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Biomedical subjects

M Richelle

Publications and source records attributed to M Richelle.

At least 37 records · Page 2Linked to original sources

[Parenterally administered medium-chain triglyceride-induced changes in carnitine metabolism].

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate was studied in four healthy male adults. Glucose and amino acids were infused alone for three hours, then continued for another 5.5 hours together with a lipid emulsion containing only long-chain triglycerides or a mixture of medium-chain and long-chain triglycerides (50:50; w/w). During the fat-free infusion, the concentration of free carnitine rose, while the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 hours reduced free carnitine to lower values (32.4 +/- 4.7 mumols/L) than long-chain triglycerides infusion (44.4 +/- 2.7 mumols/L). By contrast, the plasma concentrations of short-chain acylcarnitines (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/L; p less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/L; p less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. These findings suggest that oxidation of medium-chain fatty acids is to some extent carnitine-dependent, whether or not transport into mitochondria is carnitine-mediated.

Adult↗

Stabilisation of plasma substrate concentrations: A model for conducting metabolic studies.

Metabolic studies involving changes in plasma substrate concentrations are frequently carried out after an overnight fast. This condition, however, is a transition between the post-prandial period and the beginning of starvation, and thus is associated with rapid changes in the plasma concentration of many substrates. Such alterations might interfere with the interpretation of modifications in plasma concentrations resulting from experimental manipulations. Infusion of glucose at a rate of 250 mg kg(-1) h(-1) for 1h and subsequently at 162 mg kg(-1) h(-1) together with amino-acids at 50 mg kg(-1) h(-1) is used to stabilise the plasma concentration of most substrates within 3 h, a condition which is maintained for the subsequent 5 h or more. This study offers a model which is more suitable for many metabolic investigations than overnight fasting and which takes little time or expense to prepare.

Journal Article↗

Behavioral models of memory and amnesia.

In modelling memory and amnesia, the different forms of cognition must be distinguished. For memory, distinctions between acquisition, storage, and retrieval must be made and the different kinds of memory (e.g., immediate, working, reference) identified. Other notions, such as attention, orientation, and vigilance also belong under the heading "cognition". Thus the term "cognition enhancer" is imprecise because it does not indicate which kind of cognition is to be enhanced. Animal models should be developed for each type of cognition, be based on information from the clinic, and attempt to be specific. Examples of models more specific than the passive avoidance test were discussed and included the radial maze, in which different kinds of memory could be analyzed and correlated with, for example, changes in central cholinergic activity. From the point of view of drug development an important distinction was made between "empirical" and "simulation" models. In other areas of psychopharmacology "empirical" models have been widely used because they show predictable responses to known reference compounds. In the field of cognition there are no generally recognized reference compounds and therefore no "empirical" models. There is therefore a need for "simulation" models which imitate the various aspects of cognition and its pathology. The major criterion for validating this kind of model is that it should show changes similar to those observed in humans either resulting from a particular pathology or from a particular drug treatment.

Amnesia↗

Medium-chain triglycerides induce alterations in carnitine metabolism.

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate were studied in four healthy male adults. Glucose and amino acids were infused alone for 3 h, then continued for another 5.5 h together with a lipid emulsion containing only long-chain triglycerides or a 50:50% (wt/wt) mixture of medium-chain and long-chain triglycerides. During the fat-free infusion, the concentration of free carnitine rose, whereas the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 h reduced free carnitine to lower values (32.4 +/- 4.7 mumols/l) than long-chain triglycerides infusion (44.4 +/- 2.7 mumol/l). By contrast, the plasma concentrations of short-chain acylcarnitine (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/l; P less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/l; P less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. This suggests that intravenous medium-chain triglycerides are not metabolized independently of carnitine. Carnitine may play an important role in removing acyl and acetyl groups from mitochondria and in restoring the intramitochondrial CoA level. Fat substrates are converted into compounds that might be utilized by tissues that do not normally oxidize fatty acids, creating an interorgan energy cycle.

3-Hydroxybutyric Acid↗

Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion.

Because 10% and 20% intravenously administered lipid emulsions (intralipid preparations) differ in their phospholipid/triglyceride ratio (0.12 and 0.06, respectively), 28 low birth weight infants requiring parenteral nutrition for at least 1 week were selected at random to receive either emulsion to determine the effects on plasma lipids and lipoproteins. Triglyceride intake was progressively increased to reach 2 gm/kg per day between days 4 and 7. During that period, all plasma lipids in samples taken 6 hours after infusion were higher in the 10% intralipid group. In comparison with day 0 values, triglyceride concentrations decreased (63 +/- 7 to 45 +/- 4 mg/dl; p less than 0.05) in the 20% group. Cholesterol levels increased in both groups, but the rise was more than twofold higher in the 10% group. Phospholipid increase was approximately 25% in the 20% group but more than 125% in patients receiving the 10% emulsion (p less than 0.005). The changes in plasma cholesterol and phospholipid levels were almost entirely in low-density lipoproteins. After 7 days, eight infants from each group were given the alternate emulsion, which resulted in a reversal of lipid patterns in each patient. We conclude that the higher phospholipid intake in 10% than in 20% intralipid is associated with higher plasma triglyceride concentrations and leads to accumulation of cholesterol and phospholipids in low-density lipoproteins. Emulsions with lower phospholipid content may be preferable for low birth weight infants and perhaps other patient populations with impaired removal of parenteral fat emulsions.

