PubMed Health⌕ Search

Biomedical subjects

B Ferrier

Publications and source records attributed to B Ferrier.

35 records · Page 2Linked to original sources
PubMed1993

Effect of valproate, sodium 2-propyl-4-pentenoate and sodium 2-propyl-2-pentenoate on renal substrate uptake and ammoniagenesis in the rat.

Experiments were carried out in the intact functioning rat kidney to study the effect of valproate (VPA), a widely used antiepileptic drug and an hyperammonemic agent, but usually without clinical relevance, and of two of its metabolites, sodium 2-propyl-4-pentenoate (4-en-VPA) and sodium 2-propyl-2-pentenoate (2-en-VPA), on the renal production of ammonia and on the renal uptake of glutamine, glutamate and of inhibitors of renal ammoniagenesis; mainly lactate, fatty acids, ketone bodies and alpha-ketoglutarate. Administration of VPA and 4-en-VPA stimulated the uptake of glutamine and glutamate and the production of ammonia by the rat kidney, resulting in an increase in the renal venous release of ammonia and in a hyperammonemia. By contrast, no hyperammonemia was observed after the administration of 2-en-VPA which stimulated renal ammoniagenesis to a lesser extent than VPA and 4-en-VPA, resulting in no stimulation of the renal venous release of ammonia. The three compounds tested caused, in a qualitatively different but, in terms of substrate carbons, in a quantitatively similar manner, a significant diminution of the renal uptake of fatty acids, ketone bodies and alpha-ketoglutarate. These results suggest that, in the rat kidney, VPA, 4-en-VPA and 2-en-VPA stimulate the production of ammonia at least in part by reducing the renal uptake and metabolism of ammoniagenesis inhibitors; the more potent stimulation of renal ammoniagenesis caused by VPA and 4-en-VPA also suggest that these compounds exert their stimulatory effect by an additional mechanism.

Ammonia↗
PubMed1992

Transport of beta-hydroxybutyrate and acetoacetate along rat nephrons: a micropuncture study.

The transport of ketone bodies across the luminal membrane of the nephron was studied by means of micropuncture techniques in rats in normal acid-base state. The concentration of beta-hydroxybutyrate (beta-HB) and acetoacetate (AcAc) in plasma, tubular fluid and urine was measured by an ultramicromethod using enzymatic cycling. At endogenous plasma ketone body concentration, approximately 80% of the filtered load of beta-HB and AcAc was reabsorbed in the proximal convoluted tubule, the remaining fraction being almost completely reabsorbed between the late proximal convoluted and the distal tubule; under these conditions, the urinary excretion of ketone bodies was less than 1% of the filtered load. A progressive elevation to steady-state levels of plasma beta-HB resulted in a progressive reduction of the fractional reabsorption of beta-HB and AcAc in the proximal convoluted tubule, which means that reabsorption of ketone bodies in this nephron segment is saturable. No net secretion of ketone bodies could be demonstrated along the nephron even at the highest plasma ketone body concentrations reached. In clearance experiments, the capacity of the rat kidney for reabsorbing both beta-HB and AcAc was found to be limited by a maximal tubular capacity (Tm). The data suggest that, in the young Wistar rat nephron, most of the reabsorption of ketone bodies is carrier mediated.

3-Hydroxybutyric Acid↗
PubMed1990

An enzymatic cycling method for 3-acetylpyridine adenine dinucleotide to increase the sensitivity of enzymatic methods which employ this NAD analog.

The NAD analog 3-acetylpyridine adenine nucleotide (APAD), because of its higher oxidation potential, has proven useful for the direct enzymatic measurement of such compounds as lactate, malate, glutamate, etc., for which the equilibrium with NAD+ as oxidant is unfavorable. An enzymatic cycling method which is capable of increasing the sensitivity of such reactions 10,000-fold or more is described. The APADH produced in the original stoichiometric reaction is used to catalyze a cycling reaction that employs lactate and malate dehydrogenases (EC 1.1.1.27 and EC 1.1.1.37) to generate (from lactate plus oxalacetate) very large quantities of pyruvate and malate. After the cycling step, the malate formed is measured with NAD+ and with malate dehydrogenase, plus aspartate aminotransferase, and oxaloacetate to pull this indicator reaction to completion. The application of this cycling method is illustrated by analysis of malate in the range 1 to 10 pmol.

