Renal effects of atrial natriuretic factor in the rats of different ages

Renal effects of an atrial natriuretic factor preparation were compared in 15, 28 and 66-day-old rats. This factor, prepared from atrial tissue of adult rats, was more effective in 28 and 66-day-old rats than in 15-day-old rats. There was a 6 fold increase of sodium excretion in 15-day-old rats and a 60 fold increase in 28-day-old rats. There was also a 15 fold increase in renal sodium excretion in 66-day-old rats receiving a higher dose (0.1 ml/animal). As indicated by the sodium potassium ratio, the increase in renal excretion of sodium was distinctly more pronounced than the increase in renal potassium excretion. In 15, 28 and 60-day-old rats, the increase of urine volume was 2 fold, 4 fold and 5 fold, respectively. The increase of fractional sodium excretion (FE) in rats receiving an atrial factor preparation was distinctly more pronounced than the increase of GFR. In all experiments, the preparation from ventricular tissue of the same animals was ineffective in producing natriuresis or diuresis.     

Antidiuretic action of prolactin in the rat with diabetes insipidus.

Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.     

The effect of the anions, phosphate and sulphate, on normal rates of excretion of potassium in dogs.

Small doses of (NH4)2HPO4 or KH2PO4 by stomach tube caused increase in plasma PO4 and PO4 excretion. Above a threshold of 0-8 mmol. 1(-1), increase of plasma PO4 by 0-5 mmol. 1(-1) caused PO4 excretion to increase by about 35 mumol. min.-1 After KH2PO4 this relationship was not altered by the concurrent increases in plasma K and K excretion. After doses of (NH4)2SO4 or K2SO4, excretion of SO4 was similarly related to plasma SO4 and was independent of plasma K and K excretion. An effect of PO4 on K excretion was observed after doses of (NH4)2HPO4, when increased excretion of PO4 was accompanied by increased excretion of K without change in plasma K. There was also increased excretion of NH4 and a small increase in Na excretion. The changes were similar to those produced by (NH4)2SO4 [O'Connor and Summerill, 1976]. KH2PO4 and K2SO4 produced increase in plasma K and increased excretion of K not significantly different from the changes produced by KCl or KHCO3 [Baylis and O'Connor, 1976]. After KH2PO2 or K2SO4, the urinary anion was PO4 or SO4, instead of Cl and HCO3. Any effect of anions on K excretion was much less than the effect of increase in plasma K. At low rates of excretion of K, increased urinary excretion of impermeant anion can determine increased excretion of K. However, the effect of anion is small in comparison with the effect of increase in plasma K.     

Special effects of a complex probiotic containing cellulolytic bacteria Cellulomonas on actively growing rabbits

It was shown that the association of probiotic bacteria of the genuses Bacillus and Cellulomonas form biolayers on the surface of beet marc particles. The positive effect of a fodder additive that contained the biolayer on the basis of a phytomatrix on the growth and development of young rabbits was shown. Feeding of animals with a mixed fodder that contained 0.1% preparation resulted in stimulation of digestion of all components of the food. Among other components of the mixed fodder, cellulose was digested most effectively. An increase in the biomass of symbiotic bacteria and enzymatic activity in the blindgut chymus was also observed. The positive nitrogen balance demonstrated an increase in the nitrogen content in animals and a decrease of its losses with excretion. The mechanism of response of the rabbit’s organism to introduction of the complex probiotic preparation into the digestive tract is discussed.     

Acidification of the bathing fluid by the skin of Rana pipiens in metabolic acidosis

The skin of Rana pipiens can be shown to excrete H+ in an in vitro preparation. This H+ excretion is increased by placing the frog in metabolic acidosis. In addition, H+ excretion is increased by the presence of HCO-3-CO2 on the serosal or inside surface of the skin. Removal of Na+ from the outside bathing solution of the skin has no apparent effect on H+ excretion. Ouabain inhibits H+ excretion by the skin of acidotic frogs almost completely, in the absence of exogenous CO2. In the presence of 5% CO2 ouabain inhibits H+ excretion by 50%. In the acidotic frog skin the H+ excretion was reduced by abolishing the spontaneous potential difference. While in the normal skin there was no effect. When the P.d. was clamped at -10 to -100 mV there was no effect on H+ excretion, while there was a slight depression of H+ excretion when the P.d. was clamped at +10 to +100 mV (outside to inside the skin). In the presence of 5% CO2 there was a marked depression of H+ excretion when clamped at -10 to -100 mV in the normal skin. In metabolic acidosis there was a marked stimulation when clamped at -10 to -100 mV.     

