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Biomedical subjects

M Hropot

Publications and source records attributed to M Hropot.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pharmacodynamics and pharmacokinetics of furosemide combinations with potassium-retaining and thiazide-like diuretics: clearance and micropuncture studies.

The interaction between furosemide on the one hand and hydrochlorothiazide, tizolemide, amiloride and triamterene on the other was studied by clearance and micropuncture techniques in rats. Simultaneous administration of furosemide with hydrochlorothiazide and tizolemide distinctly increased the natriuresis compared to that induced by furosemide alone, whereas the potassium excretion diminished. In contrast, amiloride and triamterene primarily decreased furosemide-induced fractional potassium excretion by about 30%, whereas sodium excretion increased only slightly compared to that produced by furosemide alone. Hydrochlorothiazide and triamterene significantly decreased furosemide secretion and changed its pharmacokinetics. Furosemide plasma concentration increased, thus possibly prolonging the salidiuretic effect. Amiloride and tizolemide did not influence the secretion of furosemide at all.

Animals↗
PubMed1986

Enzymuria in streptozotocin-diabetic rats.

Twenty four hour urine samples of male control and streptozotocin-diabetic Wistar rats were analysed for a series of commonly known kidney-specific enzymes, for electrolytes, creatinine, glucose, total protein and urine volume. The examination was done during two periods of 5 days between the 25th and 30th and the 32nd and 36th day after streptozotocin application. In the first period the animals had free access to food and water, whereas in the second period on days 32, 34 and 36 food was withdrawn. In the first observation period the diabetic rats showed increased excretion rates of 15 measured urinary parameters, while alanine aminopeptidase (EC 3.4.1.2) and gamma-glutamyltransferase (EC 2.3.2.2) activities were lowered and inorganic phosphate was unchanged. The removal of food resulted in decreased excretion values for alanine aminopeptidase, gamma-glutamyltransferase and total protein as compared with fasted nondiabetic animals. The activities of N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), acid phosphatase (EC 3.1.3.2), lactate dehydrogenase (EC 1.1.1.27), pyruvate kinase (EC 2.7.1.40), C1-fructose 1.6-diphosphatase (EC 3.1.3.11) and the excretion values for sodium, calcium, magnesium, chloride and glucose were higher than in fasted nondiabetic rats. beta-Glucosidase (EC 3.2.1.21), potassium, inorganic phosphate, creatinine, and urine volume showed no differences between fasted diabetic and fasted control animals. The enzymes in the renal cortex at the end of the experiment showed only decreased activity of alanine aminopeptidase in diabetic rats. Lactate dehydrogenase, pyruvate kinase, beta-glucosidase, C1-fructose 1.6-diphosphatase and glucose 6-phosphatase (EC 3.1.3.9) were increased and gamma-glutamyltransferase, N-acetyl-beta-D-glucosaminidase, acid phosphatase and glucose 6-phosphate dehydrogenase (EC 1.1.1.49) showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of rat atriopeptin III on renal function in dogs during water diuresis and hydropenia.

Experiments have been performed in conscious male beagle dogs under maximal water diuresis or hydropenia to determine the effects of synthetic rat atriopeptin III [r-AP III = r-ANF- (103-126)] (Geller et al. 1984), in an intravenous dose of 50 micrograms/kg body weight, on renal function and plasma renin activity. Intravenous injection of r-AP III resulted in an increase in urine and sodium excretion lasting up to 20 minutes, while the glomerular filtration rate and renal plasma flow were hardly influenced under either of the experimental conditions. r-AP III induced an increase in free water clearance from 7.51 +/- 2.45 ml/min in controls to 12.15 +/- 2.25 ml/min in the first clearance period, whereas the free water reabsorption was only slightly reduced (5.56 +/- 1.22 vs. 5.02 +/- 1.23 ml/min). r-AP III caused a slight increase in plasma renin activity from 0.65 +/- 0.46 in controls to 1.02 +/- 0.47 ng X ml-1 X h-1 in water diuretic dogs and from 3.19 +/- 0.51 in controls to 3.72 +/- 0.81 ng X ml-1 X h-1 in hydropenic dogs. These experiments show that the r-AP III-induced salidiuretic response seems not to be mediated by changes in the glomerular filtration rate and renal plasma flow. Moreover, the increase in free water clearance and the absence of change in free water reabsorption indicate a proximal site of action of r-AP III.

Animals↗
PubMed1985

Tubular action of diuretics: distal effects on electrolyte transport and acidification.

