Effects of ganglionic blocking drugs on blood glucose, amino acids, free fatty acids, free fatty acids and catecholamines at exercise in man.
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We compared intermittent (8 hours/day) versus continuous (24 hours/day) isocaloric lipid infusion regimens in 28 neonates. The lipid dose was increased incrementally by 0.5 gm/kg/day to either 3 gm/kg/day or until fat contributed 40% of daily calories. Serum total triglycerides, free fatty acids, free fatty acids/albumin molar ratio, and total cholesterol levels were measured prior to the daily lipid infusion, at the end of the intermittent infusion, and at 8 hours during the continuous infusion. Neonates less than 32 weeks postconception had significant fluctuation of triglycerides, free fatty acids, and free fatty acids/albumin molar ratio during the intermittent regimen at all lipid doses, but not during the continuous regimen. Neonates greater than or equal to 32 weeks postconception had significant fluctuation of serum triglycerides, free fatty acids, and free fatty acids/albumin molar ratio during the intermittent regimen with a lipid dose greater than or equal to 2 gm/kg/day, but not during the continuous regimen at all lipid doses. Serum free fatty acids correlated closely with serum triglycerides during both regimens (r = 0.89, P less than 0.001). Serum total cholesterol rose with increasing lipid doses during both regimens (f = 8.16, P less than 0.05). We conclude that neonates less than 32 weeks postconception tolerate the continuous regimen better than the intermittent regimen at all lipid doses; neonates greater than or equal to 32 weeks postconception tolerate both regimens well at lipid dose less than 2 gm/kg/day, but tolerate a continuous regimen better with lipid dose greater than or equal to 2 gm/kg/day.
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Free fatty acids accumulate in plant membranes after exposure of plants to environmental stress, such as freezing and desiccation. Fatty acid accumulation has been linked to various biophysical changes and to the occurrence of lipid peroxidation, but the relationships appear complex and inconsistent. The interactions between oxygen free radicals, free fatty acids and lipid peroxidation in plant membranes were examined further by studying peroxidation reactions in a model membrane system composed of a complex mixture of plant phospholipids, including various free fatty acids. Multilamellar liposomes were treated with oxygen free radicals generated from iron ascorbate. Increased concentrations of free palmitic acid up to 10 mol% (fatty acid/phospholipid) reduced the production of aldehydes detected by the thiobarbituric acid assay, but enhanced the production of fluorescent products. By contrast, increased concentrations of free linolenic acid increased aldehyde production and reduced the formation of fluorescent products. The two free fatty acids both enhanced the susceptibility of phospholipids to degradation as shown by the reduced recovery of esterified polyunsaturated fatty acids (linoleic and linolenic). The free radical reactions with or without free fatty acid additions catalyzed the selective degradation of phospholipids in the order phosphatidylethanolamine > phosphatidylcholine > phosphatidylinositol > phosphatidylglycerol. Selective degradation of phospholipids is often observed after periods of environmental stress or during senescence of plants, and has been cited as evidence for the involvement of phospholipases in these degenerative processes. The results indicate that selectivity is not a criterion for eliminating the involvement of oxygen free radicals in these degenerative processes. Furthermore, the results suggest that modifications of lipid composition during a plant's acclimation to adverse environments may determine the types of free radical reactions that occur due to stress.
This investigation evaluates the effect of prolonged glucose infusion on triglycerides and the composition in total serum fatty acids and free fatty acids in the rat. Glucose infusion over a period of 4 days leads to the following changes: serum triglyceride concentrations are two to three times elevated and serum insulin levels rise 10 times after 12 hours, followed by a steady decrease. Chain elongation is depressed in serum free fatty acids and even more in total serum fatty acids. In serum free fatty acids monodesaturation is unaltered whereas it is highly stimulated in total serum fatty acids. These alterations correlate with the changes of hepatic total fatty acids and do not correlate with changes of fatty acids from epididymal fat pads. The alterations reflect a specific carbohydrate-induced effect on hepatic fatty acid desaturation and chain elongation. They do not support the idea that serum free fatty acids are mainly secreted from the storage pool of adipose tissue; yet, they may have been newly synthesized in fat cells or even in the liver.
