432-1440
    Keywords: Bartter's syndrome ; Tubular function ; Hypokalemia ; Prostaglandins ; Renin-angiotensin-aldosterone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies have demonstrated that patients with Bartter's syndrome regularly exhibit a reduced tubular absorption of chloride in the ascending limb of Henle. This defect represents the most ‘proximate’ abnormality of the syndrome so far identified. It causes renal potassium loss through reduced potassium cotransport in the ascending limb of Henle as well as through increased tubular flow rate stimulating potassium secretion in the distal nephron. Hypokalemia per se may stimulate renal and vascular prostaglandin synthesis. Prostaglandins in turn mediate the increased activity of the renin-angiotensin-aldosterone system and may also participate in the vascular resistance to the pressor action of exogenous angiotensin II and norepinephrine. The differential diagnosis of Bartter's syndrome includes syndromes with hypokalemic alkalosis and a stimulated renin-angiotensin-aldosterone system such as extrarenal electrolyte losses and diuretic abuse. Extrarenal electrolyte loss can be identified through metabolic studies with determination of urinary electrolyte excretion and by the determination of the fractional free-water clearance during sustained water diuresis. Covert diuretic abuse may be identified through a screen of the urine for the presence of diuretics and by marked day-to-day variations in urinary electrolyte excretion during metabolic studies. The therapcutic approach to Bartter's syndrome includes administration of potassium chloride and potassium-sparing diuretics as well as of inhibitors of prostaglandin synthesis.
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  • 7
    ISSN: 1432-1440
    Keywords: Na-K-ATPase ; Ouabain ; Natriuretic hormone ; Intracellular electrolytes ; Peripheral vascular resistance ; Cardiac function ; Hypertension ; Calcium entry blockade ; Human studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 µg ouabain/kg body weight inhibited red blood cell (RBC) — Na-K-ATPase by 49% which was accompanied by a significant increase in RBC — ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vaso-constriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase — in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion — may play a role in the pathogenesis of human arterial hypertension.
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  • 8
    ISSN: 1432-1440
    Keywords: Potassium intake ; Sodium intake ; Natriuresis ; Essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hemodynamic, hormonal, and renal responses to alterations in dietary potassium were studied in normotensive and hypertensive subjects. In a short-term study, nine normotensive and nine hypertensive young men received a normal diet and low potassium, high potassium, and high potassium/low sodium diets for 1 week, each. The long-term effect of potassium supplementation (normal diet plus 96 mmol KCl/d for 8 weeks) was evaluated in 17 patients with essential hypertension. Blood pressure did not change significantly during short-term alterations of potassium intake but decreased during long-term supplementation (from 152.2±3.5/99.6±1.9 mm Hg to 137.4±2.9/89.1±1.4 mm Hg). High dietary potassium induced a significant but transient natriuresis. Plasma potassium concentration was increased during long- but not during short-term high potassium intake. In contrast to plasma renin activity (PRA) and aldosterone, urinary kallikrein was consistently stimulated during long-term potassium supplementation. The plasma concentrations of adrenaline and noradrenaline were significantly higher in hypertensive than in normotensive subjects and were not markedly altered by the dietary changes. It is concluded that long- but not short-term potassium supplementation lowers blood pressure in patients with essential hypertension. The antihypertensive effect may be mediated by potassium-induced natriuresis, by a stimulation of Na-K-ATPase secondary to increased plasma potassium levels, and/or by a modulation of the renin-angiotensin-aldosterone, kallikrein-kinin, and sympathetic nervous systems.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 44 (1966), S. 1349-1355 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The influence of a repeated oral fluid loading on renal sodium excretion was analysed in 12 normal persons and 14 patients with hypertensive disease of various origin. In normal persons, the oral hydration produced a continuous increase of renal sodium excretion, whereas urine volume, endogenous creatinine clearance and tubular sodium load remained essentially unchanged. In hypertensive patients, a maximal natriuresis occurred in the first hour after hydration and was followed by a decrease of sodium excretion together with a reduction of endogenous creatinine clearance and tubular sodium load. As the cause of the increasing sodium excretion in normal persons after oral hydration an endogenous natriuretic principle is postulated, acting mainly on the sites of anisotonic sodium transport. The mechanism of the initial hypernatriuresis in patients with hypertensive disease after oral hydration is still not completely understood. It is concluded that the effect of hydration on sodium diuresis in normals is different from that in hypertensive patients.
    Notes: Zusammenfassung An 12 gesunden Versuchspersonen und 14 Patienten mit Hochdruckerkrankung verschiedener Genese wird der Einfluß einer wiederholten oralen Flüssigkeitsbelastung auf die renale Natrium-Ausscheidung untersucht. Bei Gesunden kommt durch die Flüssigkeitsgabe ein stetiger Anstieg der Natrium-Ausscheidung zustande, während Harnzeitvolumen, Clearance des endogenen Kreatinin und tubuläres Natrium-Angebot im Mittel unverändert bleiben. Bei Hochdruckpatienten findet sich bereits in der ersten Stunde nach der Flüssigkeitsgabe eine maximale Natriurese, die jedoch im weiteren Verlauf des Versuches in Korrelation zur Clearance des endogenen Kreatinin und zum tubulären Natrium-Angebot zurückgeht. Als Ursache der zunehmenden Natrium-Ausscheidung bei gesunden, normotensiven Versuchspersonen wird ein endogener natriuretischer Mechanismus postuliert, der vorwiegend an den Stellen des anisotonen Natrium-Transportes wirksam wird. Die Ursache der intitialen Hypernatriurese bei Hochdruckpatienten nach Flüssigkeitsbelastung ist noch nicht völlig geklärt. Es läßt sich jedoch schließen, daß ihr ein anderer Vorgang zugrunde liegt als der durch Flüssigkeitsgabe ausgelösten Natriurese bei Normalpersonen.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 50 (1972), S. 186-190 
    ISSN: 1432-1440
    Keywords: ADH ; heart failure ; oedema ; ADH ; Herzinsuffizienz ; Ödem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Entwicklung einer geeigneten biologischen Untersuchungsmethode für ADH wurden die Plasmakonzentrationen des Hormones bei Gesunden und Patienten mit kardialer Stauungsinsuffizienz untersucht. Dabei wurde festgestellt, daß bei klinisch manifester Herzinsuffizienz deutlich erhöhte Plasma-ADH-Aktivitäten gegenüber einem vergleichbaren Normalkollektiv vorliegen.
    Notes: Summary For ADH determination in man the bioassay of hydrated rats under alcohol anesthesia could essentially be improved. It was so possible to determine reproducibly the ADH concentration in normal hydrated men and patients with heart failure. The data clearly suggest that plasma ADH is elevated in the latter disease in comparison with the group of normal controls.
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