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Biomedical subjects

M Pellet

Publications and source records attributed to M Pellet.

At least 19 recordsLinked to original sources

Improved analogs and novel delivery systems for somatostatin octapeptides.

Appropriate N-terminus modification can result in somatostatin (SRIF) octapeptide analogs that are both more potent and more selective in vitro for the human SRIF receptor type 2 (hsst2). In addition, these modifications can improve the duration of action and bioavailability of SRIF analogs following parenteral administration, as shown by both pharmacological and distribution studies in vivo with BIM-23190 and BIM-23197 in the rat.

Amino Acid Sequence↗

Acute effect of high dose (48 mg) of piretanide in advanced renal insufficiency.

1 The acute effects of a high dose of piretanide, a new potent diuretic were studied in eight patients with severely impaired renal function (GFR between 0.09 and 0.17 ml s-1 1.73 m-2). 2 After hydration and following two control periods, a single dose of 48 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Urinary fluid losses were replaced orally (100 ml of water ever hour) and intravenously (isotonic saline + glucose infusion). 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Piretanide (48 mg) appeared to be effective in advanced renal insufficiency, producing a significant increase in urine flow rate, in sodium, chloride, potassium and calcium excretion and in Cosm. 5 There was no significant change in GFR, as measured by inulin clearance, or in the other measured parameters.

Adult↗

Piretanide and urinary excretion of ions in rat. Effect of indomethacin.

1. Piretanide is a new loop diuretic resembling furosemide. The effects of this diuretic on various parameters of renal function and on the excretion of the major ions were studied on anaesthetized, hydrated rats. 2. Piretanide induced a marked diuresis and increased sodium, potassium, chloride and calcium excretion. Calcium excretion increased more than that of sodium. Urinary osmolality and water reabsorption decreased. 3. Inulin clearance and phosphate excretion were significantly altered by piretanide. 4. Pretreatment of rats with indomethacin did not suppress the effects of piretanide on diuresis nor its effects on urinary excretion of sodium, chloride and potassium, since these parameters increased in the same proportion in the presence or in the absence of indomethacin. 5. Pretreatment with indomethacin abolished piretanide-induced dissociation of sodium and calcium excretions.

Animals↗

Fate of glutamate carbon and nitrogen in isolated guinea-pig kidney-cortex tubules. Evidence for involvement of glutamate dehydrogenase in glutamine sythesis from glutamate.

1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the release of 14CO2 from L-[1-14C]glutamate (which gives an estimation of the flux of glutamate carbon skeleton through alpha-oxoglutarate dehydrogenase) clearly indicated that, despite the absence of ammonia accumulation, glutamate metabolism was initiated by the action of glutamate dehydrogenase and not by transamination reactions as suggested by Klahr, Schoolwerth & Bourgoignie [(1972) Am. J. Physiol. 222, 813-820] and Preuss [(1972) Am. J. Physiol. 222, 1395-1397]. Additional evidence for this was obtained by the use of (i) amino-oxyacetate, an inhibitor of transaminases, which did not decrease glutamate removal, or (ii) L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which caused an accumulation of ammonia from glutamate. 5. Addition of NH4Cl plus glutamate caused an increase in both glutamate removal and glutamine synthesis, demonstrating that the supply of ammonia via glutamate dehydrogenase is the rate-limiting step in glutamine formation from glutamate. NH4Cl also inhibited the flux of glutamate through glutamate dehydrogenase and the formation of glucose, alanine and lactate. 6. The activities of enzymes possibly involved in the glutamate conversion into pyruvate were measured in guinea-pig renal cortex. 7. Renal arteriovenous-difference measurements revealed that in vivo the guinea-pig kidney adds glutamine and alanine to the circulating blood.

Aminooxyacetic Acid↗

Activity of a new high efficiency diuretic in man: piretanide (HOE 118).

1 The pharmacological actions of piretanide, a new high efficiency diuretic, were studied in sixteen patients with GFR (inulin clearance) varying from 0.1--2.5 ml/s. 2 After hydration and following two control periods, a single dose of 6 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Fluid losses were replaced. 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Main results showed piretanide was efficient in the group with normal GFR (inulin clearance greater than 1.5 ml/s) and in the group with slightly decreased GFR (1.0 less than inulin clearance less than 1.4 ml/s), in terms of diuresis, natriuresis, kaliuresis and calciuresis. It was inefficient in the group with severe renal insufficiency (inulin clearance less than 0.3 ml/s). 5 Free water clearance showed preservation of diluting ability to a large extent. 6 In the three groups, no significant change in inulin clearance and PAH clearance occurred.

Adult↗

Effect of acidosis, alkalosis and monofluoroacetate administration on citrate and ATP content of rat renal medulla and papilla.

1. --Renal distribution of citrate showed that there is an increase in citrate content from cortex to medulla and a decrease from medulla to papilla. Alkalosis produced an increase in citrate content and acidosis a decrease in renal citrate content, in each of the studied renal area. Monofluoroacetate produced no significant change in citrate content of medulla or papilla; it did not interfere with the acido-basic related changes in cortex citrate content, but its effect was additive. 2. --Renal distribution of ATP significantly decreased from cortex to medulla and from medulla to papilla. Acid or basic diet had no influence on intratissular ATP content. Fluoroacetate decreased renal ATP content.

Acidosis↗

A new device for differentiated tissue sampling in rat kidney.

