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Use of even-numbered carbon atom dicarboxylic salts in parenteral nutrition as fuel substrate
No full textSebacic acid (C10), a saturated, straight-chain dicarboxylic acid with 10 carbon atoms in disodic salt form, was given intravenously to two groups of healthy male volunteers in order to evaluate its possible use in total parenteral nutrition. The first group, composed of six subjects, received 1000 mg of sebacate as a bolus; six other subjects (second group) received 10 g of sebacate dissolved in 500 mL of double-distilled water at an infusion rate of 3.33 g/h over 3 hours. The serum sebacate data for each subject were analyzed by computer, using biexponential fit corresponding to a 2-compartment open model. The distribution half-life (t1/2) was 0.34 +/- 0.06 hour and the elimination phase was rather rapid (Ke = 2.10 +/- 0.38/h); the volume of the central compartment was 2.79 +/- 0.54 L and the volume of tissue compartment 3.72 +/- 0.14 L. These data showed a good tissue fixation of sebacate. The plasma clearance was evaluated to be 5.96 +/- 2.19 L/h and the renal clearance was 19.22 +/- 10.69 L/h, indicating that a tubular secretion of C10 takes place. The serum concentration of sebacate raised to the maximal value at the end of the infusion (180 minutes), corresponded to 480.50 +/- 43.02 micrograms/mL. Respiratory and metabolic parameters were evaluated by indirect calorimetry from the beginning of the infusion for 210 minutes. The O2 consumption (VO2 mL/min per square meter) remained essentially unchanged throughout the experiment (from 154.3 +/- 28.3 at 0 to 155.3 +/- 39.5 at time 180 minutes).(ABSTRACT TRUNCATED AT 250 WORDS
Toxicity of disodium sebacate
No full textInvestigations of the acute toxicity of disodium sebacate after oral, i.p. and i.v. administration were carried out on 220 Wistar rats (110 males and 110 females) and 204 New Zealand rabbits (102 males and 102 females). No oral acute toxicity was found. On the contrary LD50 +/- s.e. of 5500 +/- 830 mg/kg b.w. and 6000 +/- 850 mg/kg b.w. were found respectively for rats and rabbits after i.p. sebacate administration. When sebacate was given i.v., the median lethal dose +/- s.e. was 560 +/- 86.5 mg/kg b.w. for rats and 1400 +/- 267.2 mg/kg b.w. for rabbits. Similar results were obtained in corresponding groups of animals (in total 220 rats and 204 rabbits) given oral, i.p. and i.v. saline solutions with added glucose in order to obtain the same value of osmolarity and sodium ion concentration. The above results appear indicative of low toxicity of disodium sebacate, and suggest that the toxic effects found could be due to the sodium content of the compound administered. Similarly, subacute and chronic toxicity was investigated in forty rats and forty rabbits (twenty males and twenty females) fed disodium sebacate incorporated into pellets. When compared to the control animals, no significant differences in biological parameters (clinical, chemical and haematological values, growth curves and histological findings for the different organs) were observed in the test groups during the treatment period. In addition, fetal toxicity, teratogenicity and neonatal toxicity were investigated in twenty female rats and twenty female rabbits. Sebacic acid did not show any teratogenic effect and the development of the fetuses was regular
Short-term infusion of azelaic acid vs intralipid in healthy subjects evaluated by indirect calorimetry
No full textMedium-chain dicarboxylic acids (MCDA) are usually considered byproducts of beta-oxidation when omega-oxidizable medium-chain monocarboxylic acids are accumulated, as in beta-oxidation impairment. However, evidence exists of a mitochondrial and cytoplasmatic peroxisomal carnitine independent beta-oxidation of these diacids. Our purpose was to evaluate whether MCDA could be used as source of calories. The metabolic response to intravenous administration of azelaic acid (AA) vs Intralipid (IL) was evaluated in six healthy overnight fasting male volunteers who received an infusion of 10 g of AA over 80 min and as a control 10 g of IL. AA reached a peak concentration at 80 min, (589 +/- 61 micrograms/ml) and was rapidly cleared from plasma (82 +/- 5 micrograms/ml at 240 min). Respiratory and metabolic parameters were evaluated by indirect calorimetry from the beginning of the infusion for 240 min. In both groups the CO2 production (VCO2) remained unchanged with no significant change from basal values. The O2 consumption (VO2 ml/min/m2) increased over basal values reaching a peak at the end of the infusion in both groups (AA from 119.4 +/- 16.9 to 143.0 +/- 27.6; IL from 124.7 +/- 16.8 to 152.3 +/- 29.5). Respiratory quotient (RQ) consequently decreased significantly (AA from 0.85 +/- 0.06 to 0.76 +/- 0.06; IL from 0.89 +/- 0.06 to 0.78 +/- 0.03) and calories derived from lipids increased. Metabolic rate (MR kcal/hr/m2) showed a slight increase (AA from 34.0 +/- 4.4 to 40.3 +/- 6.8; IL from 35.9 +/- 5.1 to 41.3 +/- 10.5). There was no significant difference between AA and IL treatment in all measurements.(ABSTRACT TRUNCATED AT 250 WORDS
Temporal patterns of C-reactive protein and other acute phase proteins after kidney transplantation
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Tissue uptake and oxidation of disodium sebacate in man
No full textIn order to better ascertain its possible use as an alternative fuel substrate in total parenteral nutrition, sebacate (Sb) metabolism was studied in seven overnight-fasting healthy male volunteers, who received a constant iv infusion (99 mmoles over 8 hours) of disodium sebacate. Sb oxidation rate was determined using an isotopic sebacate (disodic salt of (1-10)14C-sebacic acid) infusion (100 mu Ci from the fourth to the eighth hour of the cold sebacate infusion). Blood samples were collected during and after sebacate infusion at intervals of 30 minutes and Sb serum concentrations were determined by high performance liquid chromatography. Excreted radioactivity (mu Ci/min) was measured by bubbling the expired air into an apparatus containing 3 mEq hyamine to trap CO2 from a 20-L Douglas-bag. CO2 production and O2 consumption were measured before and at 4 and 8 hours after starting the infusion. Twenty-four hour nitrogen excretion with urine was obtained. The RQ and the percent of calories derived from lipid oxidation were calculated by indirect calorimetry. The Sb serum level at the plateau phase was (mean +/- SD) 4.54 +/- 0.71 mumole/mL, the overall rate of tissue uptake was 180.89 +/- 4.50 mumole/min, and the percent oxidation was 6.14 +/- 0.44%. At the end of Sb infusion the RQ dropped to 0.839 +/- 0.043, the percent of calories due to sebacate oxidation was 1.59 +/- 0.52%, and the calories derived from lipids increased to 37.77 +/- 12.90%. These data show that a definite amount of the sebacate infused is oxidized in human tissues
An 18-year-old woman with familial chylomicronaemia who would not stick to a diet
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Infections of the peritoneum including pancreas, mediastinum, pleura, wounds, and urinary tract.
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