An accurate capillary gas chromatographic method using different internal standards for determining free fatty acids, cholesterol, cholesteryl esters, and triacylglycerols in plasma and other biological sources is described. It is designed to give information about species composition and, consequently, more detailed information about changes in lipid metabolism of patients suffering from metabolic disorders. After plasma extraction the lipids, except phospholipids, are directly examined without any further derivatization. For free fatty acid determination the programmed temperature vaporizer (PTV) injector was heated from 40 degrees C (sample introduction) to 190 degrees C. In a second gas chromatographic run the PTV-injector system was heated from 60 degrees C (sample introduction) to 400 degrees C, enabling the determination of free cholesterol, cholesteryl esters, and triacylglycerol species, differing in the number of carbon atoms. Evaluation of the values obtained resulted in coefficients of variation (%) of 1.0-2.8, 2.0, 1.29-2.24, and 2.8, for free fatty acid standards, plasma free fatty acids, cholesterol and cholesteryl ester standards, and plasma total cholesterol, respectively. Free fatty acids, cholesterol, and cholesteryl esters were not influenced by storage of plasma at -24 degrees C up to 4 days prior to extraction. The results of the gas chromatographic method and the enzymatic methods correlated well. Determination by gas chromatography yielded higher total cholesterol and lower triacylglycerol values than those values obtained by enzymatic methods.
Free fatty acids (FFAs) are not only an important direct source of energy but they also play key roles in regulating a range of physiological responses. Although it was long assumed that such effects of FFAs must occur following cellular uptake, and potentially via their conversion to fatty acyl-CoAs, it is now apparent that FFAs also function directly as agonists at a number of G protein-coupled receptors (GPCRs). Tissue distribution studies and, subsequently, siRNA knock-down experiments have indicated key roles for these GPCRs in glucose homeostasis, adipogenesis, white cell recruitment and potentially in a range of other processes. Considerable interest is thus now centred on the generation of potent and selective small molecule ligands, both as tool compounds to further unravel the biology and physiological role of this group of GPCRs and as starting points for possible therapeutic intervention in a range of areas, particularly those associated with 'metabolic syndrome'.
Free fatty acids (FFA), the uranyl ion, and the basic dye Rhodamine B form colored complexes, which are extractable into toluene or benzene. Fatty acids of different chain lengths above C(10) and different degrees of unsaturation gave constant molar yield. Complexes in toluene alone are unstable, especially in the light, but a small amount of aqueous uranyl acetate stabilizes them sufficiently for determination. At constant uranyl and Rhodamine B concentrations, a plot of optical density vs. FFA concentration yields two straight lines of different slope, i.e., a biphasic standard curve. Phospholipids interfere, and must be removed with zeolite during FFA extraction. Recovery of FFA added to rat plasma was very similar to that with titration. Assay of rat and dog plasma samples under fasting and fed conditions gave good agreement with the titration method. Values of human plasma samples tended to be higher by the colorimetric procedure; a few samples gave significant disagreement. The method compares well with previous methods in sensitivity and accuracy, and offers advantages in speed, simplicity, and possibly specificity.
The effect of nicotinic acid on regional myocardial blood flow, percentage of segment shortening and myocardial uptake of free-fatty acids during a 15-min occlusion of the left anterior descending coronary artery and 3-hr reperfusion period was compared to a saline-treated control group. Nicotinic acid (2.4 mumol/kg/min i.v.) was infused 30 min before and throughout the occlusion period. Heart rate, arterial blood pressure and left ventricular systolic and end diastolic pressures were not different during occlusion and reperfusion in the nicotinic acid or saline-treated groups. However, left ventricular dP/dt, an index of global myocardial function and percentage of segment shortening in the ischemic region were greater during occlusion and reperfusion after nicotinic acid. Even though myocardial blood flow was unaltered in the normal or ischemic region during nicotinic acid infusion, subendocardial blood flow during reperfusion was enhanced significantly when compared to the control group. Nicotinic acid also decreased free-fatty acid uptake by the heart during occlusion which returned gradually to the pretreatment control during 3 hr of reperfusion. Thus, the improvement in percentage of segment shortening, dP/dt and subendocardial blood flow during reperfusion may be related to the ability of nicotinic acid to reduce free-fatty acid uptake by the heart during coronary occlusion.
