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Biomedical subjects

F Gross

Publications and source records attributed to F Gross.

At least 19 recordsLinked to original sources
PubMed1979

The pharmacological relevance of vital staining with neutral red.

The uptake of neutral red into the renin-containing juxtaglomerular granules does not inhibit the release of renin either in basal or in stimulated states of renin secretion. The vasodilating effect of neutral red may be due to a nonspecific binding to noradrenaline-receptors in the vascular smooth muscle cells.

Angiotensin II↗
PubMed1979

Production of antibodies against bradykinin.

High-titer antibodies against bradykinin were raised in rabbits. 2 different conjugates of bradykinin were used for immunization: bradykinin coupled to human serum albumin via 1,5-difluoro-2,4-dinitrobenzene and bradykinin coupled to edestin via 1-ethyl-3(3-dimethyl-aminopropyl)-carbodiimide. The sensitivity of the radioimmunoassay method is in the range of 1-50 pg of bradykinin. Cross-reaction of anti-bradykinin antisera occurred with kallidin and met-lys-bradykinin.

Animals↗
PubMed1979

[Absorption and excretion of g-strophanthin after intravenous or sublingual administration (author's transl)].

Tritiated g-strophanthin was administered to six volunteer patients in a dose of 0.25 mg intravenously and 6.0 mg sublingually 1-3 weeks apart. Radioactivity in plasma and urine was measured afterwards for 48 or 96 hours, respectively. Plasma concentration fell to about a fifth of the maximal concentration within 6 min after intravenous administration, total excretion within three days being about 50%, with a half-time of 11 hours. Measurable plasma concentration after sublingual administration was demonstrable only after 15 min in some and after 2 hours in all the six patients. Radioactivity counts increased up to the 24th hour, in three patients up to the 48th hour. Maximal plasma concentration ranged from 4.7 to 0.7 ng/ml, corresponding to levels reached 15 min or 4 hours, respectively, after intravenous administration. Urinary radioactivity reached its maximum after 24-48 hours and then decreased. Within three days 0.6 and 2.5% of the administered radioactivity was recovered, corresponding to the g-strophanthin doses of 0.072 to 0.3 mg. The findings once again confirm the low and irregular absorption of g-strophanthin when administered sublingually or orally.

Administration, Oral↗
PubMed1979

Constraints of drug regulation on the development of new drugs.

A review is given of the various regulations for the preclinical and clinical evaluation of new drugs, their effects on the clearance of new medicines for general use by practising physicians, and their repercussion on industrial drug research. Undoubtedly, extensive and continuously increasing regulatory procedures, which in addition have to be satisfied repeatedly in individual countries, claim an unproportionally high percentage of the industrial capacity for research and development of new drugs, leaving too little for basic research, which is a prerequisite for the discovery of new medicines that are more than just "me too" products. Despite the fact that regulatory language differs from scientific attitude and arguments, the wall of regulations should be neither too thick nor too high to impede research and to hinder the prompt application of important new drugs. Even the most sophisticated and extensive drug regulations cannot prevent the use of drugs which is not indicated, because it is impossible to regulate ignorance. To regulate drugs is necessary, but the governments and their drug agencies should also encourage drug research and should support industry in the development of new drugs. On the other hand, the drug companies must adhere to the accepted standards and create an atmosphere of confidence by presenting reliable and complete data.

Drug Industry↗
PubMed1979

Vascular reactivity in the pathogenesis of spontaneous hypertension.

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar-Kyoto (WK) rats; dose-response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.

Angiotensin II↗
PubMed1979

Effect of neonatal sympathectomy by 6-hydroxydopamine on volume and resistance regulation in stroke-prone spontaneously hypertensive rats.

1. Neonatal sympathectomy with 6 hydroxy-dopamine (6-OHDA) was used as a tool to assess the significance of an increased sympathetic vascular tone for the development of high blood pressure in stroke-prone spontaneously hypertensive rats. After administration of 6-OHDA the rise in blood pressure was blunted for the following 9 weeks until innervation was re-established. 6-OHDA-treated rats retained more sodium and had larger plasma and blood volumes than sham-treated rats. 2. Catecholamines in plasma were increased 2-10-fold immediately after sympathectomy, but their concentrations were subnormal on day 7. Eight weeks after sympathectomy plasma noradrenaline and dopamine were not elevated, but plasma adrenaline has increased twofold. 3. The reactivity of resistance vessels to noradrenaline was markedly enhanced and the neuronal uptake and metabolism of noradrenaline were still reduced 8 weeks after neonatal sympathectomy. 4. These results confirm the significance of an intact sympathetic nervous system for the development in these rats. Sodium retention and increased plasma and blood volume may be considered as a compensatory mechanism for the vasodilatation resulting from decreased vasomotor tone.

Animals↗
PubMed1979

Hemodynamic changes during the development of sodium-induced hypertension in subtotally nephrectomized rats.

