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Biomedical subjects

A C Bach

Publications and source records attributed to A C Bach.

33 records · Page 2Linked to original sources

Two-dimensional NMR studies of the antimicrobial peptide NP-5.

Nearly complete proton resonance assignment of the rabbit antimicrobial peptide NP-5 has been made from two-dimensional NMR data taken at a single temperature. The assignment procedure involved acquisition of phase-sensitive double-quantum-filtered correlation spectra, relayed coherence-transfer spectra, total correlation (homonuclear Hartmann-Hahn) spectra, double- and triple-quantum spectra, and nuclear Overhauser effect spectra. The combination of these complementary experiments simplified and accelerated resonance assignment of the peptide. Individual assignments were made at 20 degrees C for all amide and C alpha protons in the peptide, and for all nonlabile side-chain protons on 26 of the 33 amino acid residues in NP-5. Analysis of the proton-proton nuclear Overhauser effect connectivities, the slowly exchanging amide protons, and the proton chemical shifts in NP-5 indicates that the peptide has a stable, ordered structure in solution. These data also indicate that residues 19-29 in NP-5 are involved in an antiparallel beta-sheet that has a hairpin conformation.

Amino Acid Sequence↗

Metabolic effects of high-protein diets in Zucker rats.

The effects of dietary protein on the metabolism of proteins, carbohydrates, and especially, lipids were investigated in genetically obese Zucker rats and their lean siblings. For 40 days the rats received diets containing 15%, 64%, or 82% protein, included at the expense of cornstarch. In the obese animals, the high-protein diets led to decreased food intake and weight gain. While these diets decreased the activities of lipogenic enzymes along with the lipid gain, they did not decrease the final body-fat content. The increase protein intake stimulated hepatic ureogenesis and gluconeogenesis. Lipolysis was stimulated, as demonstrated by an accumulation of ketone bodies in the liver. Blood levels of triacylglycerols, free glycerol, and nonesterified fatty acids were concomitantly decreased, which suggests an accelerated turnover of lipids. Whatever the composition of the diet, total energy retention of the lean rats was always less than that of the obese rats. The changes observed on high-protein diets were essentially the same for the two groups, except that the final body-content of lipids in the lean rats was significantly lower. In the absence of exogenous carbohydrate, the lean rats were barely able to retain nitrogen and to maintain hepatic lipogenesis. Unlike the rats from other strains, the lean Zucker rats could not adapt to a low-carbohydrate diet; this failure may be due to a metabolic disorder.

Acetyl-CoA Carboxylase↗

Metabolic effects of medium- or long-chain triglycerides and high-protein, carbohydrate-free diets in Zucker rats.

The effects of protein levels and types of fat in the diet on the metabolism of lean and obese Zucker rats were studied. For 40 days the rats were fed ad libitum one of four diets: two "usual protein" diets (19% protein by weight) with 19.4% triacylglycerols, either long chain (UP-LCT diet) or medium chain (UP-MCT diet); and two high protein (64% protein), carbohydrate-free diets, again with 19.4% triacylglycerols (HP-LCT and HP-MCT diets, respectively). The energy intakes of the obese rats decreased about equally on the HP-LCT, UP-MCT, and HP-MCT diets. The daily weight gain, which was high in the UP-LCT rats, was lower when carbohydrates were replaced by proteins, or when LCTs were replaced by MCTs; furthermore, when these two changes were made together, their beneficial effects on body weight were additive. The lipid gain, too, was high with the UP-LCT diet and lower both with the high protein diets and with the MCT diets; again combining the two amplified the two individual effects, so much that the final lipid concentration in the body was lowered, whereas the concentration of water increased. Hepatic acetyl CoA carboxylase activity was low when the diet supplied plenty of LCTs, but replacing carbohydrates with proteins in such a diet produced an additional decrease in this enzymatic activity. When either a normal protein or a high protein diet supplied MCTs in place of LCTs, acetyl CoA carboxylase activity was high and similar to that found with a high carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Plasma carnitine in women. Effects of the menstrual cycle and of oral contraceptives.