Since freeze-clamping does not allow to sample the diffrent renal areas a new method of kidney tissue sampling in anesthetized rats is described. It consists in sectioning a slice in the middle of the rat kidney and immediately freezing. This device allows quick and accurate separation of the different renal areas, and especially of the papilla which is almost entirely sampled. Complete freezing is obtained within 7s after clamping of the renal artery. As proof of adequate "in vivo" fixing, adenine nucleotide levels were assessed in each tissue sample. ATP concentration in cortex samples was 1.62 +/- 0.33 mumole/g wet tissue, this value is comparable with those obtained in the cortex by freeze-clamping.

Adenine Nucleotides↗

Glutamine metabolism in isolated dog kidney tubules: inhibition by dialysed albumin preparation.

The metabolic fate of L-glutamine (1 and 5 mM) was studied in isolated dog kidney tubules. At 1 and 5 mM substrate concentration, and after 60 min of incubation, glucose represented 40% and 25% of the glutamine removed; the glutamine unaccounted for (which was probably completely oxidized) represented about one-half and one-third of glutamine removal at 1 and 5 mM glutamine concentrations, respectively. Due to contaminating fatty acids, addition of dialysed bovine serum albumin (fraction V) greatly altered the metabolic fate of glutamine. This observation emphasizes the need for using albumin with great caution for experiments with kidney tubules.

Albumins↗

In vitro citrate synthesis by the dog kidney. Investigations with cortex, red and white medulla slices.

In vitro utilization or production of citrate by the cortex, outer medulla or inner medulla of dog kidney was measured. Our data show: 1. An in vitro citrate synthesis or utilization capacity of the cortex greater than that of the red medulla. 2. An effect of pH on citrate synthesis or utilization capacity of the cortex, an effect not seen with medullary slices. 3. An absence of citrate synthesis or utilization by white medulla slices. It would seem that the citrate found in the white medulla and the papilla of the dog kidney in vivo was not produced in situ.

Animals↗

Lactate and pyruvate metabolism in isolated renal tubules of normal dogs.

The kinetics of lactate and pyruvate (1 and 5 mM in each case) metabolism was studied in isolated dog renal tubules. Utilization of these two substrates and the production of glucose, pyruvate, or lactate, and alanine were determined. The rates of lactate and pyruvate utilization and of glucose production were constant during 60 min of incubation. Glucose production from pyruvate was less than that from lactate. Addition of albumin to the incubation medium greatly inhibited lactate and pyruvate utilization at both substrate concentrations. It stimulated, however, glucose production from 1 mM, but not 5 mM, lactate or pyruvate. These effects were found to be due to the presence of fatty acids in the albumin solution used. In the absence of fatty acids, glucose production represented 35 to 40% of lactate uptake, but represented less than 20% of pyruvate uptake. Fatty acids markedly enhanced the percentage of transformation of lactate and pyruvate into glucose, and that of pyruvate into lactate. Alanine represented 20% or less of lactate and pyruvate uptake. These results suggest that fatty acids have a regulatory influence on lactate and pyruvate dog kidney metabolism.

Alanine↗

Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function.

The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy.

Acebutolol↗

[Changes in renal function in the hours following an intravenous injection of acebutolol].

A study was carried out, of the changes of renal functional value and of urinary electrolytes excretion after rapid intravenous injection of acebutolol in twelve subjects with various glomerular filtration. Renal functional value was estimated by measuring inuline. P.A.H., urea and creatinin clearances during a control period of thirty minutes and during the four hours following administration of acebutolol. The variations in the excretion of electrolytes: chloride, sodium, potassium, calcium and phosphorus were measured during the same periods. The following results were obtained: in subjects with normal renal functional value, administration of acetubolol brings about: a variation which is under 20 p.cent of glomerular filtration and P.A.H. clearance; a 50 p.cent average decrease of natriuresis. in cases of renal insufficiency: clearances of inuline and P.A.H. are unchanged. There is a 20 p.cent average decrease of natriuresis. There is a decrease of urinary output (35-45 p.cent) and of urea clearance (20-50 p.cent).

Acebutolol↗

Intrarenal distribution of citrate in the dog during antidiuresis and diuresis.

The intrarenal distribution of citrate was evaluated in the dog during antidiuresis and osmotic diuresis, by using the specific citrate assay method of Moellering and Gruber. The measurements were made on tissue samples taken from four different regions throughout the kidney: cortex, outer and inner medulla, and papilla. During antidiuresis, a characteristic distribution of citrate was observed with highest levels in the papilla and lowest ones in the outer medulla. A medullary concentration gradient for citrate was found. Mannitol greatly decreased papillary citrate and sodium, but no changes in outer and inner medullary citrate occured. The results could not be explained by the citrate contained either in the trapped urine or blood in the tissue. It is suggested that citrate accumulation in the inner regions of renal medulla may be accounted for by countercurrent mechanisms or regional differences in renal citrate metabolism.

Animals↗

Investigation of electrical impedance variations of dog brain tissue during experimental metabolic disturbances.

Experiments were carried out on dogs using bielectrode probes having as adequate impedancemeter. The probe is introduced via a cranial opening into the grey matter. This gives the following: a low frequency reading which is related to the extra cellular fluid component; a high frequency reading which is related to the total overall liquids; and a proportionality ratio of these liquids in the explored volume. The impedance variations are functions of the nature and intessity of vascular disturbance. Variation of the low frequency impedance (5 kHz) is the most significant. The experimental prodedure consists of: 1) Abrupt and permanent circulatory arrest; 2) Circulatory reduction by haemorrhage followed by recovery (if necessary by means of blood transfusion); 3) Anoxia by CO inhalation, recovery affected by means of O2 inhalation; and 4) Hypoglycemic coma induced by intravenous injection of insulin. The changes in the biochemical state of the cerebral tissue give very large variations of the low frequency impedance. It is these variations which are to constitute the object of this communication.

Animals↗