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Biomedical subjects

M J Arnaud

Publications and source records attributed to M J Arnaud.

At least 19 recordsLinked to original sources
PubMed1995

Caffeine demethylation measured by breath analysis in experimental liver injury in the rat.

To assess the effects of experimental liver injury on caffeine metabolism, 1 muCi/kg b.w. of [3-methyl 14C]-caffeine (together with 5 mg/kg b.w. of the cold compound) was injected i.p. to four different experimental groups and respective controls of unanesthetized male Sprague-Dawley rats. Exhaled 14CO2 was completely collected during 4 h and peak exhalation rate and fraction of dose recovered were calculated. 1/3 hepatectomy affected 14CO2 exhalation to a limited extent, decreasing solely peak exhalation rate (p < 0.05 compared to sham-operated controls). 2/3 hepatectomy, on the other hand, resulted in significant reduction (p < 0.01) in both peak exhalation rate (by 59%) and fraction of dose recovered (by 47%), that were proportionate to the loss of liver mass (59%). End-to-side portocaval shunt led to the well-documented hepatic "atrophy", liver weight being diminished on average to 50% within 2 weeks of surgery; however, reductions in peak exhalation rate (by 75%) and fraction of dose recovered (by 64%) were even more pronounced. Finally, 48 h bile duct ligation was equivalent to "functional 2/3 hepatectomy", peak exhalation rate (by 65%) and fraction of dose recovered (by 56%) being markedly diminished despite increased liver weight. These results indicate that 14CO2 exhalation curves following administration of specifically labelled caffeine are quantitative indicators of acute or chronic loss of functioning liver mass. In addition, the 3-demethylation pathway appears to be particularly sensitive to the inhibitory effects of cholestasis on microsomal function.

Animals↗
PubMed1995

Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women.

The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.

Adult↗
PubMed1992

Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.

Acidosis↗
PubMed1991

Metabolic effects in rats of a diet with a moderate level of medium-chain triglycerides.

Energy intake, weight gain, carcass composition, plasma fuels, hepatic metabolites and lipogenic enzyme activities were studied in adult rats fed either a low fat, high carbohydrate (LF) diet or one of two fat-containing diets in which 32% of the metabolizable energy was constituted by long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Compared with the LF diet, the MCT diet did not depress food and energy intake, weight gain, energy and nitrogen retention or lipid deposition and did not produce ketogenesis. The weight gain of rats fed LCT was 25% higher, and increased lipid deposition was observed. Lower lipogenic enzyme activities were observed in rats fed the LF diet containing 4% corn oil than in rats fed the MCT diet containing 1% corn oil. This effect disappeared when rats previously adapted to the LCT diet were fed LF or MCT diets containing 1% corn oil for 21 d. By d 21, in both groups, hepatic malic enzyme, ATP-citrate lyase, acetyl CoA carboxylase and fatty acid synthase activities were 2.2-, 2.0-, 2.3- and 1.8-fold higher than those of rats fed LCT. Intermediate hepatic glucose-6-phosphate dehydrogenase activities were observed in rats fed the MCT diet, compared with LCT (40% lower) and LF (1.6-fold higher) diets. These data show that in rats fed a diet in which MCT supplies 32% of metabolizable energy, a high activity of lipogenic enzymes is observed, suggesting that MCT had no inhibitory effect on the activity of these enzymes.

Animals↗
PubMed1990

Metabolism of maltitol by conventional rats and mice and germ-free mice, and comparative digestibility between maltitol and sorbitol in germ-free mice.

The metabolism of maltitol (4-alpha-D-glucosylsorbitol) was assessed in fasting conventional (C) rats, C mice and germ-free (GF) mice, using [U-14C]maltitol. The radiorespirometric patterns of 14CO2 collected for 48 h after the administration of labelled maltitol were characterized by a constant rate of 14CO2 production lasting 4 h for both C rats and mice. The pattern for the GF mice showed a peak at the second hour followed immediately by a slow decrease. The percentage recovery of 14CO2 was significantly lower for the GF mice (59%) compared with C animals (72-74%). Urine, faeces and intestinal contents after 48 h totalled 19% of the administered radioactivity in the C rats and mice and 39% in the GF mice. The digestibility of maltitol and the absorption of sorbitol in GF mice was also assessed. The caecum and small intestine of GF mice, 3 h after administration of equimolar quantities of maltitol (140 mg/kg body-weight) or sorbitol (70 mg/kg body-weight), contained 39 and 51% of the ingested dose respectively, present mostly in the caecum as sorbitol. The alpha-glucosidase (maltase) (EC3.2.1.20) activity of the small intestine was appreciably higher (1.5-1.7 times) in the GF mice than in the C mice. These results suggest that the enzymic activities in the small intestine of mice and rats are sufficient to hydrolyse maltitol extensively. Consequently, the slow absorption of sorbitol seems to be an important factor limiting the overall assimilation of maltitol in the small intestine.