Hemodynamic changes during the development of sodium-induced hypertension were investigated in male Sprague-Dawley rats after about 70% of the renal mass was removed. Throughout the four experimental weeks, subtotally nephrectomized rats on a high sodium diet (750 mEq/kg) showed a continuous rise in blood pressure up to the mean value of 178 +/- 9 mmHg. In sham-operated animals on the high sodium supply the blood pressure did not increase as compared to sham-operated controls on the standard sodium diet (150 mEq/kg). In the hypertensive group, the primary changes were urea retention and a concomitant increase of serum osmolarity, but the serum sodium concentration remained at the normal level. These changes were followed by sustained enlargement of extracellular fluid and relative intravascular volumes, together with a simultaneous increase of heart rate and blood pressure. During high sodium intake, the plasma renin activity in subtotally nephrectomized rats was suppressed to one fifth of that in sham-operated animals, but the renin substrate activity did not increase markedly.

Animals↗
PubMed1978

Effects of vasopressin and its deamino-D-arginine analogue on renin release in the isolated perfused rat kidney.

The direct action of arginine-vasopressin (AVP) and its deamino-D-arginine analogue (DDAVP) on renin release (RR) has been studied in isolated rat kidneys perfused with an electrolyte solution at constant pressure in a single-pass system. AVP and DDAVP infused at various concentrations (80 to 2100 pg/ml and 80 to 8700 pg/ml, respectively) reduced volume and increased osmolality of urine in a dose-dependent way. High doses of AVP reduced renal perfusate flow and glomerular filtration rate while DDAVP had no effect on renal haemodynamics. When vasoconstrictor doses of AVP or high concentrations of DDAVP were infused, "basal" RR remained unchanged. However, when RR had been stimulated by infusion of isoproterenol, vasoconstrictor doses of AVP as well as high doses of DDAVP which did not increase renal vascular resistance diminished RR by about 30% (P less than 0.01, and P less than 0.05, respectively). These results suggest that the inhibition of RR by vasopressin is not related to its vasoconstrictor action.

Animals↗
PubMed1978

[Histomechanical studies on test specimens from hyaline cartilage under compressive loading with regard to rheology (author's transl)].

Modified rheological methods from high polymer physics (biorheology, historheology) have been applied to the testing of hyaline cartilage histomechanics. The following histomechanical properties of cartilage are discussed: transient behaviour, the influence of the mechanical history on the subsequent force-deformation processes, viscoelastic equilibrium status (histomechanical steady state), and relaxation phenomena in the pressure and tension range under alternating pressure-tension loading. Pressure force-time input and output curves in a closed loop system and the amplitude-increasing phenomenon under uniform sinus deformations with increasing superimposed linear deformation input were also demonstrated. The results are discussed from the point of view of functional anatomy.

Animals↗
PubMed1978

Effect of saralasin and serum in myohaemoglobinuric acute renal failure of rats.

1. In rats deprived of food and water for 24 h acute renal failure was produced by the intramuscular injection of glycerol. Eight hours later plasma urea concentration had increased threefold despite a small rise in urine volume. Plasma concentrations of renin and renin substrate were elevated. 2. When saralasin, a competitive antagonist of angiotensin II, was infused for 8 h after glycerol injection, urine volume and plasma urea were similar to values in rats that had received an infusion of saline. 3. Administration of rat serum (4.5 ml h-1 kg-1) for 4 h suppressed plasma renin concentrations, but plasma urea increased to the same extent as in rats without serum. 4. When saralasin and serum were infused at the same time, urine volume, urine osmolality and solute excretion increased and the rise of plasma urea was diminished. 5. Saralasin has a protective effect against glycerol-induced acute renal failure only when volume is replaced concomitantly.

Acute Kidney Injury↗
PubMed1978

Renal vasoconstriction in glycerol-induced acute renal failure. Studies in the isolated perfused rat kidney.

1. Acute renal failure was produced in rats by the intramuscular injection of glycerol (6.1 mol/l 10 ml/kg). Either 2 or 4--6 h later the right kidney was isolated and perfused for 1 h with an electrolyte solution containing a gelatin preparation (Haemaccel, 35 g/l) at pressures between 90 and 100 mm Hg in a single-pass system. 2. In kidneys taken from rats with acute renal failure renal vascular resistance was markedly increased immediately after the start of the perfusion as compared with control kidneys taken from untreated rats. During the following 30 min of perfusion the resistance progressively decreased and, at 1 h of perfusion, was similar to that in control kidneys or only moderately elevated. 3. Despite the reduction of renal vascular resistance glomerular filtration rate was still markedly increased immediately after the start of the perfusion as compared with control kidneys taken from untreated rats. During the following 30 min of perfusion the resistance progressively decreased and, at 1 h of perfusion, was similar to that in control kidneys or only moderately elevated. 3. Despite the reduction of renal vascular resistance glomerular filtration rate was still markedly impaired after 1 h of perfusion and fractional reabsorption of sodium and water as well as the secretion of p-aminohippurate were diminished. Renal venous renin concentration and renin release were lower in kidneys taken from rats with acute renal failure than in the control experiments. 4. These results suggest that the increase in renal vascular resistance and the stimulation of renin release after injection of glycerol in vivo are the consequence of extra- rather than intra-renal mechanisms.

Acute Kidney Injury↗