The plasma concentrations of carnitine were determined in a group of 35 women and 35 men admitted to a clinic, and in another group of 18 women during their menstrual cycle. The values found for the women (45.1 +/- 2.6 nmol/ml of free carnitine and 59.1 +/- 2.8 nmol/ml of total carnitine) were not significantly different from the values obtained in men (respectively 42.4 +/- 1.7 and 55.5 +/- 1.9 nmol/ml). No direct relationship between the free or total carnitine concentrations and the concentrations of circulating lipids could be demonstrated. During the menstrual cycle the plasma concentrations of free and total carnitine remained unchanged. Intake of oral contraceptives caused an elevation in blood triacylglycerols and decreases in the levels of luteinizing hormone, follicle-stimulating hormone, and free and total carnitine.

Adult↗

Carnitine in human nutrition.

The oxidation of long-chain fatty acids is carnitine-dependent. Indeed, only when they are bound to carnitine, in the form of acyl-carnitines, do fatty acids penetrate into the mitochondria to be oxidized. To meet the need for carnitine, animals depend on both endogenous synthesis and an exogenous supply. A diet rich in meat supplies a lot of carnitine, while vegetables, fruits, and grains furnish relatively little. Although it has a low molecular weight and acts at low doses in a vital metabolic pathway, carnitine should not be considered a vitamin, but rather a nutritive substance. Indeed, it seems that the diet of the adult human need not necessarily furnish carnitine: the healthy organism, given a balanced nutrition (sufficiently rich in lysine and methionine), may well be able to meet all its needs. Furthermore, it seems that a reduction of the exogenous supply of carnitine results in a lowering of its elimination in the urine. However, dietary carnitine is more important during the neonatal period. The transition from fetal to extrauterine life is accompanied by an increased role of lipids in meeting energy needs. This change is accompanied by a rise in the body of the levels of carnitine, which is mainly supplied in the maternal milk. Finally, this review briefly surveys the illnesses in which a dietary carnitine supplement proves useful.

Animals↗

Medium-chain triglycerides: an update.

A review of the literature on the medical and nutritional use of medium-chain triglycerides (MCTs) since 1970 is presented with additional discussions on the various modifications and applications of the MCTs in the synthesis of certain structured lipids. The metabolism of MCTs in the liver and extrahepatic tissues is discussed along with further documentation of the use of MCTs in malabsorption and hyperlipidemia cases. Recent applications of MCTs and modified MCTs in hyperalimentation, deficiency in the carnitine system, epilepsy, obesity, and other special areas of application are cited. The use of medium-chain monodiglycerides for dissolving cholesterol gallstones is presented. The contraindications for the use of MCTs in ketosis, acidosis, and cirrhosis are also discussed. Suggestions for use of MCTs in a variety of medical and nutritional applications are presented.

Animals↗

Gram-positive bacterial sepsis in rat and tissue lipolytic activity on commercial parenteral fat emulsions.

To study the influence of a gram-positive sepsis on the metabolism of circulating lipids, fasted rats were injected with saline (control group) or with a suspension of heat-killed or live Staphylococcus aureus. 18 h later, body temperature was increased, while albuminemia and ketonemia were decreased in the group injected with heat-killed bacteria, as opposed to the control group. Passing from these groups to the group injected with live bacteria, more differences appeared: increase of triglyceridemia and free cholesterolemia; decrease of esterified cholesterol levels and especially of the in vitro activity of diaphragm, heart and adipose tissue lipoprotein lipase and of hepatic lipase. The decrease of lipolytic activities occurred whether they were measured on a fat emulsion containing long-chain or medium- and long-chain triglycerides. The fact that for the latter the activity was always higher than for the former suggests that the host infected with gram-positive bacteria would clear exogenous fat more easily in the case of medium-chain triglycerides.

Animals↗

Intralipid 10%: physicochemical characterization.