Effects of parathyroid hormone on H+ and NH+4 excretion in toad urinary bladder.

The urinary bladder of Bufo marinus excretes H+ and NH+4, and the H+ excretion is increased after the animal is placed in metabolic acidosis. The present study was done to determine if parathyroid hormone could stimulate the bladder to increase the excretion of H+ and/or NH+4. Parathyroid hormone added to the serosal solution in a final concentration of 10 mug/ml was found to increase H+ excretion by 50 per cent above the control hemibladders, while there was no effect on NH+4 excretion. Parathyroid hormone had no effect on H+ excretion when added to the mucosal solution. We also performed experiments utilizing theophylline and dibutyryl cyclic AMP which mimicked those of the parathyroid hormone experiments. A dose-response analysis was performed and the results indicate that 1 mug/ml of parathyroid hormone was the minimal effective dose. These results suggest that parathyroid hormone can stimulate H+ excretion in the toad urinary bladder and this effect seems to be mediated by cyclic AMP. In addition, it was found that parathyroid hormone has no effect on NH+4 excretion.     

The Effects of Probenecid and Thiazides and Their Combination on the Urinary Excretion of Electrolytes and on Acid-base Equilibrium

The effects of commonly used therapeutic doses of hydrochlorothiazide and probenecid, given singly and in combination, on the urinary excretion of monovalent and divalent ions and on acid-base equilibrium were studied in four patients with idiopathic hypercalciuria.Probenecid had no effect on the urinary excretion of monovalent ions but resulted in a sustained increase in the urinary excretion of calcium, magnesium and citrate and a temporary increase in the urinary excretion of ammonium, in addition to its well-known effects on uric acid metabolism. A temporary fall in serum phosphorus levels was also observed.Probenecid also modified the response to hydrochlorothiazide in that the urinary excretion of calcium, magnesium and citrate was greater during combined therapy than when hydrochlorothiazide was administered alone. Probenecid prevented or abolished the increase in serum uric acid levels associated with the use of thiazide but did not modify the effects of hydrochlorothiazide on the urinary excretion of sodium, chloride, potassiu, phosphorus, ammonium, titratable acid and bicarbonate.     

Triamcinolone activation of renal ammonia production.

The effects of scillaren and dinitrophenol on bilirubin excretion by the perfused rat liver were studied. Both compounds inhibited bile flow, scillaren by 20 to 40%, and dinitrophenol by 60 to 80%. Bilirubin excretion was also impaired. However, the effect of scillaren on bilirubin excretion was less than that on bile flow, as indicated by an increase in the bile bilirubin concentration, whereas dinitrophenol had a greater effect on bilirubin excretion than on bile flow. Dinitrophenol also inhibited the hepatic removal of unconjugated bilirubin from the perfusate, probably because it impaired the initial uptake and/or storage of unconjugated bilirubin by the perfused liver.     

Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis.

It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.     

Renal handling and acute urinary electrolyte effects of aminoglycoside antibiotics: Use of a solitary renal autotransplant in the conscious sheep

Renal handling of the aminoglycoside antibiotics gentamicin and tobramycin were studied before and after one hour of constant intravenous infusions adjusted to maintain a concentration of 15 μg/mL. A solitary renal autotransplant model in four conscious volume replete 40 Kg sheep was used. This unique surgical preparation allows sampling of renal arterial and renal venous blood as well as urine drained through an exteriorized parotid-ureteral fistula. This surgical preparation has considerable potential in renal pharmacology since it uses a conscious, large animal. Baseline studies in this preparation demonstrated normal, ⁵¹CrEDTA and ¹²⁵I PAH, clearances which were unaffected by the drugs. Aminoglycoside binding to pooled sheep sera was 11% at physiologic PH. calcium and magnesium concentrations. A–V difference was 1.3 ± .3 μg/mL and extraction by the kidney was 9 ± 3.2% with no differences between gentamicin and tobramycin. Clearance of gentamicin was 84% and tobramycin 86% of GFR. There was no evidence of tubular injury as evidenced by unchanged urinary beta-2 microglobulin excretion. Serum Na, K, Ca and Mg did not change over the course of the study. Both drugs caused a prompt decrease in absolute and fractional sodium excretion while only gentamicin produced a kaliuresis. Early aminoglycoside effects on electrolyte balance may be an eventual determinant of nephrotoxic potential rather than differences in renal drug handling.Nephrotoxicity is a major side effect of aminoglycoside antibiotic therapy. Although gentamicin and tobramycin have similar pharmacokinetics, including renal cortical accumulation, both double blind clinical studies (1) and experimental data (2) have shown that gentamicin is more frequently associated with renal dysfunction. Recent studies in the dog have suggested that hypokalemia due to renal potassium wasting is a risk factor predisposing to nephrotoxicity (3). In clinical usage aminoglycosides may induce hypokalemia and hypocalcemia, perhaps resulting from drug-induced magnesium depletion (4). Previous studies reporting data concerning the acute effects of aminoglycosides on renal function and electrolyte excretion have used anesthetized animals (5) or isolated perfused kidney preparations (6). The present experiments utilize a unique surgical preparation in which a solitary kidney is autotransplanted to the neck of a sheep followed by a contral ateral nephrectomy. Urine flow is exteriorized through a uretero-parotid-cutaneous fistula thus providing a conscious animal with ready access to renal arterial and renal venous blood. Our results show that renal handling of gentamicin and tobramycin do not differ during short-term constant infusions. Both drugs caused a decrease in sodium excretion while gentamicin caused a larger increase in fractional and absolute potassium excretion. This raises the possibility that nephrotoxic properties of aminoglycosides may be secondary to their effects on electrolytes.     

