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C Fleck

Publications and source records attributed to C Fleck.

87 records · Page 5Linked to original sources

[Dose- and age-dependence of the renal tubular transport of p-aminohippuric acid (PAH) in rats after injection of single doses].

The renal excretory capacity for tubularly eliminated foreign substances can be determined with certainty by measuring the excretion of p-aminohippuric acid (PAH). To make superfluous the laborious estimation of the maximum tubular transport capacity in the framework of screening programs, the authors established those doses of PAH the single application of which permits to assess the renal tubular transport capacity of rats of differing ages. Because of its selective renal excretion, it is possible to calculate for PAH a half-time value in urine (t1/2, urine) such as commonly indicated for the serum. Except for extremely high dosages (500 mg PAH/100 g body mass: intraperitoneally), the t1/2, urine value for PAH in adult rats is independent of the dose applied. The t1/2, urine value increases in rats 5 and 10 d of age with increasing PAH doses. In rats of all age-groups, the glomerularly filtered PAH proportion increases with increasing dosage (kinetics in decreasing blood level). In rats 5 and 10 d of age, the proportion of glomerularly filtered PAH in the total amount of excreted PAH is greater than in older rats.

Aging↗

Failure of physostigmine in intoxications with tricyclic antidepressants in rats.

In experiments on rats there is a moderate antagonistic effect of physostigmine against intoxications with the tricyclic antidepressants (TAD) clomipramine, desipramine and imipramine, respectively. During the first hours after TAD intoxication the survival rate is higher in physostigmine treated rats. Especially after relatively low doses of TAD the lethality seems to be reduced by physostigmine treatment. However, at the end of the observation period (96 h) the lethality after TAD is equal with and without physostigmine treatment. The effectivity of physostigmine does not depend on the mode of administration: repeated administration and intravenous infusion are not more effective than a single injection of physostigmine. The influence of TAD on heart rate and respiratory rate was not abolished by physostigmine salicylate. Intoxications with high doses of physostigmine were antagonized by atropine; on the other hand there are no signs for an antagonistic effect of desipramine against physostigmine intoxication, that means their anticipated anticholinergic properties could not be proved.

Animals↗

Urinary enzyme excretion as a indicator of nephrotoxicity in dependence on age.

It was tested whether or not the measurement of urinary enzyme excretion is suitable for detection of nephrotoxic effects in newborn and in old aged rats in the same way as in adult rats. In rats of different ages the renal excretion of lactate dehydrogenase (LDH), leucine aminopeptidase (LAP) and alkaline phosphatase (alP) was measured after administration of a single nephrotoxic dose of uranyl nitrate (0.6 mg/100 g b.wt.). In adult and old aged rats the three enzymes indicate the nephrotoxic effect reliably. In 15- and 20-day-old rats only the alkaline phosphatase seems to be an indicator for the nephrotoxicity of uranyl nitrate. There are differences in the time course of enzymuria in dependence on age.

Aging↗

Stimulation of renal excretion of p-aminohippurate (PAH) after unilateral nephrectomy in adult and ageing rats.

Unilateral nephrectomy (UNX) is followed by a significant decrease of excreted amount of PAH in rats. In 105 and 240-day-old rats, we characterized the time course of restitution of the PAH transport process., Furthermore, we studied whether or not the regeneration of kidney function can be accelerated by repeated administration of cyclopenthiazide. After stimulation of tubular transport of PAH by repeated administration of cyclopenthiazide, the loss of one kidney after UNX can be compensated more rapidly as in nephrectomized rats without pretreatment. In 105-day-old rats the regeneration and the extent of stimulation are more marked than in 240-day-old rats.

Aging↗

Renal blood flow after stimulation of p-aminohippurate transport.

