Introduction: One potential new therapy for epilepsy involves the omega-3 polyunsaturated fatty acids (PUFAs), and more specifically docosahexaenoic acid (DHA).   Methods: The anticonvulsant properties of the n-3 PUFAs were assessed in a series of different experiments. Subjects received chronic dietary supplementation, sub-chronic and acute injections of either fish oil (chronic) or DHA (sub-chronic, acute). Animals were tested in the electrical afterdischarge thresholds (ADTs) model in the amygdale and the maximal pentylenetetrazol (PTZ) model.   Results: Chronic, sub-chronic, and acute administrations of n-3 PUFAs were anticonvulsant in both the electrical stimulation and maximal PTZ models. In chronic experiments, amygala ADTs increased following 3 months of fish oil administration. Fourteen days of DHA i.p. injections increased latencies to maximal PTZ seizures. Acute injection of DHA s.c. and i.v. increased unesterified serum DHA and seizure latency. Conclusions: The present research suggests that n-3 PUFAs, and more specifically DHA, have anticonvulsant effects in vivo.

No description available.

Crude glycerol is the major byproduct of the biodiesel industry. In general, for every 100 pounds of biodiesel produced, approximately 10 pounds of crude glycerol are created. Because this glycerol is expensive to purify for use in food, pharmaceutical, or cosmetics industries, biodiesel producers must seek alternative methods for its disposal. Using crude glycerol as a carbon source for fermentation is a promising alternative use for this waste material. In this project, we propose to use crude glycerol in the fermentation of the microalga Schizochytrium limacinum, which is a prolific producer of docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with proven beneficial effects on treating human diseases such as cardiovascular diseases, cancers, and Alzheimer's. The first part of this study provided "proof-of-concept" that Schizochytrium limacinum was capable of utilizing crude glycerol while producing DHA. The results show that pretreated crude glycerol was a viable carbon source for algal growth and DHA production, with 75 g/L to 100 g/L of glycerol being the optimum concentration range. In addition to glycerol concentration, temperature, trace metal levels, ammonium acetate concentration, and NH4Cl concentration also had significant effects (P < 0.1) on algal DHA production. Optimizing these factors using response surface methodology led to a DHA yield of 4.91 g/L and a DHA productivity of 0.82 g/L-day. The second part of this study investigated the effects of impurities within the glycerol on DHA production and algal biomass composition, with a goal of ensuring that the algal biomass produced from crude glycerol can be safely utilized as an ingredient in omega-3 fortified foods or animal feed additives. Crude glycerol samples obtained from different biodiesel producers were tested. All the samples contained methanol, soaps, and various elements including calcium, phosphorus, potassium, silicon, sodium, and zinc. Both methanol and soaps in the glycerol negatively influence algal DHA production. The two impurities can be removed from the culture medium by evaporation through autoclaving (for methanol) or by precipitation through pH adjustment (for soap). The results showed that the crude glycerol-derived algal biomass contained 45-50% lipid, 14-20% protein, and 25% carbohydrate, with 8-13% ash content. Palmitic acid (C16:0) and DHA (C22:6) were the two major fatty acids in the algal lipid. ICP analysis showed that that boron, calcium, copper, iron, magnesium, phosphorus, potassium, silicon, sodium, and sulfur were present in the algal biomass, but no heavy metals (such as mercury) were detected. The crude glycerol-derived algal biomass had a high level of DHA and a nutritional profile similar to glucose-derived commercial algal biomass, suggesting a great potential for using crude-glycerol derived algae in omega-3 fortified food or feed. Overall, this study shows that crude glycerol can be used as a safe and effective substrate for algal culture to produce high levels of omega-3 fatty acids. With the rapid expansion of the biodiesel industry, there is an urgent need to develop new markets for large quantities of crude glycerol. This research provides an exciting opportunity to utilize a large quantity of this low grade glycerol. / Master of Science

This study investigated whether lutein and DHA enriched egg consumption can improve electrophysiological retina function for the prevention of age-related macular degeneration in Caucasian older adults. Thirty (male: n=11, female: n=19) healthy Caucasian older adults (64.0 ± 3.4 years) consumed two lutein and DHA enriched eggs (0.87 mg lutein/day, 220 mg DHA/day) daily for six weeks. Retina function, plasma and red blood cell (RBC) DHA, plasma lutein, lipid profiles, and lipoprotein subfractions were assessed at day 0 and 6 wks. The maximum amplitude of scotopic a-wave and photopic b-wave significantly increased along with plasma DHA concentrations No significant alterations in plasma Chol, HDL-Chol, LDL-Chol, triacylglycerides, plasma lutein and RBC DHA were present. A significant increase in large HDL particles and a decrease in intermediate sized HDL particles occurred. This study suggests that consuming two lutein and DHA enriched eggs daily may improve electrophysiological retina function without adversely altering plasma lipids in Caucasian older adults. / May 2017