Coenzymes↗
PubMed1990

Effect of microgravity on metabolic enzymes of individual muscle fibers.

Eleven enzymes were measured in individual fibers of soleus and tibialis anterior (TA) muscles from two flight and two control (synchronous) animals. There were five enzymes of glycogenolytic metabolism: phosphorylase, glucose-6-phosphate isomerase, glycerol-3-phosphate dehydrogenase, pyruvate kinase, and lactate dehydrogenase (group GLY); five of oxidative metabolism: citrate synthase, malate dehydrogenase, beta-hydroxyacyl-CoA dehydrogenase, 3-ketoacid CoA-transferase, and mitochondrial thiolase (group OX); and hexokinase, subserving both groups. Fiber size (dry weight per unit length) was reduced about 35% in both muscles. On a dry weight basis, hexokinase levels were increased 100% or more in flight fibers from both soleus and TA. Group OX enzymes increased 56-193% in TA without significant change in soleus. Group GLY enzymes increased an average of 28% in soleus fibers but underwent, if anything, a modest decrease (20%) in TA fibers. These changes in composition of TA fibers were those anticipated for a conversion of about half of the originally predominant fast glycolytic fibers into fast oxidative glycolytic fibers. Calculation on the basis of fiber length, rather than dry weight, gave an estimate of absolute enzyme changes: hexokinase was still calculated to have increased in both soleus and TA fibers, but only by 50 and 25%, respectively. Three of the OX enzymes were, on this basis, unchanged in TA fibers, but 3-ketoacid CoA-transferase and thiolase had still nearly doubled, whereas TA GLY enzymes had fallen about 40%. In soleus fibers, absolute levels of OX enzymes had decreased an average of 25% and GLY enzymes were marginally decreased.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1990

Effect of lithium on renal transport and utilization of alpha-ketoglutarate in the rat.

Experiments were carried out in the intact functioning rat kidney to study the effect of lithium on both the renal transport of alpha-ketoglutarate (alpha-KG) along the nephron by micropuncture techniques and the renal uptake and peritubular transport of alpha-KG by measuring the renal blood flow, the urinary flow and the rate of renal alpha-KG delivery, filtration, reabsorption or secretion and excretion. At endogenous plasma alpha-KG concentration, 2.3 mM plasma lithium caused an increase in the fractional excretion of alpha-KG, whereas 4.6 mM plasma lithium led to a net secretion of alpha-KG. The micropuncture data indicate that this secretion occurred between the late proximal and the distal tubule, i.e., in the pars recta and/or in the loop of Henle. When plasma alpha-KG concentration was elevated, the two doses of lithium used inhibited the reabsorption of alpha-KG both in the proximal tubule and in the pars recta and/or the loop of Henle. Renal arteriovenous measurements reveal that, at low plasma alpha-KG concentrations, lithium caused a significant decrease in both the renal uptake of alpha-KG and the peritubular transport of this organic anion. These results suggest that the alpha-KG secreted in the pars recta and/or the loop of Henle was synthesized within the renal cells of the latter segments and not transported from the blood to the tubular lumen. At higher plasma alpha-KG concentrations, both the peritubular transport and the renal reabsorption were reduced by lithium.

Absorption↗
PubMed1989

Transport and utilization of alpha-ketoglutarate by the rat kidney in vivo.

