Iodinated lipids

Ackman, R.G. and Eaton, C.A. (1976). Variations in fillet lipid content and some percent lipid-iodine value relationships for large winter Atlantic herring from southeastern Newfoundland. Journal of the Fisheries Research Board of Canada 33, 1634-1638. 

Chromatographic Migration of Lipids Iodinated in a Lactoperoxidase-Catalyzed Reaction... 

Starch hydrolysates Starch industry Starch-iodine Starch-lipid complex... 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Rhodamine 6G long-chain hydrocarbons [169] squalene, a-amyrin [170] methyl esters of fatty acids [171] glycerides [91] sterols [172, 173] isoprenoids, quinones [HI] lipoproteins [174] glycosphingolipids [175] phenolic lipids [176] phosphonolipids [177] increasing the sensitivity after exposure to iodine vapor [178,179]... 

In practice a few iodine crystals are usually placed on the bottom of a dry, closed trough chamber. After the chamber has become saturated with violet iodine vapor the solvent-free plates are placed in the chamber for 30 s to a few minutes. The iodine vapor condenses on the TLC layers and is enriched in the chromatogram zones. Iodine vapor is a universal detector, there are examples of its application for all types of substances, e.g. amino acids, indoles, alkaloids, steroids, psychoactive substances, lipids (a tabular compilation would be too voluminous to include in this section). 

Iodine is such a universal reagent. It was introduced by Mangold [i] as early as 1961 for the analysis of lipids and used again within a year by Bakrett [2] as a nondestructive reagent . 

Some substances, e. g. penicillin and pyrazolinone derivatives, are poorly detected by iodine staining with detection limits of 2-4 pg substance per chromatogram zone [6, 7]. The limits for lipids and for opium alkaloids lie with 50-500 ng [8] in the middle nanogram range [9]. 

An excellent example of PLC applications in the indirect coupling version is provided by the works of Miwa et al. [12]. These researchers separated eight phospholipid standards and platelet phospholipids from the other lipids on a silica gel plate. The mobile phase was composed of methylacetate-propanol-chloro-form-methanol-0.2% (w/v) potassium chloride (25 30 20 10 10, v/v). After detection with iodine vapor (Figure 9.2), each phospholipid class was scraped off and extracted with 5 ml of methanol. The solvent was removed under a stream of nitrogen, and the fatty acids of each phospholipid class were analyzed (as their hydrazides) by HPLC. The aim of this study was to establish a standardized... 

The iodine number is an indication of the degree of unsaturation of triglycerides, and is the amount of iodine (in mg) required to react with 1 g of lipid material. 

Oxidative stress Lipid oxidation Oxygen absorption Manometric, polarographic Diene conjugation HPLC, spectrophotometry (234 nm) Lipid hydroperoxides HPLC, GC-MS, chemiluminescence, spectrophotometry Iodine liberation Titration Thiocyanate Spectrophotometry (500 nm) Hydrocarbons GC Cytotoxic aldehydes LPO-586, HPLC, GC, GC-MS Hexanal and related end products Sensory, physicochemical, Cu(II) induction method, GC TBARS Spectrophotometry (532-535 nm), HPLC Rancimat Conductivity F2-iP GC/MS, HPLC/MS, immunoassays... 

Iodine liberation is one of the oldest and most commonly used methods for assessing lipid substrate oxidation. In this method, hydroperoxides and peroxides oxidize aqueous iodide to iodine, which is then titrated with standard thiosulfate solution and starch as endpoint indicator. The peroxide value is calculated as milliequivalents of peroxide oxygen per kilogram of sample. 

Iodine-131-labeled Lipiodol, a polyiodinated poppy seed oil which becomes particulate on dispersion in aqueous media, has been used for some time in treatment of hepatocellular carcinoma by arterial injection. This targeting approach has been coupled with the superior radioactivity properties of rhenium radioisotopes by exploiting the lipid solubility of... 

Iodine vapour Place the dried plate in a sealed tank containing a few iodine crystals Dark yellow-brown spots appear within a few minutes where lipids have absorbed the iodine. Unsaturated lipids are more intensely stained. Glycolipids do not stain significantly... 

Another colorimetric method of the associated PEG-lipid might be performed using the method described by Baleux (51). This assay consists of the formation of a complex between the PEG moiety and iodine forming a solution absorbing at 500 nm. This method is less sensitive than the previous one because it does not rely on a specific chemical function on the PEG, although it allows for wider type of PEG-lipid to be quantified. 

Fig. C.2 Thin Layer Chromatography. An example of a lipid containing sample developed and stained with Iodine vapors.

Emulsions based on lipophilic iodized and/or bromated substances with emulsifiers and derivatives of cyclopenta-phenanthrene Polyiodinated phenyl fatty acid compoimds Emulsion of iodinated lipids 6-Iodoethylated starch... 

The first extensively tested RES-specific contrast agent on the basis of iodinated lipids was EOE-13 with its precursors, AG 52-315 and AG 60-99. EOE-13 is an aqueous emulsion of the iodinated ester of poppy seed oil and is able to selectively enhance the normal liver and spleen parenchyma [10-12]. However, severe adverse events such as headache, fever and chills prevented further use of these contrast agents [13-15], although their extent could be decreased by hydrocortisone given prior to contrast injection. 

Practically all available iodinated extracellular X-ray contrast agents have been encapsulated into liposomes using different lipids and methods of preparation. Table 1 gives a short and intentionally incomplete overview of some of the approaches. The first liposomal contrast agent preparation that was tested in humans contained diatrizoate [48]. The injected dose was up to 0.5 ml kg k The preparation was effective even in plain radiography where lesions down to 0.8-1.0 cm could be detected in patients. However, adverse events such as fever and hyperthermia, which occurred in 30% of the patients, limited further use. We have incorporated iopromide into MLVs that were prepared from phosphatidyl choline (PC), cholesterol and stearic acid at a molar ratio of 4 5 1 using the ethanol-evaporation technique [44]. The liposomes can be stored freeze-dried and they are reconstituted before use by... 

A series of iomeprol-containing liposomes were evaluated in animals by Petersein et al. [62] and in healthy volunteers by Spinazzi et al. [63,64]. BR2 and BR21 are liposomes made of phosphatidyl choline (PC),dipalmitoyl phospatidic acid (DPPA) and cholesterol at a molar ratio of 2 1 (PC -i- DPPA/cholesterol) with an iodine content of 260 mg mL (BR2) and 320 mg mL" (BR21), respectively, and a size of 0.4 pm. BR2 contains 40 mg lipid mL and BR21 20 mg mL L In rabbits, BR2 tended to provide a higher and more persistent CT enhancement than BR21. 

In this section the first two approaches, modification of biliary contrast agents and iodination of nutritional lipids will be described. 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

So far, none of these iodinated lipids has reached phase I clinical trials. 

Ivancev I, Lunderquist A, McCuskey R, McCuskey P, Wretlind A (1989) Experimental investigation of a new iodinated lipid emulsion for computed tomography of the liver. Acta Radiol 30 407... 

Sundin A, Ahlstrom H, Graf W, Magnusson A (1994) Computed tomography of experimental liver metastases using an iodinated hepatocyte-specific lipid emulsion a correlative study in the nude rat. Invest Radiol 29 963... 

Bergman A, Sundin A, Magnusson A (1997) An iodinated lipid emulsion for CT of the liver. Comparison with iohexol in the detection of experimental hepatic metastases. Acta Radiol 38 55... 

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