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As much as 10% of the US population will experience at least one bout of depression within their lifetime. It has been reported that an increased time spent with major depressive disorder (MDD) results in a decreased volume in the hippocampus. This decreased volume is the result of apoptosis, or programmed cell death. In recent years it has become known that new neurons (neurogenesis) are continuously born in the hippocampus of humans. In fact, it now appears that antidepressant drug efficacy may be dependent on adult neurogenesis in the hippocampus. At least six epidemiological studies have shown an inverse correlation between seafood intake and prevalence of mood disorders (p [less than]0.05 or better). There is mounting evidence that this result is due to fish oils containing the long-chain, poly-unsaturated, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although extensive study has been undertaken using both of these omega-3s together, very little has been done to determine which fatty acid has the greater effect. Although previously thought to be readily interconvertible, there is mounting evidence that these two lipids are not treated equally in the body. EPA has produced greater cell proliferation over DHA in the B-lymphocyte cells, and DHA has even been known to cause a decrease at higher concentrations. Differences have also been reported in both molecular and behavioral outcomes. This research tested the hypothesis that EPA facilitates proliferation and survival of neuronal precursor cells to a greater extent than does DHA. Human neuronal precursor cells were grown in the presence of EPA, DHA, and varying ratios of EPA and DHA to determine their dose-response relationships. While there were no large effects on proliferation or differentiation, EPA, but not DHA, protected cells from iron-induced oxidative stress. This protection appears to be, at least in part, the result of altered p53 translocation in EPA-treated cells. Future work will be needed to determine the role of this molecular protection in the antidepressant activity of EPA. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Master of Science. / July 16, 2009. / Includes bibliographical references. / Cathy Levenson, Professor Directing Theis; Jodee Dorsey, Committee Member; Michael Meredith, Committee Member.

Dissertation (DScD) -- Boston University, Henry M. Goldman School of Dental Medicine, 2010 (Department of Periodontology and Oral Biology). / Diabetes and periodontal disease exhibit a bidirectional relationship centered on an enhanced inflammatory response manifested both locally and systemically. The observation that hyperglycemia by itself, in the absence of additional inflammatory signals, promotes a proinflammatory environment indicates that diabetes is an independent risk factor for periodontal disease. Leukocyte pre-activation or priming in diabetes has been demonstrated. Excessive ROS release by leukocytes, upregulation of pro-inflammatory mediators and adhesion molecules are characteristic to T2DM-associated low-grade inflammation. However, the mechanisms by which chronic hyperglycemia leads to leukocyte activation are not fully understood. [TRUNCATED]

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22827号 / 医博第4666号 / 新制||医||1047(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 髙橋 良輔, 教授 Shohab YOUSSEFIAN / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA, C20:5, n-3) and docosahexaenoic acid (DHA, C22:6, n-3), have many medically established benefits against cardiovascular diseases, cancers, schizophrenia, and Alzheimer's. Currently, fish oil is the main source of omega-3 fatty acids, but there are many problems associated with it such as undesirable taste and odor, and heavy metal contamination. As a result, it is necessary to seek alternative production sources based on various microorganisms. In this thesis we have developed a novel microfungal culture process to produce EPA from the crude glycerol byproduct generated in biodiesel industry. This process provides both an alternative source of omega-3 fatty acids and a benefit to the biodiesel industry. Indeed, as oil prices reach historical highs, biodiesel has attracted increasing interest throughout the United States. The disposal of the crude glycerol byproduct has been a challenge faced by the biodiesel producers. Crude glycerol presents a cheap carbon source for growth of many microorganisms. In this thesis, we tested the feasibility of using crude glycerol for producing eicosapentaenoic acid (EPA, 20:5, n-3) by one algal species, Phaeodactylum tricornutum and two fungal species, Mortierella alpina and Pythium irregulare. We observed that the algal growth is inhibited in the crude glycerol while the fungi can grow very well in crude glycerol-containing medium. The fungus M. alpina produced significant amount of ARA but negligible amount of EPA. P. irregulare produced significant amount of biomass as well as a relatively high level of EPA. The maximum dry biomass for the P. irregulare culture was 2.9 g/L with an EPA productivity of 7.99 mg/L-day. Based on these results, we concluded that P. irregulare was a promising candidate for EPA production from biodiesel derived crude glycerol. Further optimization work showed that P. irregulare grown 30 g/L crude glycerol and 10g/L yeast extract results in the highest level of EPA production. A temperature of 20o C is optimal for high fungal biomass and EPA levels. Addition of vegetable oil (at 1%) enhanced the EPA production and almost doubled the amount of biomass reached. Soap inhibits growth as well as EPA production severely even in small amounts. Methanol completely inhibits growth. The final optimized growth conditions for the fungus P.irregulare were a medium with 30g/L of crude glycerol, 10 g/L of yeast extract at a pH of 6 with 1% supplementation of oil, at a temperature of 20o C for a period of 7 days.Thus we have established that the fungus P.irregulare can be used successfully to produce high mounts of EPA from crude glycerol. / Master of Science