We used clearance and free-flow micropuncture techniques to evaluate the influence of several diuretic agents, given both individually and in various combinations, on transport of sodium, potassium, and fluid, and on acidification and ammonium transport, within the distal tubule of the rat kidney. The loop diuretics, furosemide and piretanide, sharply increased fractional delivery of fluid, sodium, and potassium into the distal tubule, and, as a result, sodium reabsorption and potassium secretion were enhanced in this nephron segment. These two drugs also stimulated urinary acidification and increased urinary phosphate, titratable acid, and ammonium excretion. These effects took place both within the loop of Henle and along the distal tubule. Amiloride and triamterene alone inhibited distal tubular sodium reabsorption and potassium secretion, and, when given with one of the loop diuretics, suppressed both the kaliuresis and the increased acid and ammonium excretion induced by the latter agents. Hydrochlorothiazide and tizolemide inhibited sodium reabsorption within the distal tubule, and were associated with a stimulation of potassium secretion within this segment. Addition of one of these two latter distally acting agents to either of the loop diuretics led to a further augmentation of sodium excretion, but to a reduction of potassium excretion, compared to the responses seen after the loop diuretics alone.

Ammonia↗
PubMed1985

Enzymuria of the rat: biorhythms and sex differences.

Alanine aminopeptidase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase were measured daily over 65 days in 24-hour urine of male and female Wistar rats. The mathematical evaluation was based on the Fourier-analysis. The excretion of alanine aminopeptidase and gamma-glutamyltransferase was higher in male than in female rats. This sex-dependent difference was not observed for N-acetyl-beta-D-glucosaminidase. The excretion of the 3 enzymes followed a biorhythm with a dominant period of 7 days for gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase and one of 9 days for alanine aminopeptidase. Biorhythms and sex differences of enzymuria should be considered in experimental designs.

Acetylglucosaminidase↗
PubMed1985

Na+-K+ cotransport and hypertension. Effect of piretanide and hydrochlorothiazide on red blood cell sodium concentration in acutely salt-loaded hypertensive and normotensive rats.

Na+-K+ cotransport has been presumed to be a genetic marker or aetiological factor in essential hypertension in numerous studies. In spite of extended in vitro research, the role of this transport system in hypertension could not be proved. In the present study the action of the cotransport inhibitor piretanide and the non-loop diuretic hydrochlorothiazide (HCT) on red blood cell (RBC) sodium concentration was examined under in vivo conditions in spontaneously hypertensive rats (SHR) and normotensive Sprague Dawley rats (NSDR) during acute salt-loading. Before drug administration salt-loading resulted in an increase of RBC sodium concentration, the percentage of which was not different in SHR and NSDR. However, after administration of piretanide in oral doses of 8-32 mg/kg body weight, the percent increase in RBC sodium was lower in SHR than in NSDR. This effect which was found to be dose-dependent was not brought about by HCT. The data might be due to a piretanide inhibition of sodium-induced inward RBC Na+-K+ cotransport more pronounced in SHR than in NSDR.

Animals↗
PubMed1983

5-sulfamoylorthanilic acids, a sulfonamide series with salidiuretic activity.

A series of 4,N-disubstituted 5-sulfamoylorthanilic acids was synthesized by nucleophilic substitution reactions starting either from 2,4-dihalogeno-5-sulfamoylbenzenesulfonic acids or, in most cases, from phenyl 2,4-dihalogeno-5-sulfamoylbenzenesulfonates. The latter method is based on the relative stability of the phenoxysulfonyl group to nucleophiles, e.g., amines, phenols, and thiols, and the possibility of smooth hydrolytic or hydrogenolytic cleavage as a final step, with formation of the SO3H group. On evaluation of these compounds for salidiuretic activity in rats orally (po), and in dogs orally and intravenously (iv), a number of highly active substances was found; the best had a threshold dose of 0.02 mg/kg po in dogs. The results are given in tables, and the structure-activity relationships within the series are discussed. Besides the known effect of the phenoxy radical, an outstanding activating effect was shown by the butylsulfonyl and cycloalkylsulfonyl radicals and by the N-methylanilino radical in particular when they were located in the 4-position of the orthanilic acid molecule. The sulfanilic acid isomers corresponding to three of the most active compounds were synthesized and proved to be completely inactive in rats.

Animals↗
PubMed1983

Enzymuria of the rat: the preparation of urine for enzyme analysis.