Repeated administration of cyclopenthiazide enhances renal PAH excretion in rats. In the 1st hr after an acute PAH load the renal excretion of PAH is doubled compared with controls. Haemodynamic measurements show that this acute PAH load is related to an increase in renal blood flow, in particular to a distinct increase in blood flow in the renal cortex. This increase in renal blood flow and in intrarenal blood distribution is higher than in stimulated rats. The increase in renal excretion of PAH is stimulated rats is not connected with an increase in renal blood flow. After an acute PAH load an additional increase in renal blood flow in stimulated rats could not be observed as compared with non stimulated control rats.

Aminohippuric Acids↗

[Stimulation of the renal transport of foreign substances following unilateral nephrectomy].

During the phase of compensation of parenchyma loss two different mechanisms can be stated causing an improvement of renal tubular transport capacity. Besides an increase of tubular transport ratio in kidney slices from nephrectomized rats an increased mass of kidney tissue participated in the augmented transport capacity. 24 h after unilateral nephrectomy TmPAH is elevated from 0.40 +/- 0.10 to 0.61 +/- 0.13 mg/min x g kidney weight. The simultaneous increase in slice-to-medium ratio of renal cortical slices demonstrate the increase in specific transport capacity of regenerating kidney tissue. Furthermore the increase in kidney mass is the reason for an elevated transport capacity. Stimulation of renal PAH excretion by repeated pretreatment with cyclopenthiazide shortened the phase of compensation and raised the extent of tubular transport capacity following partial loss of kidney tissue. The specific accumulation of PAH in renal cortical slices from nephrectomized, cyclopenthiazide pretreated rats is distinctly elevated 96 h after unilateral nephrectomy from 19.4 +/- 2.7 to 24.3 +/- 0.6 micrograms/g kidney weight. Obviously there are different mechanisms for the increased PAH transport caused by stimulation and by regeneration after unilateral nephrectomy, because additional effects can be stated in regenerating rats by additional stimulation of renal tubular transport.

Aminohippuric Acids↗

Stimulation of kidney function in rats injured by nephrotoxic agents.

After single administration of potassium dichromate or glycerol, renal PAH excretion was markedly reduced in adult, but not in newborn and infant rats. As already demonstrated in rats with intact kidney functions, repeated administration of PAH or cyclopenthiazide stimulates also renal PAH excretion in rats with acute renal failure. In detail, after PAH or cyclopenthiazide treatment of rats the duration of injury is shortened whereas the intensity of the nephrotoxic effects is not changed. However, the stimulation depends on the age of animals as well as on the nephrotoxic agent administered.

Aging↗

Stimulation of kidney function in rats of different ages injured by nephrotoxic agents.

Intensity and duration of nephrotoxic effects can be characterized by measurement of renal p-aminohippurate (PAH) excretion. Single administration of potassium dichromate or glycerol is followed by a marked decrease of renal PAH excretion in dependence on the time after the administration as well as on the dosage used. Both agents are without effect in young rats with an immature tubular transport system for organic anions. As observed previously in rats with intact kidney function, renal PAH excretion can also be stimulated in rats with potassium dichromate or glycerol induced kidney damage. Stimulation of renal PAH excretion is possible in injured rats by repeated administrations of PAH and cyclopenthiazide, respectively. Exactly, the duration of injury is shortened whereas the intensity of the nephrotoxic effect is not changed. However, this effect depends on the age of rats as well as on the nephrotoxic agent administered.

Aging↗

Ontogenetic aspects of thallium-induced nephrotoxicity in rats.

The effect of Tl2SO4 (Tl, 20 mg kg-1 body wt.) on renal function was investigated in 10- and 20-day-old rats. Nephrotoxic effects were evaluated by the determination of glomerular filtration rate, urinary volume, electrolyte and protein excretion, as well as by morphological investigations. In contrast to adult rats there were no morphological destructions in 10- and 20-day-old rats. Changes in renal function seemed to be less expressed in 10- and 20-day-old than in adult rats. The smaller nephrotoxicity in 10-day-old rats may be caused by lower Tl concentration in renal tissue, whereas in 20-day-old rats decreased nephrotoxicity cannot be explained in this way. The activity of Na+/K(+)-ATPase in rat renal tissues was found to be involved in the mechanisms of Tl enrichment in renal tissue, being an indirect determinant of Tl nephrotoxicity.