Alloxan-induced luminol luminescence as a tool for investigating mechanisms of radical-mediated diabetogenicity.

It is not clear whether the muscle wasting commonly observed in hyperthyroidism is due to alteration in the rate of protein synthesis or degradation. The effect of experimental hyperthyroidism on skeletal-muscle proteolysis in the rat was studied by measuring alanine and tyrosine release from isolated skeletal muscles in vitro and 3-methyl-histidine excretion in vivo. Alanine release from the isolated epitrochlaris-muscle preparation was increased as soon as 24h after a 25 microgram dose of L-tri-iodothyronine in vivo. Conversely, alanine release from muscles of hypothyroid rats was decreased, but restored by L-tri-iodothyronine supplementation before death. Furthermore, 3-methylhistidine excretion was increased in hyperthyroid rats throughout an 18-day treatment period. The increased amino acid release from isolated muscles and the increased 3-methylhistidine excretion in vivo strongly suggests that hyperthyroidism increases skeletal-muscle proteolysis. Furthermore, the thyroid-hormone concentration may be an important factor in regulating muscle proteolysis.     

Intensification of the excretory flow of plutonium-239 from the body in the late stage of its metabolism

The paper deals with the effect of iron preparations on the excretion of plutonium 239 from a body at a later stage of the radionuclide metabolism. The experimental results show that oral administration of the iron preparation at a later stage of 239Pu metabolism enhances the radionuclide excretion both in urine and in faeces. On the basis of the results obtained the coefficients are calculated for 239Pu excretion in urine and faeces and for its content in the organs of deposition. This may be used for increasing the sensitivity of indirect dosimetry of plutonium-239 within the body.     

Hormonal regulation of biliary calcium excretion in rats: inhibition of calcitonin action by alpha 1-adrenergic stimulation

The effect of synthetic [Asu1,7] eel calcitonin (CT) and other hormones on biliary calcium excretion was investigated in rats cannulated bile duct. Administration of CT (80 mU/100 g body weight) produced a significant increase in liver calcium and a corresponding elevation of bile calcium content. The increase in bile calcium content was also caused by administration of insulin (0.1 U/100 g), epidermal growth factor (10 micrograms/100 g), glucagon (10 micrograms/100 g), epinephrine (10 micrograms/100 g), norepinephrine (10 micrograms/100 g), 4 beta-phorbol 12-myristate-13-acetate (10 micrograms/100 g) and ATP (1.0 mg/100 g), suggesting that this increase may be a receptors-mediated response. Of these hormones and drugs, norepinephrine, a alpha-receptor mediator, clearly prevented CT effect on biliary calcium excretion. Moreover, phenylephrine, a alpha 1-receptor agonist, caused an inhibition of the CT effect, while the agonist significantly increased biliary calcium excretion. The present study clearly demonstrates that biliary calcium excretion is stimulated by various hormones which increase calcium influx into liver cells, and suggests that the CT action may be inhibited by alpha 1-adrenergic stimulation.     

Evidence for an intrarenal renin‐angiotensin system in the European lesser‐spotted dogfish

The existence of an intrarenal renin‐angiotensin system (RAS) in a perfused European lesser‐spotted dogfish Scyliorhinus canicula trunk preparation was examined by the inhibition of angiotensin‐converting enzyme by captopril. This resulted in a glomerular diuresis, an increase in urea and chloride clearance and excretion, and an increase in transport maxima for glucose. It is proposed that these results suggest the presence of an intrarenal RAS.     