Cholesterol, HDL↗

Interactions between exogenous fat and plasma/lipoproteins.

Fat emulsions are essentially composed of triglycerides and phospholipids. Their elimination from the plasma--which is generally rapid--is influenced by the amount and the composition of both these components. During their short stay in the vascular compartment, exogenous particles undergo major compositional changes. They acquire various apolipoproteins--namely C-II, C-III, E and A-IV--by transfer from HDL. They also acquire esterified cholesterol from HDL and LDL and transfer exogenous triglycerides and phospholipids to these endogenous lipoproteins. These exchanges are affected by the type of triglyceride fatty acids and the amount of phospholipids present in fat emulsions, as well as by the infusion rate. Some 10% of emulsions--with a high phospholipid: triglyceride ratio--contain a huge phospholipid excess which can be isolated as a separate fraction from the triglyceride-rich particles. These phospholipids markedly interfere with the metabolism of cholesterol and the plasma lipoprotein profile.

Cholesterol↗

Low doses of pulsed ultrasound and chromosomal abnormalities in male mouse germ cells.

Male mice were exposed to pulsed ultrasound (intensity less than 1 mW, frequency 3.5 MHz) for 30 min or to sham treatment. After 30 h, 11, 12 or 13 days, the testes were cytologically and histologically examined (using squash preparations, air-drying and sections). The resulting damage was studied at diakinesis-metaphase I and II, spermatogonial metaphase and anaphase. The investigation by air-drying did not show any significant increase in chromosome damage, 30 h, 11, 12 and 13 days after treatment (spermatogonial and spermatocytic metaphases). There was, however, a significant increase of the frequency of aneuploid cells detected at metaphase II. Investigations by squash techniques or sections did not reveal adverse effects on the spindles at spermatogonial and spermatocytic anaphases. We suggest that the reduction of fertility previously observed in our clinic could be explained by an increase of aneuploidy if germ cells are exposed to ultrasound during diakinesis of the first meiotic division.

Anaphase↗

Control of key pecking by the duration of a visual stimulus.

Pigeons' key pecks were brought under the control of the duration of a visual stimulus in one-key and two-key procedures. In the one-key procedure, pecks were reinforced after presentations of a long-duration stimulus but not after presentations of a short-duration stimulus. In the two-key procedure, left-key pecks were reinforced after the long-duration stimulus and right-key pecks after the short-duration stimulus. In both procedures, the long-duration stimulus was 10 sec, and the short-duration stimulus was increased from 1 to 8 sec in 1-sec steps. Discriminative control developed with both procedures, but with greater accuracy in the two-key procedure, in which a difference threshold was obtained at short-duration values between 7 and 8 sec, or about 2.5 sec shorter than the long-duration stimulus.

Journal Article↗

Titration schedule with rats in a restraining device.

In a restraining device, providing a constant localization and easy placement of stimulating electrodes, rats were conditioned to push a front panel in order to reduce the intensity of a shock which otherwise increased regularly every 10 sec. Rapid conditioning was obtained from all subjects. They showed a very stable behavior, with negligible inter- or intra-individual variability throughout very long experimental sessions. The operant nature of the response was demonstrated further in extinction, where no shock was delivered, and in situations where the animal could not change the predetermined intensity of the shock. The interpretation of the obtained threshold was discussed with reference to previous studies on titration schedule. It was suggested that, with the parameters used, the shock intensity at which it was maintained by the rats' behavior, had the value of a warning signal, and that, in this particular case, the titration schedule generated mainly discriminative avoidance behavior rather than escape behavior.

Journal Article↗

Combined action of diazepam and d-amphetamine on fixed-interval performance in cats.

Cats trained under a fixed-interval 5-min schedule of milk presentation were injected with diazepam, amphetamine, and combinations of amphetamine and diazepam. Diazepam increased overall response rate as a function of the dose and disrupted the temporal pattern of responding. Low doses of amphetamine (0.5 mg/kg) usually increased the response rate; higher doses (1 to 2 mg/kg) either decreased the response rate or had little effect. Amphetamine always disrupted the temporal pattern of responding, even though it did not affect the overall rate. When doses of amphetamine that increased the response rate or left it unchanged were combined with diazepam, a potentiated increase in response rate occurred. When doses of amphetamine that decreased the response rate were combined with diazepam, the amphetamine-induced rate decreases were reversed at least partially. Less clear potentiation of disruption of the temporal pattern of responding was observed when amphetamine and diazepam were combined.

Animals↗