OBJECTIVES: Parenteral fat emulsions contain two populations of particles: artificial chylomicrons rich in triacylglycerols (TAG), and liposomes (bilayer of phospholipids [PL] enveloping an aqueous phase). Centrifugation permits isolating the liposomes in the infranatant called mesophase. The aim of the present work was to better characterize this mesophase chemically and to view the particles it contains by electron microscopy. METHODS: Electron microscopy (Philips 410) was performed after cryofracture on native 10% Intralipid, mesophase (centrifugation for 1 h at 27 000 g), and a liposome-enriched fraction (ring of density 1.010-1.030 g/l obtained after centrifuging mesophase in a KBr density gradient at 100 000 g for 24 h). The TAG and protein content of the mesophase was analyzed and the proteins partially characterized by immunodetection (Western-blot). RESULTS: This electron microscope study of 10% Intralipid gives evidence for the coexistence of artificial chylomicrons (mean diameter, 260 nm) and liposomes (43 nm), the latter being smaller than expected and containing 8% w/w TAG after purification. The solubilization of TAG in PL bilayers (reported to be < or = 3.1% w/w) might have been increased in parenteral emulsions by the manufacturing process or/and the high TAG/PL ratio. Minute amounts of proteins have also been detected and partially characterized using a specific antibody raised against the human 7 kDa Anionic Polypeptide Factor (APF), known to strongly interact with PL in bile. CONCLUSIONS: This work has shown that the size (mean diameter, 43 nm) of the liposomes present in 10% Intralipid is smaller than that usually assumed. Traces of hydrophobic proteins in the emulsion may account for certain allergic reactions sometimes observed in infused patients.

Blotting, Western↗

Studies on the tolerance of medium chain triglycerides in dogs.

Two groups of five conscious dogs received total parenteral nutrition (about 100 kcal/kg body weight per 24 hr) continuously for 96 hr (0.28 g triglycerides/kg body weight per hr, constituting more than 55% of the energy supply). The only difference between the two groups was the nature of the 20% lipid emulsion. In one group, this emulsion contained only long-chain triglycerides (LCTs), and in the other it contained a mixture (vol/vol) of medium chain triglycerides (MCTs) and LCTs. MCTs thus were given in an amount of about 30% of the total energy supplied. During infusion with the MCT/LCT mixture, C8, C10, and C12 fatty acids appeared in the total plasma fatty acids. When the infusion was stopped, the medium-chain fatty acids disappeared; those with shorter chains did so more rapidly. The plasma triglyceride clearance was faster for the MCT/LCT mixture than for the LCTs, whereas phospholipid and cholesterol clearance seemed slower for the MCT/LCT mixture. With this mixture, there was a slight increase in the plasma concentrations of ketone bodies, lactate, and pyruvate, and a slight decrease in plasma glucose. The MCT/LCT mixture was well tolerated, causing no discernible problems, and, in particular, no signs of narcosis or encephalopathy.

Animals↗

Effects of L-carnitine infusion on intralipid clearance and utilization. Study carried out in septic patients of an intensive care unit.

Endogenous and exogenous supplies of carnitine are decreased in septic patients under total parenteral nutrition, while carnitine urinary elimination is increased. But the increase of lipid role in the energetic cover requires a greater intervening role of tissue carnitine. So one may hope that in septic patients additional supply of L-carnitine would increase the catabolism of infused lipids. Twenty-eight septic patients, admitted in an intensive care unit were given parenteral nutrition (200 g of glucose, 12.5 g of N/24 hr). On the day of the study, 250 ml of Intralipid 20% (Kabi Vitrum) were administered in 4 hr. During the same period 13 patients were infused with 2 g of L-carnitine (Sigma-Tau). The remaining 15 patients constituted the control group. Basic plasma levels of triglycerides, nonesterified fatty acids, free glycerol, phospholipids, and ketone bodies remained within physiological limits. They increased during the lipid infusion and returned to initial values, 4 hr after the end of the infusion. Free and total carnitine levels and free/total carnitine ratio were comparable to healthy subjects' reference values. These parameters increased during L-carnitine infusion. This infusion had no effect on exogenous lipid clearance. However, it seemed to increase the uptake and the hepatic oxidation of circulating fatty acids. It invalidated the increase of lactate and pyruvate that had been noticed when lipids were solely infused.