Correct localization of lipidated cytosolic proteins to the plasma membrane (PM) is mediated by interactions between lipid anchors of proteins and cell membranes. Previously, dietary fish oil and its major n-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), have been shown to decrease Ras membrane association, concomitantly reducing rat colon tumor incidence and Ras signaling, compared with corn oil and linoleic acid (LA), a highly prevalent vegetable fat and dietary PUFA in the U.S. diet. In order to explore the potential regulatory role of the cellular lipid environment in PM targeting of lipidated proteins, young adult mouse colon (YAMC) cells were treated with 50 µM DHA, LA, or oleic acid (OA) 24 h prior to and 36-48 h after transfection with green fluorescent protein (GFP) fusion constructs of various lipidated cytosolic proteins. Relative expression of each GFP fusion protein at the PM and the Golgi in living cells was quantified using z-serial confocal microscopy and digital image processing. DHA differentially altered the subcellular localization of Ras isoforms and Src-related tyrosine kinases in a reversible manner. DHA significantly decreased the PM localization and increased the endomembrane association of H-Ras, N-Ras, and Lck, which are targeted to the PM via the exocytic pathway, regardless of their functional state. In contrast, the subcellular distribution of K-Ras and Fyn, of which transport is independent of the vesicular transport pathway, was unaffected by DHA. Moreover, DHA selectively inhibited lipidated cytosolic protein targeting since the PM delivery of transmembrane protein cargo was unaffected, indicating that DHA does not alter the bulk flow of secretory vesicular traffic. Overall, the present study presents compelling evidence that select dietary constituents with membrane lipid-modifying properties can differentially modulate subcellular localization of important lipidated signaling proteins depending on their intracellular trafficking route to the PM.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 105-117).

Triple negative breast cancers (TNBCs) account for ~15-20% of human breast cancers in Western countries. TNBCs are associated with poor prognosis and a low five year survival rate due, in part, to high rates of tumor recurrence, multi-drug resistance, metastasis, and therapeutic toxicity. Tumor initiating cells (TICs) or cancer stem cells (CSCs) are proposed to be responsible for the origin and maintenance of tumors as well as cancer recurrence, metastasis and drug resistance. Nutritionally-based low- to non-toxic therapeutic nutrients that eliminate both bulk tumor cells (non-TICs) and TICs have potential for prevention and treatment of primary and metastatic cancers, including TNBCs. Omega-3 fatty acid-docosahexaenoic acid (DHA) and certain vitamin E compounds [gamma- and delta- tocopherols [mathematical symbols] and tocotrienols [mathematical symbols]], separately and in combination, were investigated for their ability to eliminate non-TICs and TICs in human TNBCs and the mechanisms of action were studied. DHA induced apoptosis in several human TNBC cell lines via activation of endoplasmic-reticulum stress (ER stress) mediated C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP)/death receptor-5 (DR5) pro-apoptotic signaling involving caspases-8 and 9. DHA eliminated TICs as measured by elimination of aldehyde dehydrogenase active (ALDH⁺) population and inhibition of mammosphere formation. DHA eliminated TICs via suppression of phosphorylated Signal transducers and activators of transcription 3 (pStat-3) as well as downstream mediators cellular myelocytomatosis oncogene (c-Myc) and cyclin D1. SiRNA to Stat-3 reduced the number of ALDH⁺ TNBCs cells and reduced pStat-3, c-Myc, and cyclin D1 mediators, showing that Stat-3 is necessary for maintaining ALDH⁺ population and that c-Myc and cyclin D1 are downstream mediators of Stat-3. Studies also demonstrated that vitamin E compounds possess distinct anticancer activities. In summary, studies provide novel insights into therapeutic potential of DHA and certain vitamin E compounds for treatment of TNBCs. / text

published_or_final_version / Botany / Master / Master of Philosophy

The aim of this research was to isolate and characterize novel strains of marine protists with potential to commercially produce PUFAs. Twelve trips were made visiting 10 different locations in the Canadian Maritime Provinces. Sixty-nine strains were isolated and screened for biomass and fatty acid production. Those meeting specific criteria were selected for further investigation including characterization by 18S rDNA sequencing. Isolate ONC-KTB-56 produced the greatest amount of biomass (1 807 mg L-1) and fatty acids (24.6% dry weight). Of the total fatty acids, ARA, EPA and DHA comprised 0.89, 1.22 and 4.7 percent, respectively. Isolate ONC-KTB-14 produced 1 704 mg L-1 dry biomass with 5.4 percent fatty acids including 1.44, 1.35 and 37.5 percent, ARA, EPA and DHA, respectively. Through optimization of culture conditions biomass, fatty acid content and the proportions of specific fatty acids can be increased. With such optimization, there is potential for isolates ONC-KTB-14 and ONC-KTB-56 to be grown at a commercial scale for production of PUFAs.

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains xi, 87 p. : ill. Vita. Includes abstract. Includes bibliographical references.