Animals↗

Protective effects of methimazole against cisplatin-induced nephrotoxicity in rats.

In adult rats 6 mg kg-1 body wt. cisplatin given i.p. was nephrotoxic. Four days of i.p. treatment with 40 mg kg-1 body wt. methimazole, which started 1 day before CP, prevented increases in blood urea nitrogen and in the renal excretion of proteins. Furthermore, methimazole treatment reduced the oliguric effect of cisplatin and the depression of renal sodium excretion. However, it had no effect on the increased formation of lipid peroxides in cisplatin-damaged kidneys, although repeated treatment with methimazole enhanced the renal glutathione content. Methimazole acts as a radical scavenger, maintaining the glutathione pool in the kidney.

Animals↗

Renal transport of endogenous amino acids. I. Comparison between immature and adult rats.

In the late neonatal period of male Wistar rats (10 days old) concentrations in plasma were higher for 5 of 24 amino acids compared to adult animals (2 months old): beta-alanine, tyrosine, glycine, histidine, and the dipeptide anserine. The plasma concentrations of tryptophan, valine and leucine were lower in young than in adult rats. The renal clearances of amino acids were lower in young rats, both in relation to 1 g b.w. and related to 1 g kidney weight. In the latter case the differences became more distinct because the relative kidney weight was higher in young than in adult animals (1.17 +/- 0.07 vs. 0.82 +/- 0.03 g/100 g b.w.) and significant age differences in renal water content did not exist. The apparently more effective tubular reabsorption capacity in young rats can be explained as follows: Because of the significantly lower GFR in 10-day-old rats compared with adults (0.46 +/- 0.03 vs. 1.10 +/- 0.09 ml/min/1 g kidney), the glomerularly filtered load of amino acids is generally lower in young rats (exceptions: tyrosine, glycine). Therefore, the amino acid transporting carrier systems are able to reabsorb the absolutely lower amounts of amino acids from the ultrafiltrate in immature animals. This hypothesis is supported if one relates the renal amino acid clearance to the clearance of inulin. In this way it is possible to show that there are absolutely no differences between both age groups indicating mature transport systems for endogenous amino acids as early as in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Renal transport of endogenous amino acids. II. Influence of treatment with triiodothyronine or dexamethasone in immature and adult rats.

Repeated administration of triiodothyronine (T3, 20 micrograms/100 g b.w., once daily for 3 days) or dexamethasone (60 micrograms/100 g b.w., once daily for 3 days) caused significant changes of amino acid plasma concentrations in young (10 days old) and adult rats (2 months old). After treatment with T3, in young animals concentrations of beta-alanine, aspartic acid, glutamic acid, ornithine, asparagine, leucine, taurine, serine, alanine, and glutamine were enhanced, whereas those of tyrosine, arginine, and threonine were significantly diminished. In adult rats only slight changes occurred after both T3 and dexamethasone. In the kidney, the reabsorbed fraction of amino acids was enhanced after both T3 and dexamethasone treatment in young rats, whereas in adult rats the two hormones were without influence on tubular reabsorption of amino acids. Taken together, both different plasma concentrations of amino acids and changes in amounts of amino acids reabsorbed in the tubuli, in adult rats the fractional excretion of amino acids was nearly unchanged following hormone treatment (exception: significant increase in taurine clearance). But in young animals the fractional excretion was reduced in 15 of 22 amino acids after dexamethasone and in 12 of 23 amino acids after T3 treatment, indicating stimulatory effects of both hormones on tubular amino acid carrier systems in immature animals.

Aging↗

[Sodium and chlorine reabsorption system in the kidney of fetal and neonatal rats].

It has been demonstrated that already to the end of embryonic period, foetal rats have rather developed kidney system which is sensitive to one of the most effective diuretics--furosemide (lasix), an inhibitor of chloride channels. Investigation of the activity of transport ATPases revealed the developed system of sodium transport in the kidney of foetal rats.

Absorption↗