In order to establish the characteristics of net renal transport and utilization of alpha-ketoglutarate (alpha-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of alpha-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, alpha-KG uptake was higher than alpha-KG reabsorption at both endogenous and elevated plasma alpha-KG concentrations; thus, a net peritubular transport, which was the main supplier of alpha-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of alpha-KG occurred at blood alpha-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of alpha-KG. At endogenous plasma alpha-KG concentrations, alkalosis converted net renal uptake into net renal production of alpha-KG resulting in addition of alpha-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood alpha-KG concentration restored the renal uptake of alpha-KG. This uptake, which was entirely accounted for by the peritubular transport of alpha-KG, reached a maximum which was lower than that observed in normal and acidotic rats.

Acid-Base Equilibrium↗
PubMed1988

Valproate-induced stimulation of renal ammonia production and excretion in the rat.

Administration of valproate, a widely used antiepileptic drug, markedly stimulated the production of ammonia by the rat kidney, resulting in an increase in both the renal venous release and the urinary excretion of ammonia. These effects were associated with a diminution of the plasma concentration of urea which was not accompanied by a stimulation of the urinary excretion of urea. These results indicate that the kidneys, together with the liver, might contribute to the hyperammonaemia caused by valproate.

Ammonia↗
PubMed1988

Billing patterns of general practitioners and family physicians in Ontario: a comparison of graduates of McMaster Medical School with graduates of other Ontario medical schools.

This descriptive study which uses data obtained from the Ontario Health Insurance Plan has identified a number of differences in the style of practice chosen by general practice/family medicine (gp/fm) physicians who graduated from McMaster medical school from that of other contemporary Ontario gp/fm graduates who are practicing in Ontario. McMaster gp/fms were more likely to be certified in Family Medicine, saw fewer patients per month than the comparison group, and billed less services but the cost per service billed was somewhat higher.

Curriculum↗
PubMed1985

Reabsorption and secretion of alpha-ketoglutarate along the rat nephron: a micropuncture study.

The transport of alpha-ketoglutarate (alpha-KG) across the luminal membrane of the rat nephron was studied by micropuncture and microassay techniques. In normal and acidotic rats, approximately 75% of the filtered alpha-KG was reabsorbed in the proximal tubule and 20% in the pars recta and/or loop of Henle at endogenous plasma concentration of alpha-KG. A progressive elevation to steady-state levels of plasma alpha-KG resulted in a progressive reduction of the fractional reabsorption of alpha-KG in the proximal tubule as well as in a progressive increase in the fractional reabsorption of alpha-KG in the pars recta and/or loop of Henle. At plasma alpha-KG concentration 20-40 times above normal, reabsorption of alpha-KG was found to be limited by a maximal tubular capacity. In alkalotic rats, net secretion of alpha-KG in the early proximal convoluted tubule, net reabsorption in the remainder of the proximal convoluted tubule, and net secretion in the pars recta and/or loop of Henle were observed. These micropuncture data indicate that, depending on the acid-base conditions, net reabsorption or net secretion of alpha-KG may occur in at least two distinct sites along the rat nephron.

Acid-Base Equilibrium↗
PubMed1983

Renal excretion of ascorbic acid in the rat: a micropuncture study.

Ascorbate concentration was measured by high-performance liquid chromatography and amperometry in plasma, tubular fluid, and urine from rats infused with ascorbic acid to steady-state levels. At a low concentration of ascorbate in plasma (Pasc = 0.2 mM) reabsorption occurred along the proximal convoluted tubule (PCT). The fractional delivery (FD) of ascorbate [(TF/P)asc/(TF/P)polyfructosan] to the late proximal convoluted tubule was 0.64 +/- 0.04, and the fractional excretion of ascorbate (FEasc) was 0.56 +/- 0.01. At higher Pasc (0.9 mM) net secretion occurred in the PCT, while the FDasc was 1.5 +/- 0.2 to the early and 1.8 +/- 0.2 to the late PCT. At still higher Pasc the secretory and the reabsorptive transports were saturated and the FDasc and FEasc approached unity, indicating that reabsorptive as well as secretory transport occurs in the proximal tubule. In clearance experiments the reabsorptive transport and secretory transport were inhibited by 2-nitroprobenecid. The drug induced a fall of FEasc when infused at a low rate (0.9 mumol X kg body wt-1 . min-1), which was followed by an increase in FEasc when the rate of infusion of 2-nitroprobenecid was increased to 3 mumol . kg body wt-1 X min-1.

