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  • 1
    Electronic Resource
    Electronic Resource
    Lipid lowering treatment with bezafibrate in patients on chronic haemodialysis: Pharmacokinetics and effects (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 910-916 
    Details
    ISSN: 1432-1440
    Keywords: Hyperlipidaemia ; Cholesterol ; Triglycerides ; Uraemia ; Regular haemodialysis treatment ; Bezafibrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperlipidaemia may contribute to the high rate of cardiovascular complications in patients on chronic haemodialysis (CHD). However, possibilities of lipid lowering therapy in CHD are still limited. The applicability of bezafibrate (BF), a recently developed clofibrate analogue, was investigated in patients on CHD with triglyceride and/or total cholesterol levels above 300 mg/dl. The lipid lowering effect was studied in a placebo-controlled trial over 6 months in 19 patients. Long-term effect was followed in six patients over a mean period of 29 months. Elimination half-life and mean therapeutic serum concentration were calculated by 72-h BF serum profiles, obtained after the first drug administration of a single 200-mg dose and during steady state after 12 weeks of treatment. Elimination half-lives were 17 h at start and 22 h after 12 weeks compared with 2 h in subjects with normal renal function. Dose reduction to 200 mg every 3rd day was necessary and resulted in a mean therapeutic serum concentration of 3.4 mg/l, which was similar to 3.0 mg/l of normal subjects, who received the dose optimal for lowering of lipids (200 mg 3 × /day). The protein-bound serum fraction of BF was decreased to 8% in CHD patients, compared with 95% found in normal subjects. BF therapy resulted in a marked reduction of serum triglycerides from 478 mg/dl by 31% and total cholesterol levels from 311 mg/dl by 19% as well as β-Lp-cholesterol from 178 mg/dl by 17%, whereas the initially low α-Lp-cholesterol increased significantly from 18,3 mg/dl by 58%. Under long-term therapy not only continuously low triglyceride and cholesterol levels could be maintained, moreover a further decline (−20% and −7%) could be achieved. Safety laboratory controls, comprising haemoglobin, bilirubin, liver enzymes, CK and albumin, showed no significant changes apart from a slight reversible increase in CK and a decrease in gamma-GT and alkaline phosphatase. Subjective side effects were not reported. Under this dosage schedule, BF therapy was thus effective and safe, improving potentially atherogenic disturbances of lipid metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728614
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  • 2
    Electronic Resource
    Electronic Resource
    Die Rolle des Erythropoietinmangels in der Pathogenese der renalen Anämie (1979)
    Springer
    Journal of molecular medicine 57 (1979), S. 1031-1036 
    Details
    ISSN: 1432-1440
    Keywords: Renal anemia ; Pathogenesis ; Erythropoietin deficiency ; Renale Anämie ; Pathogenese ; Erythropoietinmangel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird eine Übersicht gegeben über klinische Untersuchungen, die mit einem hochsensiblen in-vitro Erythropoietin Assay (foetale Mäuseleberzellkultur) zur Klärung der umstrittenen Rolle des Erythropoietinmangels in der Pathogenese der renalen Anämie an großen Patientenpopulationen durchgeführt wurden. Die Studien betrafen: a.) chronisch Nierenkranke mit variierender Funktionsein-schränkung in der Vordialysephase b.) nicht nephrektomierte und anephrische chronische Dialysepatienten. Die bisher vorliegenden Ergebnisse belegen, daß die Anfangsphase der renalen Anämie mit einem kompensatorischen Anstieg der Serumerythropoietinkonzentration einhergeht und somit ein Erythropoietinmangel nicht die primäre Ursache dieser Anämie sein kann; lediglich ein relativer Erythropoietinmangel ist anzunehmen. Erst in der Terminalphase der Niereninsuffizienz wird der Erythropoietinmangel absolut, so bei 50% der untersuchten chronischen, nichtnephrektomierten Hämodialysepatienten und bei allen anephrischen Patienten. An einzelnen Patienten läßt sich aber selbst in der terminalen Niereninsuffizienz eine Regulierbarkeit der Serumerythropoietinkonzentration über den Hämatokrit im Sinne eines negativen feedback nachweisen, der auf einem subnormalen Hämatokritniveau arbeitet.