Yes / Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation. / Efficacy and Mechanism Evaluation Programme. Grant Number: NIHR128210. Cancer Research UK. Grant Number: C23434/A24939

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21161号 / 農博第2287号 / 新制||農||1060(附属図書館) / 学位論文||H30||N5135(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 栗原 達夫, 教授 小川 順, 教授 阪井 康能 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Thesis (MA)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Schizophrenia is known to produce positive (e.g. hallucinations) and negative symptoms (e.g. social withdrawal). Cognitive dysfunction has long been recognised as common in schizophrenia and is now accepted as a third cardinal feature, thought strongly to be associated with negative symptoms. While positive symptoms may respond well to antipsychotic medication, the negative symptoms have typically been resistant to all forms of intervention. A current study looking at the efficacy of Eicosapentaenoic Acid (EPA), indicated a potential for negative symptoms to improve, although not significantly (P=O.14). The purpose of this research was to expand the above mentioned study, by evaluating the potential of EPA for improving cognitive function in patients with schizophrenia. Forty patients diagnosed with schizophrenia were randomly ascribed to one of two groups in a 12 week, double-blind, placebo-controlled study. The following neuropsychological tests were administered to patients at baseline and end point: Mini Mental State Examination (MMSE); Rey Auditory-Verbal Learning Test (RAVLT); Visual Reproduction, Wechsler Memory Scale - Revised (VR, WMS-R); Rey-Osterreith Complex Figure Test (ROCFT); Trail Making Tests (TMT-A; TMTB); Controlled Oral Word Association Test (COWAT); Similarities, South African Wechsler Adult Intelligence Scale - Revised (Similarities, SAWAIS-R); Boston Naming Test (BNT). There were no overall significant differences in neuropsychological function between the experimental (EPA) and the control (Placebo) group. In some isolated tests the experimental group did significantly better than the control group, but for other tests the control group did significantly better than the experimental group. Large intragroup variation - particularly within the EPA group - was indicated. In the EPA group only one out of 25 independent neuropsychological test scores showed a significant correlation with the symptom severity on the Positive and Negative Syndrome Scale (PANSS) total score (% change). There were no significant correlations between any of the neuropsychological test scores in the EPA group and on the dyskinesia subscore of the Extrapyramidal Symptom Rating Scale (ESRS). There was no evidence to support the hypothesis that EPA improved cognitive functioning in patients with schizophrenia. / AFRIKAANSE OPSOMMING: Dit is bekend dat skisofrenie positiewe (bv. hallusinasies) en negatiewe simptome (bv. sosiale onttrekking) voortbring. Kognitiewe disfunksie word lank reeds beskou as algemeen in skisofrenie en word nou aanvaar as 'n derde kardinale eienskap wat sterk geassosieer word met negatiewe simptome. Terwyl positiewe simptome goed reageer op antipsigotiese medikasie, is die negatiewe simptome tipies meer weerstandig teen all vorme van intervensie. 'n Huidige studie wat die effektiwiteit van Eicosapentaenoic Acid (EPA) ondersoek, het 'n potensiaal vir die verbetering in negatiewe simptome aangedui, alhoewel nie beduidend nie (P=O.14). Die doel van hierdie navorsing was om bogenoemde studie uit te brei, deur te evalueer wat die potensiaal van EPA is om kognitiewe simptome in pasiente met skisofrenie te verbeter. Veertig pasiente gediagnoseer met skisofrenie is ewekansig toegewys aan een van twee groepe in 'n 12 weke, dubbel-blinde, plasebo-gekontroleerde studie. Die volgende neurosielkundige toetse is afgeneem op pasiente by basislyn en eindpunt: Mini Mental State Examination (MMSE); Rey Auditory-Verbal Learning Test (RAVLT); Visual Reproduction, Wechsler Memory Scale - Revised (VR, WMS-R); Rey-Osterreith Complex Figure Test (ROCFT); Trail Making Tests (TMT-A; TMT-B); Control/ed Oral Word Association Test (COWAT); Similarities, South African Wechsler Adult Intelligence Scale - Revised (Similarities, SAWAIS-R); Boston Naming Test (BNT). Daar was geen beduidende verskille in neurosielkundige funksionering tussen die eksperimentele (EPA) en kontrole (Plasebo) groep nie. In 'n paar geïsoleerde toetse het die eksperimentele groep beduidend beter as die kontrolegroep gevaar, maar op ander toetse het die kontrolegroep beduidend beter as die eksperimentele groep gevaar. Groot intragroep variansie - in veral die EPA groep is aangetref In die EPA groep het slegs een uit die 25 onafhanklike neurosielkundige toetstellings gedui op 'n beduidende korrelasie met die ems van simptome op die Positive and Negative Syndrome Scale (PANSS) totale telling (% verandering). Daar was geen beduidende korrelasie tussen enige van die neurosielkundige toetstellings in die EPA groep en op die diskinesie-subtelling op die Extrapyramidal Symptom Rating Scale (ESRS) nie. Daar was geen bewyse om die hipotese te steun dat EPA kognitiewe funksionering in pasiënte met skisofrenie verbeter nie.