The effects of sample preparations by dialysis and gel filtration on the catalytic concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and beta-glucuronidase are described. Individual urines were collected during 24 hours on 3 consecutive days from 10 male rats. Gel filtration (Sephadex G25) was more effective than dialysis against water in the removal of inhibitors of N-acetyl-beta-D-glucosaminidase and beta-glucuronidase. For alanine aminopeptidase, slightly higher results were obtained by dialysis. Inhibitor contents varied from day to day. Activity decreases of beta-glucuronidase and N-acetyl-beta-D-glucosaminidase were found in some of the urine samples and interpreted as removal of activators. Gel filtration is recommended for the preparation of rat urine for the measurement of these three enzymes. The slightly inferior effect of gel filtration on alanine aminopeptidase should be disregarded for the sake of practicality.

Acetylglucosaminidase↗
PubMed1982

[Contribution to the problem of preventing recurrences of oxalate and phosphate urinary caluli: active modification of citrate excretion and Ca++-binding capacity in the urine of Wistar rats].

Citric acid may well be, quantitatively and in terms of complex chemistry, the most important of the organic acids capable of binding Ca++ in urine. Since the quantitative determination of citrates in urine became a routine method in many research-orientated urological laboratories thanks to the introduction of standardized enzymatic tests, reports of a reduced excretion of citrates in patients with (recurrent) (oxalate) calculi have become frequent. During our long-term study of patients with recurrent formation of calculi we also observed a clear deficit of citrates in their morning, midday and evening urine. The conspicuous incidence of calculi when there is a concurrence of hypocitraturia and alkaline urine (RTA, in animal experiments: acetazolamide) clearly suggests the lithoprotective significance of citric acid. By quantitatively testing a large number of organic compounds which are interesting both structurally and in terms of complex chemistry, it has been possible to find some substances which restrict crystallization, raise the level of citrates and bind Ca++. A few have also found to restrict the excretion of oxalate in Wistar rats.

Animals↗
PubMed1982

[Search for a new rinsing solution for the local lysis of calcium-containing urinary calculi].

Due to improved rinsing techniques local chemolitholysis is again becoming more important. Good result good results in the local chemolysis of phosphate calculi (calculi caused by remains of Struvit) with Renacidin and other rinsing solutions (Fam, Rossier, Gittes, Jacobs, Smith, Royle, Nemoy, Stamey) have led to a revival chemolitholysis (Alken) in the last 4--5 years, however only in the case of phosphate calculi, which account for 60--80%, cannot be dissolved by Renacidin, as is explicitly pointed out by the manufacturer. The experiments carried out by the group headed by Kallistratos and Timmermann in the 60's using rinsing solutions based on EDTA were discontinued, probably because of physiological reservations concerning the chemicals used and the long duration of treatment at physiologically tolerable concentrations and pH values. In order to extend the range of rinsing solutions to be tested, we tested new substances, including some which complex not only the anion (oxalate) but also the cation (Ca). Alternating treatment with oxalate binding and Ca binding rinsing solutions has been found to give particularly good results.

Calcium Oxalate↗
PubMed1981

[In vitro and first in vivo experiments for the dissolution of calcium-containing urinary calculi (author's transl)].

There are numerous reports dealing with the significantly reduced citrate secretion in (recurrent) tone formers. The critical values of the Ca/citrate ratio in the nocturnal urine of (oxalate) stone formers has also been reported, emphasizing the need of medicaments being capable to increase the citrate secretion and to raise the basal citrate level of the nocturnal urine in these patients. In our in vitro experiments, we tested quantitatively the inhibitory activity of some new substances on crystal growth. In Wistar rats we measured the Ca2+-binding capacity as well as the citrate and oxalate excretion before and after oral application of a great number of new compounds. Some of them were highly efficacious in the reduction of the Ca-oxalate activity product, as can be derived from the increased Ca2+-binding capacity and/or the decreased oxalate secretion in urine.

Acetates↗
PubMed1981

[Detection of urinary organic acids by gradual titration of pH 2,0-7,4. Significance for the assessment of the litho-protective characteristic of the examined urine].

The role of organic acids in urine is not sufficiently known until today. From our detailed in vitro studies it can be concluded that some of them are highly efficacious in the inhibition of Ca-oxalate and Ca-phosphate crystal growth. Moreover, some of them showed, as acids and as salts, a strong lytic effect on stone-forming crystals and native stone-material. By the oral application to rats, concentrations preventing any precipitation out of meta- and instable Ca-oxalate solutions could be achieved. The renal excretion was controlled by the stepwise titration of preacidified urinary samples from pH 2.0 to 7.4 and the lithoprotective character of urine estimated by the Ca2+-binding capacity.

Animals↗
PubMed1980

[Pharmacokinetic problems in surgery].

The article deals with the shortcomings of pharmacokinetic models in predicting tissue-concentrations of drugs. Several examples are shown from our group that cooperation of surgeons and pharmacokinetic researchers is necessary to overcome these shortcomings.

Biological Availability↗