Animals↗
PubMed1989

Comparison of in vitro, animal, and clinical determinations of iron bioavailability: International Nutritional Anemia Consultative Group Task Force report on iron bioavailability.

Relative bioavailability of two iron fortificants, electrolytic Fe and ferric orthophosphate, was related to that of the reference ferrous sulfate with in vitro and rat model depletion-repletion methods in four laboratories to compare values directly with those obtained in a parallel human study. In vitro testing was performed on Fe compounds with both solubility and dialysis in a simulated in vitro gastrointestinal digestion system. Two depletion-repletion techniques, hemoglobin-regeneration efficiency (HRE) and an official method of the Association of Official Analytical Chemists (AOAC), were examined. AOAC relative biological values (RBV) of electrolytic Fe were 0.66 and 0.78 and of FePO4 were 0.25 and 0.34. HRE values were 0.78 and 0.58 for electrolytic Fe and FePO4, respectively. When compared with FeSO4 in a radiolabeled farina-based meal fed to humans, the RBV of FePO4 was 0.25 and electrolytic Fe 0.75. Results obtained with the AOAC method serve as the most reliable prediction of Fe bioavailability in the human although in vitro dialysis is a promising screening technique.

Animals↗
PubMed1989

Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms.

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of beta-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (beta-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27 +/- 5 mumol/liter (P less than 0.02) due to a 22 +/- 6% decrease in leucine flux (P less than 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P less than 0.02). Leucine oxidation decreased by 36 +/- 8% (P less than 0.01 vs. controls). beta-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P less than 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via beta-adrenergic mechanisms (P less than 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.

Adrenergic beta-Antagonists↗
PubMed1988

Effects of moderate physical training on prednisone-induced protein wasting: a study of whole-body and bone protein metabolism.

This study investigated the possibility of preventing prednisone-induced protein wasting by regular physical activity. Eight healthy untrained volunteers took prednisone (30 mg/d for nine days), once after a 4-week exercise program that consisted of jogging 2.5 miles four times a week, and once without exercise. Whole body protein turnover was measured from the 15N enrichment plateau of urinary ammonia during ingestion of 15N glycine at hourly intervals. Whole-body protein synthesis and breakdown were derived from nitrogen flux, nitrogen intake, and urinary nitrogen elimination. Muscle myofibrillar protein breakdown was explored by measuring urinary 3-methylhistidine excretion. Bone protein metabolism was studied by measuring serum bone GLA protein (BGP), a specific marker of bone protein synthesis, and urinary elimination of hydroxyproline, an index of bone resorption. Whole-body protein turnover was significantly increased by exercise and prednisone (+19% and +17%, respectively); this effect was related to increased protein synthesis during exercise training (+27%, P less than .01) and to increased protein breakdown during prednisone administration without exercise (+21%, P less than .05). In contrast, values of protein turnover, synthesis, and breakdown were not different from control when the subjects took prednisone after training. Urinary excretion of 3-methylhistidine was decreased (-15%, P less than .05) at the end of the prednisone administration period but was identical to the control value when the subjects took prednisone in association with exercise. In contrast, serum BGP was significantly decreased by prednisone, with or without exercise (-35%, P less than .001). These data suggest that moderate exercise training can prevent, at least in part, the protein loss induced by prednisone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Synthesis, effectiveness and metabolic fate in cows of the caesium complexing compound ammonium ferric hexacyanoferrate labelled with 14C.

Adding ammonium ferric hexacyanoferrate (AFCF) to cows' fodder produced after the Chernobyl nuclear accident prevented milk contamination by increasing the faecal elimination of 137Cs. Synthesis of ammonium ferric hexa[14C]-cyanoferrate (AF14CF) and its purification were performed for the study of the metabolic fate of this complex, and the evaluation of the possible release of cyanide. The stability of this colloidal product, tested by anaerobic incubation in rumen juice in vitro, showed no release of free cyanide from AF14CF, but hexacyanoferrate was identified in the rumen juice and 0.13% of the added radioactivity was converted to labelled CO2. AF14CF administered per os to two cows showed a nearly quantitative excretion of radioactivity in faeces during the first 3 d (91-95%). A very low but significant level of radioactivity appeared in plasma, blood cells, expired CO2 and was detected in organs taken 9 d after administration. Total cumulative radioactivity in urine and milk amounted to 0.19-0.47% and 0.068-0.071% respectively for the two cows. Labelled hexacyanoferrate and thiocyanate were identified in the urine and also in faeces. In spite of this relative instability of AFCF in the rumen of cows, the poor absorption of AF14CF degradation products showed that AFCF constitutes an efficient and safe food additive to prevent the absorption of radioactive caesium from ruminant feed and its secretion in milk.