by Lai Bo San Paul. / "April 1997." / "Revised May 1998." / Thesis (M.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 175-228). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstract in Chinese.

Crude glycerol is the major byproduct of the biodiesel industry. There is an abundance of this byproduct and purifying it for use in industries such as food, pharmaceutical, or cosmetic is prohibitively expensive. Developing an alternative use for crude glycerol is needed. Utilizing it as a carbon source in the fermentation of algae is one potential method for using this under-utilized byproduct. In this research, crude glycerol is used in the mixotrophic production of the alga, Phaeodactylum tricornutum, which is an eicosapentaenoic acid (EPA) producing diatom. Mixotrophic growth is when cells perform autotrophic and heterotrophic modes of growth concurrently. EPA is an omega-3 polyunsaturated fatty acid that has been demonstrated to have a multitude of beneficial health effects, including maintaining human cardiovascular health, treating cancer and human depression diseases, and an anti-obesity effect. In this study, the potential of using crude glycerol in batch mode mixotrophic culture of P. tricornutum was investigated. Once the mixotrophic culture was established, parameters involved in increasing the biomass and EPA production were optimized. These included nitrogen source, level of supplemental carbon dioxide, and concentration of crude glycerol. Using nitrate, 0.08 M crude glycerol, and 3% (vol/vol) carbon dioxide led to the highest biomass productivity of 0.446 g L?? day?? and the highest EPA productivity of 16.9 mg L?? day?? in batch mode culture. The continuous culture of the mixotrophic culture was then performed following the batch culture optimization. The effects of dilution rate were observed in continuous culture with the parameters of nitrate as the nitrogen source, 0.08 M crude glycerol, and 3% (vol/vol) carbon dioxide held constant. The highest biomass productivity of 0.612 g L?? day?? was obtained at D = 0.24 day??. The highest EPA productivity of 16.5 mg L?? day?? was achieved at both D = 0.15 day?? and D = 0.24 day??. The maximum specific growth rate was estimated from the washing out dilution rate and was determined to be around 0.677 day??. Overall, it was found that crude glycerol increases the biomass and EPA productivity of Phaeodactylum tricornutum. Continuous culture with the use of crude glycerol can further increase these measurements. The potential for scaling up studies is demonstrated by these results and can help lead to a market for this abundant, little-used byproduct of the biodiesel industry. / Master of Science