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Fecapentaene-12 and fecapentaene-14 are genotoxic polyunsaturated ether-lipids produced by the colonic microflora in humans and pigs. Although the fecapentaenes have been extensively characterized, little is known about the nature of the precursors from which they are produced. We purified one form of these precursors from feces of an individual who excreted high levels of fecapentaene-12 and its precursors. Purification was carried out by a series of extractions and precipitation in organic solvents followed by silica and amine high performance liquid chromatography. The purified precursor had identical UV spectral characteristics as the fecapentaenes indicating that it contained the same ether-linked pentaenyl functional group. However, it was not mutagenic. The precursor was amphiphilic in nature, behaving like a synthetic 'model' ether-phospholipid on silica and C thin layer chromatography. When incorporated into phosphatidylcholine micelles it could be hydrolyzed in vitro by a combination of lipase and phospholipase C to fecapentaene-12. Our findings indicate that the general structure of this precursor is that of a phospholipid, specifically a plasmalogen-the exact structures of which remain to be determined. [ABSTRACT FROM AUTHOR]

The standard of care to treat hypothyroidism is daily administration of levo-thyroxine (LT4). This is based on the understanding that deiodinases can restore production of T3 and compensate for the small amounts of T3 that are normally produced by the thyroid gland. However, pre-clinical and clinical evidence indicating that deiodinases fall short of restoring T3 production is accumulating, opening the possibility that liothyronine (LT3) might have a role in the treatment of some hypothyroid patients. LT3 tablets taken orally result in a substantial peak of circulating T3 that is dissipated during the next several hours, which is markedly distinct from the relative stability of T3 levels in normal individuals. Thus, the effort to developing new delivery strategies for LT3, including slow release tablets, liquid formulations, use of T3-related/hybrid molecules such as T3 sulfate, poly-zinc-T3 and glucagon-T3, nanoparticles containing T3, subcutaneous implant of T3-containing matrices, and stem cells for de novo development of the thyroid gland. This article reviews these strategies, their applicability in animal models and translatability to humans.

We report our comparative studies of myo- and chiro-[3H]inositol distribution in control nondiabetic Wistar and spontaneous nonobese insulin-resistant Type II diabetic G.K. rat tissues following 78-h labeling period. From various tissue extracts, free inositols, inositol phosphates, and inositol phospholipids were isolated and analyzed. Our findings demonstrate (1) a significant difference in the metabolism of myo- and chiro-inositol in normal Wistar and G.K. rats, (2) a severe defect in conversion of myo-[3H]inositol to chiro-[3H]inositol at the inositol phospholipid level of insulin-sensitive tissues of the G.K. rat, (3) an increased incorporation of myo-[3H]inositol into purified inositol phospholipids of the G.K. rat consistent with a decreased conversion to chiro-[3H]inositol, (4) the presumed presence of a pathway which incorporates chiro-[3H]inositol into inositol phospholipids, and which is overactive in the G.K. rat compared to the Wistar rat, and (5) no or minimal conversion of chiro-[3H]inositol to myo-[3H]inositol.