Accidents↗
PubMed1988

[Long-term consumption of a diet with moderate medium chain triglyceride content does not inhibit the activity of enzymes involved in hepatic lipogenesis in the rat].

The activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40), ATP-citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase were lower (-25 to -60%) in liver of rats fed during 45 days with a moderate long-chain triglycerides (LCT) content diet (32% of metabolizable energy, ME), than in control rats fed with a low fat diet (LCT, 10% of ME). However, the fall in malic enzyme activity was not significant. In contrast, these activities were higher (+40 to +160%) in rats fed with a diet with a moderate medium-chain triglycerides (MCT) content (32% of ME), than in control rats. Nevertheless, the increase in activity of malic enzyme and ATP-citrate lyase was more important. Contrary to LCTs, MCTs had no inhibitory effect on the activity of enzymes involved in hepatic lipogenesis.

ATP Citrate (pro-S)-Lyase↗
PubMed1987

Rapid and complete urinary elimination of [14C]-5-hydroxymethyl-2-furaldehyde administered orally or intravenously to rats.

5-Hydroxymethyl-2-furaldehyde (HMF), is a major product of sugar degradation found in food and solutions used in parenteral nutrition. Labeled [14C]HMF was synthesized by dehydration of [14C]fructose on ion-exchange resin and administered per os (po) and intravenously (iv) to rats. Metabolic balance of radioactivity demonstrated that HMF or its metabolites are rapidly eliminated in the urine with a recovery of 95-100% after 24 h. Literature reported, in some cases, 50% retention in the body. HMF was completely converted to two metabolites, which have been identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as 5-hydroxymethyl-2-furoic acid and N-(5-hydroxymethyl-2-furoyl)glycine. Administration of high doses of HMF showed a similar rapid elimination, but a proportional reduction of the amount of the glycine conjugate produced. Whole-animal-body autoradiography confirm that shortly after administration radioactive material was present in the liver but was mostly in the kidney and the bladder. The only significant difference between po and iv administration was the presence of a higher level of radioactive material in the brain of iv-treated rats.

Administration, Oral↗
PubMed1986

Urinary metabolites of caffeine in the premature infant.

Caffeine metabolites in urine from premature infants were analysed by TLC and HPLC. Caffeine, dimethyluric acids, mono- and dimethylxanthines and, for the first time, a uracil derivative (6-amino-5-[N-methylformylamino]-1,3-dimethyluracil) were identified.

Biotransformation↗
PubMed1986

1,3,8-Trimethylallantoin: a major caffeine metabolite formed by rat liver.

The formation of 1,3,8-trimethylallantoin from caffeine is demonstrated for the first time in vitro in rat liver slices. This compound constitutes 15% of total in vitro metabolites. With this identification, all the metabolic pathways of caffeine shown in vivo (N-demethylation, oxidation to uric acids and formation of uracil and allantoin derivatives) are demonstrated in vitro.

Allantoin↗
PubMed1985

High levels of methylxanthines in chocolate do not alter theobromine disposition.

Theobromine disposition was measured twice in 12 normal men, once after 14 days of abstention from all methylxanthines and once after 1 week of theobromine (6 mg/kg/day) in the form of dark chocolate. Mean theobromine t 1/2, apparent volume of distribution, and clearance after abstinence from all methylxanthines were 10.0 hours, 0.76 L/kg, and 0.88 ml/min/kg. High daily doses of chocolate for 1 week did not change these values. After subjects abstained from methylxanthines, urinary radioactivity over 72 hours after a single, oral dose of [8-14C]theobromine consisted of 42% 7-methylxanthine, 20% 3-methylxanthine, 18% theobromine, 10% 7-methyluric acid, and 10% 6-amino-5[N-methylformylamino]-1-methyluracil. A week of daily theobromine consumption in the form of dark chocolate also did not alter this urinary profile of theobromine and its metabolites. Although these results might appear to differ from other reports of inhibition of theobromine elimination after five consecutive daily doses of theobromine in aqueous suspensions, both the rate and extent of absorption of theobromine in chocolate were less than that of theobromine in solution. Relative bioavailability of theobromine in chocolate was 80% that of theobromine in solution. This reinforces the fundamental principle that both the metabolic and the therapeutic consequences of a particular chemical can differ when that chemical is given in the pure compared with the dietary form.