Nutrition experiments with various levels of calorie and protein intake were carried out on five healthy young men. Three series of experiments with two persons each were undertaken for periods up to 14 days. The first part of each experiment, with 1100 to 1500 kcal/day, was immediately followed by the second part, with 3500 to 2300 kcal/day. The concentrations of insulin, free fatty acids, glucose and amino acids were determined in the morning, fasted blood. The nitrogen balance was also determined. When insufficient carbohydrate intake is coupled with normal and high protein content of the food, there is interindividually an initial drop in the insulin concentration. Regardless of the absolute insulin concentration, this drop causes an increase in the free fatty acids and the branched-chain amino acids, together with a decrease in the concentrations of alanine and glycine (threonine) in the blood and a negative nitrogen balance. The high concentrations of branched-chain amino acids and the low threonine concentrations might be involved as feedback regulators in the further regulation of the gluconeogenic metabolism. When carbohydrate calories are added to the diet, a simultaneous decrease in the free fatty acids and branched-chain amino acids and increase in the blood concentrations of insulin, alanine, glycine and threonine within 24 to 48 h are only observed with 3500 kcal/day and 0.8 to 1.4 g protein per kg body weight. A positive nitrogen balance, however, is only observed with 1.4 g protein per kg body weight, regardless of the relative changes in the insulin level, while the increase in alanine and decrease in branched-chain amino acids (valine) are greatest at 0.8 g protein per kg body weight and day. In spite of the high glucose level, the falling insulin level provokes counter-regulatory processes in which the low concentrations of branched-chain amino acids and the high threonine (alanine) concentrations may play a role.
The disappearance rate of plasma. free glycerol, free fatty acids and triglycerides following the termination of short-term (6-hr) infusion of fat emulsion (Intralipid) was studied in 12 low-birth-weight infants. The mean K values for each lipid component were found to be higher in infants receiving 10% glucose. Owing to the wide individual variation of responses and the small number of infants studied, only the disappearance rate of free fatty acids reached the level of significance. It is concluded that increased amounts of glucose given simultaneously with fat emulsion could diminish hyperlipidaemia by increasing the clearance of lipids from the plasma.
The manner in which arachidonic acid and other free fatty acids influence the vesicular uptake of glutamate and gamma-aminobutyric acid (GABA) has been investigated. The cis-polyunsaturated fatty acid arachidonic acid (20:4), eicosapentanoic acid (20:5) and linolenic acid (18:3) at 150 nmol/mg protein (50 microM) inhibited the vesicular uptake of glutamate and GABA more than 70%. Reduced inhibition of vesicular uptake was seen with the cis-monounsaturated fatty acid oleic acid (18:1) and the trans-mono-unsaturated fatty acid elaidic acid (18:1). The saturated fatty acids stearic acid (16:0) and arachidic acid (20:0) had no significant effect on the uptake. The inhibition of vesicular uptake by arachidonic acid was prevented by the addition of fatty acid free bovine serum albumin. Arachidonic acid inhibited in a dose-dependent manner the generation of the transmembrane pH gradient of the synaptic vesicles. This inhibition was proportional to the inhibition of the vesicular uptake of glutamate and GABA. The saturated fatty acid arachidic acid showed no inhibition of delta pH generation. Arachidonic acid at 200 nmol/mg of protein did not increase the uptake-independent leakage of glutamate and GABA from the vesicles, showing that the effect of arachidonic acid is not caused by an unspecific detergent effect. These results suggest that arachidonic acid and other polyunsaturated fatty acids are acting like proton-ionophores on the vesicular uptake of these neurotransmitters. This finding may have implications for the increased fatty acid concentration during pathological conditions like ischemia and in long term potentiation.
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This paper discusses a rapid GC-FID technique for the simultaneous quantitative analysis of FFA, MAG, DAG, TAG, sterols, and squalene in vegetable oils, with special reference to palm oil. The FFA content determined had a lower SE compared with a conventional titrimetric method. Squalene and individual sterols, consisting of beta-sitosterol, stigmasterol, campesterol, and cholesterol, were accurately quantified without any losses. This was achieved through elimination of tedious conventional sample pretreatments, such as saponification and preparative TLC. With this technique, the separation of individual MAG, consisting of 16:0, 18:0, and 18:1 FA, and the DAG species, consisting of the 1,2(2,3)- and 1,3-positions, was sufficient to enable their quantification. This technique enabled the TAG to be determined according to their carbon numbers in the range of C44 to C56. Comparisons were made with conventional methods, and the results were in good agreement with those reported in the literature.
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