    Notes: Summary A review is given of clinical studies performed by use of a highly sensitive in-vitro erythropoietin assay (fetal mouse livercell culture) in large patients' populations to clarify the controversial role of erythropoietin deficiency in the pathogenesis of renal anemia. Studies involved a.) patients with chronic renal disease and varying degree of renal insufficiency in the predialysis phase b.) non-nephrectomized and anephric patients on regular hemodialysis treatment. The data available demonstrate that the initial phase of renal anemia is accompanied by a compensatory increase of serumerythropoietin concentration and therefore erythropoietin deficiency has to be excluded as a primary cause of the anemia of renal failure; merely a relative lack of erythropoietin seems to exist. In the terminal phase of renal failure, erythropoietin deficiency becomes absolute, such in 50% of the investigated non-nephrectomized hemodialysis patients and in all anephric patients. However in individual patients even in terminal renal failure a sustained regulatory feedback mechanism between serume-rythropoietin concentration and hematocrit, probably working at lower hematocrit level, could be demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01479988
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  • 3
    Electronic Resource
    Electronic Resource
    Reflection coefficient and permeability of urea in the proximal convolution of the rat kidney (1972)
    Springer
    The journal of membrane biology 7 (1972), S. 377-390 
    Details
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The transport theory of Kedem and Katchalsky which was derived for passive transport in a two-compartment system is generalized for a multicomponent system with active transport, so that it can be applied to more complicated biological membranes. Equations have been derived to describe the transport of urea through the proximal convolution of the rat kidney and the permeability and the reflection coefficient have been determined. The permeability coefficient $$(\tilde P_u )$$ measured with the microperfusion and stop flow microperfusion methods, was found to be 6.0 and 5.2×10−5 mm2/sec, respectively. The reflection coefficient (σ) was determined in a stationary state situation and found to be 0.68. Earlier free flow micropuncture results together with theP u andσ u of this study indicate that 50% of the filtered urea is reabsorbed proximally and that approximately half of this amount is reabsorbed by solvent drag and the rest by diffusion. In the Appendix, a theoretical treatment of nonelectrolyte transport in a multicomponent system with active transport is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01867927
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacodynamics and pharmacokinetics of three different doses of urapidil infused in hypertensive patients (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 549-552 
    Details
    ISSN: 1432-1041
    Keywords: urapidil ; pharmacodynamics ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33±8 mmHg, the 65 mg dose a maximum decrease of 39±12 mmHg and the 130 mg dose a maximum decrease of 50±12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses. In severe hypertension, the 130 mg dose can be employed, since it does result in a further, significantly larger decrease in blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542413
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  • 5
    Electronic Resource
    Electronic Resource
    The role of bicarbonate and other buffers on isotonic fluid absorption in the proximal convolution of the rat kidney (1971)
    Springer
    Pflügers Archiv 330 (1971), S. 149-161 
    Details
    ISSN: 1432-2013
    Keywords: Proximal Convolution ; Isotonic Reabsorption ; Bicarbonate Buffer ; Lipid Soluble Buffers ; Sodium Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fluid reabsorption from the proximal convolution of the rat kidney was measured with the Gertz shrinking droplet technique. Simultaneously, the peritubular capillaries were perfused with artificial solutions. In some experimental series, fluid from the shrinking droplet was withdrawn and analysed for Cl−, Na+, and osmolality so that the transtubular transport of Na+, Cl−, and HCO 3 − could be calculated. Capillary perfusate in some experiments was also withdrawn and its pH was measured. The following results were obtained: 1. With increasing concentration of HCO 3 − in the capillary perfusate, the transtubular water, sodium, chloride, and bicarbonate reabsorption increased. 2. The sulfonamide buffers sulfamerazine and glycodiazine (Redul®), which easily penetrate the tubular wall, could, in equimolar concentrations, substitute totally for the bicarbonate buffer in promoting isotonic fluid absorption. 3. Butyrate, propionate, and acetate were also effective; pyruvate, lactate, and paraaminohippurate, however, were not. 4. The effect of HCO 3 − and glycodiazine on isotonic absorption was shown to depend exclusively on the concentration of the buffer anion and not on the concentration of undissociated acid or pH. From these data it is suggested that for proximal isotonic absorption of water, sodium, and chloride, the reabsorption of buffer anions via H+ secretion and nonionic diffusion may be essential. The H+ secretion or the buffer anion absorption across the luminal cell wall may secondarily influence the active Na+ transporting mechanism located at the basal cell site either by a luminal H+−Na+ exchange mechanism or by a lyotropic effect which would increase the Na+ permeability of the luminal cell site. Thereby more Na+ would be delivered to the Na+ pumping site and the rate of Na+ pumping would be augmented.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00643031
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  • 6
    Electronic Resource
    Electronic Resource
    Influence of luminal diameter and flow velocity on the isotonic fluid absorption and36Cl permeability of the proximal convolution of the rat kidney (1971)
    Springer
    Pflügers Archiv 324 (1971), S. 288-296 
    Details
    ISSN: 1432-2013
    Keywords: Renal Microperfusion ; Isotonic Reabsorption ; Tracer Permeability ; Glomerulo Tubular Balance ; Renale Mikroperfusion ; Isotone Resorption ; Tracerpermeabilität ; Glomerulotubuläre Balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the first experimental series proximal convolutions of the rat kidney were perfused with a modified Ringer solution and the isotonic fluid absorption was measured. In a second series the tubule was perfused with equilibrium solution which contained36Cl and the chloride permeability was determined. By the recollection method each individual tubule was perfused twice either at constant luminal diameter but different perfusion rates (10:30 or 6:16 nl/min) or at constant perfusion rates but different luminal diameters (20:30 μ). The perfusate was recollected at two different sites which were at least 500 μ distant from the infusion site. The isotonic fluid absorption as well as the36Cl permeability was unchanged when the tubule was distended from 20–30 μ. Both, however, increased about 20% when the perfusion rate was increased 3-fold. The data led to the following conclusions: 1. It is unlikely that there is a flow reactor type dependence of proximal tubular transport on flow rate. 2. The tubular distension cannot be responsible for the glomerulo-tubular balance. 3. It is more advantageous to relate permeability data of the rat nephron to tubular length. 4. In microperfusion experiments non steady sampling does not affect transepithelial fluxes per unit tubular length, provided that the pump delivery is constant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00592457
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