Effect of Resection of Lung Tumours on the Steroid Abnormalities in Patients with Lung Cancer

The urinary excretion of androsterone, aetiocholanolone, total 17-oxosteroids, and 17-hydroxycorticosteroids (17-OHCS) was measured in 40 patients with lung cancer three days before resection and again 10-15 days after resection of their lung tumours. There was a significant postoperative increase in the excretion of 17-OHCS but a significant decrease in the excretion of androsterone and aetiocholanolone, resulting in an increase of the preoperative abnormalities in steroid excretion in these patients. Since there was no change in steroid excretion towards normal after resection of the lung tumours, it seems that the steroid abnormalities found in lung cancer are not the effect of the presence of the lung tumours. As the excretions of 17-OHCS and 11-deoxy-17-oxosteroids change in opposite directions after resection, it is suggested that a dissociation of factors that control the excretion of these two groups of steroids takes place as a response to surgical stress in patients with lung cancer.     

Identification of an extracellular nucleotide pyrophosphatase in the culture media of Streptomyces mediterranei ME/R 17]

An exocellular pyrophosphatase, active on the nucleotide precursors of peptidoglycans, has been found in the culture medium of Streptomyces mediterranei ME/R 17. This enzyme was separated from the DD-carboxypeptidase by batchwise adsorption on DEAE cellulose. The pyrophosphatase had no strict substrate requirements, it hydrolyzed various UDP-sugar substrates: UDP-GlcNAc, UDP-Mur NAc and UDP-MurNAc peptides, giving rise to the corresponding sugar phosphate and to UMP. The enzyme preparation also contained a 5'-nucleotidase activity and UMP was further split to give uridine. This nucleotidase activity was inhibited by potassium tetraborate. Both cytoplasmic and particulate preparations from cells of S. mediterranei also contained a pyrophosphatase activity while only the particulate fractions showed the DD-carboxypeptidase activity. The pyrophosphatase excretion was tested during the grwoth cycle. The activity of the enzyme showed a constant increase throughout the exponential growth and a stronger increase in the late exponential phase. Such a result could be correlated with a consumption of the nutrients in the culture medium, in fact a relatively poor culture medium had a strong positive effect upon the production of the exocellular pyrophosphatase.     

Possibilities of using MIGI-K protective activity under conditions of radionuclide contamination

Experimental studies of the mussel hydrolyzate (MIGI-K) have shown that this preparation can enhance both general and radiation resistance of the organism. Moreover, MIGI-K promotes elimination of incorporated radionuclides from the organism. Some properties of this preparation, in particular, the absence of toxicity or harmful side effects, have made it possible to apply MIGI-K as an adaptogen, that is, a food supplement oftherapeutic and preventive action used to increase radionuclide excretion in the Chernobyl emergency clean-up workers.     

The effect of magnesium sulfate infusion on systemic and renal prostacyclin production

Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4.     

Comparative Trial of Nutrizym in Chronic Pancreatic Insufficiency

A cross-over trial of pancreatic replacement therapy was carried out in 12 adults with chronic pancreatic insufficiency. The standard enteric-coated preparation, Pancrex V forte, was compared with Nutrizym, which has an enteric-coated core of pancreatic extract and a shell of bromelains—a mixture of proteolytic enzymes derived from the stem of the pineapple.Nutrizym was significantly more effective than Pancrex V forte in improving fat absorption, and reduced faecal weight. Protein digestion was assessed by measuring the urinary excretion of hydroxyproline after a gelatin meal. Nutrizym produced an earlier and significantly higher peak in hydroxyproline excretion than Pancrex V forte, but the cumulative effect was similar. The value of bromelains was investigated by including a period on the Nutrizym core alone. This was similar to Pancrex V forte in improving fat absorption but had less effect on protein digestion, suggesting that the beneficial effect of Nutrizym compared with Pancrex V forte was due to the added bromelains, and not to differences in enzyme content or enteric coating.     

Stimulation of renal tubular transport by ethacrynic acid in rats of different ages.

The transport system for organic acids in the kidney is not fully developed in the neonatal period. The effect of repeated administrations of ethacrynic acid on the renal excretion of p-aminohippurate (PAH) was studied in rats of different ages. Pretreatment with ethacrynic acid was followed by an increase in the renal excretion of PAH in 33-, 55-, 105- and 240-day-old rats but not in newborn rats. In 55-day-old rats the increase in renal excretion of PAH after pretreatment with ethacrynic acid was not associated with any consistent change of the glomerular filtration rate. It is concluded from these results that the stimulation of transport processes in the kidney by ethacrynic acid and some other drugs is linked with their affinity to tissue proteins.