Adult↗

Medium-chain triglyceride-based fat emulsions: an alternative energy supply in stress and sepsis.

Medium-chain triglycerides (MCTs) and medium-chain fatty acids (MCFAs) have special physicochemical properties such as small molecular weight, small interfacial tension against water, and for the fatty acids, solubility in biological fluids. As a result the metabolic pathways followed by these fats in an organism are different and simpler, or identical but more rapid, than those followed by long-chain triglycerides (LCTs) and long-chain fatty acids (LCFAs). Consequently the MCTs have found numerous applications in oral or enteral nutrition and, more recently, in parenteral nutrition. The infusion of conventional fat emulsions in stress and sepsis is still controversial. A main question is whether an MCT supply can be beneficial for these patients. In this review, we will discuss different aspects of modified lipid and protein metabolism: exchanges between exogenous fat particles and lipoproteins; exogenous fat clearance, storage, and oxidation; reticuloendothelial system function; nitrogen balance; and hepatic function. For each of these perturbations, the MCT/LCT and structured lipid emulsions are theoretically capable to provide an appropriate solution. The efficiency of these emulsions has been demonstrated experimentally on animal models of stress and sepsis. However, the value of MCT-based fat emulsions for these pathological states has still to be ascertained by clinical studies.

Animals↗

Decreased lipolytic activity in tissues during infectious and inflammatory stress.

The clearance rate of endogenous and exogenous circulating lipids during the septic or inflammatory state remains a controversial subject. Thus, we have developed rat models of gram-negative and gram-positive sepsis and of sterile inflammation to study this problem. In addition to the febrile response, these stresses induced some of the following metabolic changes in the blood: decreased total protein, albumin, and ketone body levels and increased lactate, pyruvate, alanine, cholesterol, and triacylglycerol levels. The activities of heart, diaphragm, and adipose tissue lipoprotein lipase and of hepatic lipase decreased to differing extents depending on whether the enzyme substrate was a long-chain or a medium- and long-chain triglyceride-based emulsion. However, the latter emulsion was always hydrolyzed faster than the former. This observation suggests that, during infection/inflammation, the medium- and long-chain triglyceride-based emulsion would be cleared more quickly, would induce less hypertriglyceridemia, and would thus deliver lipid energy more rapidly than a traditional long-chain triglyceride-based emulsion.

Alanine↗

In vivo and in vitro release of lipoprotein lipase and hepatic lipase by low molecular weight heparins.

The purpose of this study was to compare lipoprotein lipase (LPL) and hepatic lipase (HL) releasing activities of different low molecular weight heparins (LMWH) and of a standard heparin. In vivo, the injection of most LMWH led to a LPL and HL releasing activity inferior to that obtained with a standard heparin. The releasing of LPL by muscle in vitro and of HL by perfused liver was identical with both types of heparins, but in epididymal adipose tissue, LPL activity released by LMWH was generally higher than the activity released by unfractionated heparin. We have no explanation for this apparent contradiction between the in vivo and in vitro results.

Adipose Tissue↗

Free and total carnitine in human serum after oral ingestion of L-carnitine.

Twelve students with in apparent good health and fasting since the previous evening ingested 2 g of L-carnitine on one day and a placebo on another day in a single-blind trial. Six blood samples were taken during the 24 h following the ingestion. Their blood carnitine levels increased (the free form by 81%, and the total by 57%) to a maximum at about 3.5 h and then slowly decreased. Twenty-four hours after ingestion, blood carnitine concentrations had still not returned to their initial levels. In the time interval where the decay curve approximated a single exponential, the half-life of the carnitine appeared to be of the order of 15 h. During the 24 h after the administration of the 2 g of L-carnitine, 7% +/- 1% of it was eliminated in the urine. This work suggest that the daily administration during a long period, of 2 g of L-carnitine guarantee in a healthy subject blood carnitine concentrations superior to the normal levels. Its remains to determine if the dose is sufficient in the case where L-carnitine is given to ameliorate a primary or secondary lack of carnitine, or to lower a high level of lipids in blood.

Administration, Oral↗