Infusion Of Triglyceride Emulsion Research Articles

The Cancer Patient Drowns in the Waves of Homeostatic Disorder

Neoplastic cells are formed as a result of reprogramming the gene expression. It is only when these cells are classified as non-local by the normal cells that confrontation occurs, and thus cancer begins as a disease. The tumorogenic degradation of the skeletal muscle plays a highly important role in the pathomechanism of the disease. It transforms a diminishing differentiation into an increasing homeostatic disorder, and is forced to provide energy to the malignant cells. This characterizes the completed form of the pathomechanism. Blocking the pathomechanism is the goal of a therapy that can be realized on two levels: At the level of reprogramming of the gene expression, which initiates the formation of neoplastic cells, a “reprogramming” of the reprogramming of gene expression could be achieved by altering the genomic flow of information. Increased anabolism (corresponding to the nutrient surplus) as well as increased catabolism (corresponding to nutrient) could lead to respective changes of the flows of genomic information. These opposing flows in a patient could be expected to result in interference or a shearing effect. Patients with acromegaly exhibit a 9.25% increased neoplasia prevalence, whilst patients with hyperthyroidism have 8.41% increased neoplasia prevalence. Patients with acromegaly and hyperthyroidism have a lower prevalence of neoplasia of 3.30%, i.e. the chance of these patients not contracting cancer is three times greater than patients with either only acromegaly or only hyperthyroidism. At the level of tumorogenic degradation of skeletal muscle, inhibition of muscle degradation by means of hypertriglyceridemia results in a significant prolongation of the life of carcinoma patients. This is based on the fact that inhibition of muscle degradation occurs after infusion of triglyceride emulsion. In the case of S. sanguinis bacteremia, there may be an interaction between enzymes from S. sanguinis, from the digestive tract and from the tumor. The source of infection determines the inactivation of the tumor enzyme and thus suppresses tumor development.

Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway.

Very low density lipoproteins (VLDL) are produced in the liver and contain apolipoprotein (apo) B-100 and endogenous lipids. By contrast, ingestion of fat leads to formation of chylomicrons containing apoB-48 secreted from the intestine. In this study, a 60-min intravenous infusion of a chylomicron-like triglyceride emulsion was given to healthy young men to examine whether competition between chylomicrons and VLDL for the same lipolytic pathway explains the increase in VLDL seen after meals. The responses of two major VLDL subfractions were determined by measuring the concentrations of apoB-100 in fractions of triglyceride-rich lipoproteins with Svedberg flotation rates of 60-400 (large VLDL) and 20-60 (small VLDL) that were separated from plasma by density gradient ultracentrifugation. A threefold elevation in plasma triglycerides was observed during the infusion together with a consistent linear increase of large VLDL. The rate at which large VLDL accumulated in plasma differed markedly among individuals and was not enhanced by doubling of the infusion rate. The response of small VLDL was more heterogeneous; however, a decrease was seen in most subjects. The combined pattern for the two VLDL species is what would be expected if large VLDL particles are the precursors of smaller VLDL species and if lipolysis of large VLDL is inhibited through competition from the triglyceride emulsion. The extent to which the triglyceride emulsion inhibited the lipolysis of VLDL and/or influenced the synthesis rate of large VLDL was estimated from simultaneous stable isotope studies. The emulsion caused a 75-90% block of the conversion of large VLDL apoB to small VLDL apoB and there was no sign of enhanced synthesis of large VLDL after infusion of the triglyceride emulsion. The corollary of these findings is that chylomicrons and their remnants impede the normal lipolytic degradation of VLDL and could thereby be indirectly implicated in the generation of atherogenic remnant lipoproteins.

Lymph Chylomicron Size is Modified by Fat Saturation in Rats

Mesenteric lymph chylomicrons were characterized during and after the establishment of steady-state triglyceride transport. Chylomicrons were isolated from lymph at 0, 2, 4, 6, 8 and 12 h after the start of an 8-h infusion of triglyceride emulsion (prepared using either corn or butter oil) at 160 μmol/(kg·h). Lymph flow was not influenced by triglyceride source. Output of triglyceride, measured both in whole lymph and in the chylomicron fraction, was not significantly affected by triglyceride source. Butter oil infusion produced a higher output of chylomicron phospholipid and unesterified cholesterol than was observed in response to corn oil emulsion. Ratios of transported phospholipid to triglyceride for butter oil chylomicrons were higher (1.3- to 1.7-fold) than those for corn oil chylomicrons at every time point examined after the start of lipid infusion. No other compositional differences in chylomicrons due to triglyceride source were observed. These results support the hypothesis that differences in efficiency of absorption and transport between saturated and unsaturated fat are sufficient to explain size differences in secreted chylomicrons in response to corn and butter oil infusions, and suggest that chylomicron number may be influenced by dietary fat saturation.

The effect of terminal ileal triglyceride infusion on gastroduodenal motility and the intragastric distribution of a solid meal

The infusion of triglyceride emulsions into the terminal ileum in concentrations that approximate those found in malabsorption results in the slowing of gastric emptying. The aim of this study was to characterize the changes in gastroduodenal motility responsible for this effect. Antropyloroduodenal pressures in 8 healthy volunteers were recorded with a manometric assembly incorporating a sleeve sensor across the pylorus and side holes in the antrum and duodenum. Each subject ingested a 100-g, 99m Tc-labeled solid meal; when approximately 25% of the meal had emptied from the stomach, a triglyceride emulsion (20% Intralipid) was infused into the terminal ileum at 1 ml/min for 45 min. Gastric emptying slowed markedly 15–30 min after the start of the lipid infusion (p = 0.01), and there was retrograde movement of the solid meal from the distal to the proximal portion of the stomach. During lipid infusion, there was a decrease in antral (p = 0.01), duodenal (p < 0.05), and propagated antropyloroduodenal pressure waves (p < 0.05) and an increase in isolated pyloric pressure waves (p < 0.05). The rate of gastric emptying correlated with antral pressure waves (r = 0.92, p < 0.001), duodenal pressure waves (r = 0.80, p < 0.01), and propagated pressure waves (r = 0.88, p = 0.0025) and correlated inversely with the number of isolated pyloric pressure waves (r = − 0.60, p = 0.05). The changes in antral, pyloric, and duodenal motility and the intragastric redistribution of a solid meal associated with ileal lipid infusion are likely to contribute to the delay in gastric emptying caused by this stimulus.

Release of Histamine-Like Substance from Mast Cells Following Intraperitoneal Administration of Fat Emulsion in Rats.

SummaryTwo triglyceride emulsions prepared for intravenous use in man have been examined for ability to release histamine from tissue mast cells in rat peritoneal cavity. The emulsions themselves had no direct action upon smooth muscle. Intraperitoneal injection of these materials caused rupture of the mast cells. The fluid recovered from the peritoneal cavity produced bronchiolar constriction in the pithed guinea pig and contraction of guinea pig ileum in vitro, indicating a significant histamine content. It is suggested that histamine release may play an important role in development of the occasional “anaphyloctoid” response following intravenous infusion of triglyceride emulsions in patients.