Administration, Oral↗
PubMed1985

Oxidation and metabolic effects of fructose or glucose ingested before exercise.

The aim of this study was to compare the effects of fructose (F) and glucose (G) intake before exercise on oxidation of the ingested substrate, glycogen utilization, work output, and metabolic changes. Ten trained subjects ingested F or G (1 g/kg), both of which were naturally enriched in 13C. After 1 h of rest, they exercised on an ergometer at 61% of their maximal oxygen uptake (VO2 max) for 45 min, which was immediately followed by 15 min at their maximal voluntary output. During the resting hour, blood insulin and glucose were lower (p less than 0.05) and respiratory quotient and blood lactate higher (p less than 0.01) after F. During exercise, the differences disappeared, apart from a transient but moderate (4.3 mmol/l) hypoglycemia after G compared to F. No difference between F and G was observed for uric acid, glycerol, FFA, and glucagon. Glycogen decrements in the vastus lateralis muscle were 67 +/- 9 (F) and 97 +/- 15 (G) mmol/kg, values not significantly different from each other (P greater than 0.05). The maximal voluntary work produced during the last 15 min did not differ between treatments. During the 2 h after sugar ingestion, 30 +/- 3 g of F and 26 +/- 3 g of G were oxidized to 13CO2. These findings indicate that fructose ingested before exercise was utilized at least as well as glucose, allowed a more stable glycemia, and did not modify performance.

Adult↗
PubMed1985

Contribution of 500 g naturally labeled 13C dextrin maltose to total carbohydrate utilization and the effect of the antecedent diet, in man.

Exogenous carbohydrate oxidation was studied for 24 h in 14 healthy young male volunteers after ingestion of 500 g naturally labeled 13C carbohydrate. Prior to the test, the antecedent diet was high in fat (4 subjects), mixed (4 subjects), or high in carbohydrate (6 subjects). The rate of exogenous carbohydrate oxidation was greater in the high carbohydrate and mixed diet groups than in the high fat group and endogenous carbohydrate continued to contribute to total carbohydrate oxidation for approximately 10 h after ingestion of the carbohydrate load in all groups. After 14 h, 178 +/- 5 g, 241 +/- 11 g and 260 +/- 9 g carbohydrate had been utilized of which 130 +/- 8 g, 155 +/- 6 g and 180 +/- 7 g was of exogenous origin in the high fat, mixed and high carbohydrate groups respectively. At the end of the test, postabsorptive glucose oxidation was of exogenous origin whatever the antecedent diet indicating that much of basal hepatic glucose production was covered by glycogenolysis of recently synthesized labeled glycogen.

Adult↗
PubMed1985

Whole body protein synthesis and energy expenditure in very low birth weight infants.

The aim of the present work was to study whole body protein synthesis and breakdown, as well as energy metabolism, in very low birth weight premature infants (less than 1500 g) during their rapid growth phase. Ten very low birth weight infants were studied during their first and second months of life. They received a mean energy intake of 114 kcal/kg X day and 3 g protein/kg X day as breast milk or milk formula. The average weight gain was 15 g/kg X day. The apparent energy digestibility was 88%, i.e. 99 kcal/kg X day. Their resting postprandial energy expenditure was 58 kcal/kg X day, indicating that 41 kcal/kg X day was retained. The apparent protein digestibility was 89%, i.e. 2.65 g/kg X day. Their rate of protein oxidation was 0.88 g/kg X day so that protein retention was 1.76 g/kg X day. There was a linear relationship between N retention and N intake (r = 0.78, p less than 0.001). The slope of the regression line indicates a net efficiency of N utilization of 67%. Estimates of body composition from the energy balance, coupled with N balance method, showed that 25% of the gain was fat and 75% was lean tissue. Whole body protein synthesis and breakdown were determined using repeated oral administration of 15N glycine for 60-72 h, and 15N enrichment in urinary urea was measured. Protein synthesis averaged 11.2 g/kg X day and protein breakdown 9.4 g/kg X day. Muscular protein breakdown, as estimated by 3-methylhistidine excretion, contributed to 12% of the total protein breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