Animals↗
PubMed1983

Effects of p-aminohippurate and pyrazinoate on the renal excretion of salicylate in the rat: a micropuncture study.

The inhibitory effects of p-aminohippurate and pyrazinoate (PZA) on the transport of salicylate were studied by free-flow micropuncture in the rat. p-Aminohippurate (5, 10 or 25 mumol/kg X min) and PZA (10 or 25 mumol/kg X min) inhibited proximal tubular secretion of salicylate; they induced decreases in the fractional delivery of salicylate to the late proximal tubules. In alkalotic rats, the late proximal decrease in fractional delivery of salicylate was accompanied by a decreased fractional excretion of salicylate. In contrast, such a decrease in fractional excretion of salicylate was not observed in rats in normal acid-base balance. A greater rate of PZA infusion (25 mumol/kg X min) not only inhibited secretion, but also depressed a reabsorptive carrier-mediated transport of salicylate. Thus, in alkalotic rats, fractional delivery of salicylate to late proximal tubules were 1.90 +/- 0.15, 0.90 +/- 0.10 and 1.34 +/- 0.13, respectively, for control rats and rats infused with 10 or 25 mumol/kg X min of PZA. The corresponding values of fractional excretion of salicylate were 1.21 +/- 0.09, 0.61 +/- 0.05 and 0.08 +/- 0.09, respectively. The data suggest that salicylate is secreted as well as reabsorbed by carrier-mediated mechanisms and that there may be two secretory mechanisms.

Aminohippuric Acids↗
PubMed1979

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↗
PubMed1978

The neurotoxicity of valine deficiency in rats.

When valine, an essential amino acid, was withdrawn from the diet of weanling rats, the animals rapidly developed a unique pattern of neurological symptoms characterized by head retraction, staggering and aimless circling. At necropsy degenerative changes were most prominent in the neurons of the red nuclei, brain stem structures which modulate motor function. To explore the pathogenesis of the neurotoxicity associated with valine deficiency, we fed rats purified diets deficient in valine alone or in valine plus other branched chain and neutral amino acids, and we examined brain tissues by light microscopy. Motor disfunction and red nuclei damage occurred only in rats fed diets lacking valine alone and not in rats fed diets lacking all three branched chain amino acids. These results suggest that the neurotoxicity of valine deficiency results from amino acid imbalance rather than from lack of dietary valine per se.

Animals↗
PubMed1975

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↗
PubMedDate not supplied

Substrate uptake and utilization by the kidney of fed and starved rats in vivo.

In order to obtain information (1) on the quantitative contribution of various circulating substrates to renal metabolism and (2) on the relative importance of net luminal and basolateral transport for substrate uptake, we have precisely quantified the renal blood flow, the urinary flow, and the rates of substrate handling by the kidney of anesthetized fed and 72-hour-starved rats. For this, the concentration of twelve metabolites were simultaneously measured in arterial and venous whole blood and plasma as well as in urine of each rat thanks to the use of microassays based on enzymatic cycling. In fed rats, the main potential energy sources were glucose and lactate followed by fatty acids, ketone bodies, citrate and glycerol. Starvation caused a large increase in renal uptake and metabolism of fatty acids, ketone bodies, glutamine and glycerol, and a large inhibition of lactate utilization. The net peritubular uptake of acetoacetate, citrate, glycerol and free fatty acids demonstrated in both nutritional states was increased by starvation only for glycerol and free fatty acids; net peritubular efflux of both beta-hydroxybutyrate and ammonium ions was stimulated whereas that of glutamine was converted into net peritubular uptake by starvation.

Animals↗