published_or_final_version / Surgery / Master / Master of Medical Sciences

The present research examined the hypothesis that omega-3 polyunsaturated fatty acids would increase seizure threshold in rats in vivo, and reduce neuronal excitability in mouse hippocampal slices. Seizure thresholds were measured in rats using the maximal pentylenetetrazol and electrical stimulation seizure tests following α-linolenic acid (ALA) or docosahexaenoic acid administration. ALA raised seizure threshold in the maximal PTZ seizure test, but this effect probably occurred because ALA displaced DHA from liver to the brain. DHA itself was therefore tested in the PTZ and electrical stimulation seizure tests. Direct administration of DHA by subcutaneous injection raised seizure thresholds in the PTZ seizure test, which models tonic-clonic attacks in humans. Dietary enrichment with DHA raised afterdischarge seizure thresholds in the cortex and amygdala, which model simplex and complex partial seizures in humans, although this effect took some time to occur. In vitro, the application of DHA also reduced the incidence of excitatory sharp waves in mouse hippocampal slices. This effect did not appear to be due to either an increase in GABAergic inhibitory tone, nor to a decrease in glutamatergic drive. The fatty acid composition of phospholipids and unesterified fatty acids were measured in the brain following microwave fixation in order to determine whether the effects of DHA on seizure thresholds were due to its de-esterification from the phospholipid membrane. The assay surprisingly revealed that subcutaneous administration of DHA at a dose that raised seizure threshold, increased unesterified arachidonic acid, but not unesterified DHA concentrations during seizures. The results of these studies support the hypothesis that DHA raises seizure threshold in rats, and reduces neuronal excitability in vitro. The effects of DHA on seizure threshold are possibly mediated by the de-esterification of arachidonic acid, which is known to have effects on the voltage-dependent sodium channel.

There is a wealth of scientific evidence associating the dietary intake of omega 3 long-chain polyunsaturated fatty acids with beneficial health properties. In this study, alternative natural sources of these polyunsaturated fatty acids are sought from novel low temperature isolated fungi. Over 100 low temperature isolated fungi were screened for very long chain polyunsaturated fatty acids (VLCPUF As), such as C20:5 n3 and C22:6 n3. Of those screened, only ten fungi were capable of VLCPUFA production, with Mortierella the predominant VLCPUF A producing species. Four Oomycete species were also capable of VLCPUF A production. It is thought that only basal fungal lineages, such as species from the Chytridiomycota and Zygomycota, are capable of VLCPUF A production. It was also found that VLCPUF As are not essential for growth at low temperatures, as Penicillium rugulosum, capable of producing 'fatty acids no longer or more unsaturated than C18:3 n3, demonstrated over 2 g of biomass per 100 ml of broth when grown at 5°C. This indicates that trienoic fatty acids are sufficient for maintaining membrane fluidity, although other factors may play a role in P. rugulosum's low temperature growth. Comparatively, VLCPUFA producing Mortierella species produced 200-250 mg of biomass, whereas the majority of non- VLCPUF A producing isolates produced 106-115 mg of biomass per 100 ml of broth. The total lipid unsaturation indices of nine isolates grown under three temperature regimes showed that the lowest growth temperature, 5°C, produced the highest un saturation index value III SIX of the organisms. 15°C produced the highest unsaturation index value in two of the isolates. This suggests that temperature has an effect on fungal lipid composition, and that lower temperatures may increase lipid unsaturation levels. It was also found that the ~6 elongase, initially identified from Mortierella alpina, is indicative for VLCPUF A producing fungi. The genomic conserved sequence found within ~6 elongases was used to develop primer sets that could be used with a PCR based methodology to screen fungal isolates for VLCPUF A production. The method successfully identified VLCPUF A producing Mortierella and Allomyces species, and was not found to amplify non-Ad elongases. Finally, recombinantPhaffia rhodozyma strains were developed using the ~5 desaturase and ~6 elongase from Mortierella alpina. The fatty acid profiles of the recombinant strains displayed novel fatty acids such as C20:2 n6 and C20:3 n3, and putatively, C18:2 ~5, 9 and C18:3 ~5, 9, 12 which correlated with the inserted genes.

Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women's Health Initiative prospective cohort (n = 134,017). During a mean 11.7 years (1993-2010), 1952 incident CRC cases were identified. Cox regression models computed multivariate adjusted hazard ratios to estimate the association between dietary factors and CRC risk. Assessing fiber and fat individually, there was a modest trend for lower CRC risk with increasing intakes of total and insoluble fiber (p-trend 0.09 and 0.08). An interaction (p = 0.01) was observed between soluble fiber and DHA + EPA, with protective effects of DHA + EPA with lower intakes of soluble fiber and an attenuation at higher intakes, however this association was no longer significant after correction for multiple testing. These results suggest a modest protective effect of higher fiber intake on CRC risk, but not in combination with dietary fat subtypes. Given the robust results in preclinical models and mixed results in observational studies, controlled dietary interventions with standardized intakes are needed to better understand the interaction of specific fat and fiber subtypes on colon biology and ultimately CRC susceptibility in humans.

Background: The role of aspirin (100 mg daily) and omega-3 fatty acids (FA) (1 g daily) for primary prevention of cardiovascular disease in diabetes is being investigated in the 2x2 factorial design ASCEND trial. To support the interpretation of the trial's efficacy findings, it is important to compare self-reported compliance by participants with measures of the biochemical effects of each intervention. The previous data on the effect of supplementation with omega-3 FA on coronary heart disease is uncertain. Methods: The ASCEND trial randomly allocated 15480 people with diabetes (94% type 2 DM) who do not already have diagnosed occlusive arterial disease to receive aspirin or placebo and to omega-3 FA or placebo. Blood and urine samples were collected by mail at baseline and after 3 years follow-up. The effectiveness of aspirin to suppress urinary thromboxane B2 (UTxB2), a marker of platelet activity, and, of omega-3 FA supplements to increase red cell membrane omega-3 index were assessed. A systematic review of previous trials of omega-3 FA was conducted to summarize the prior evidence for the effects of omega-3 FA supplements on major vascular events (MVEs). Results: Aspirin reduced UTxB2 levels by 67% (63-70%) (p < 0.0001) compared with placebo, from 3453 pg/mg (95% CI 3061-3895) at baseline to 1190 pg/mg (1100-1287) on those allocated to aspirin during the trial. During follow-up, the omega-3 index increased by 33% (95% CI 26%-39%) in those allocated omega-3 FA compared to placebo (p < 0.0001). The meta-analysis of previous studies of omega-3 FA showed no effect on MVEs (HR 0.97; [0.93-1.01]) overall or in any pre-specified sub-groups. Conclusions: Low dose aspirin and omega-3 FA are biochemically effective at reducing UTxB2 and increasing the omega-3 index, respectively. Previous trials show that supplementation with omega-3 FA had no significant effect on MVEs. The results of the ASCEND trial, assessing the effects of both aspirin and omega-3 FA on MVEs, will be available in 2018.

No description available.

Metabolic syndrome is a grouping of criteria that includes hypertension, glucose intolerance, truncal obesity and/or a high body mass index (BMI), insulin resistance, high very-low-density lipoproteins, high triglycerides, and low high-density lipoproteins. Metabolic syndrome is a problem in Hispanic children due to increasing obesity rates and a predisposition for insulin resistance in the Hispanic population. Omega-3 fatty acid supplementation has been shown to decrease triglycerides, body mass, insulin resistance, and hypertension while increasing HDL. Inflammatory markers are also reduced after omega-3 supplementation. More research is needed on the supplementation of omega-3 fatty acids in children before guidelines are written. Supplementation and overall intake levels of EPA and DHA can be determined through food frequency questionnaires. Research at this time indicates that supplementation with omega-3 fatty acids could be beneficial for Hispanic children who already partially met the criteria for metabolic syndrome, and is probably not harmful.

Ob eine Immunonutrition einen Nutzen in der Versorgung schwer kranker oder chirurgischer Patienten bringt, ist Thema kontroverser Diskussionen. Dabei scheint unklar, welches Patientenklientel von welcher Zusammensetzung verschiedener immunmodulatorischer Substanzen am meisten profitiert. Zudem ist nicht einheitlich geklärt, zu welchen Zeitpunkten und über welche Zeiträume die Immunmodulation den größten Nutzen bringt. Die hier durchgeführte Studie wurde konzipiert, um zu untersuchen, ob die Patienten, die einer aortokoronaren Bypassoperation unter Einsatz der Herz-Lungen-Maschine zugeführt werden, eine Verbesserung ihres klinischen Outcomes zeigen, wenn sie immunmodulatorische Substanzen perioperativ erhalten. Die konkreten Fragestellungen für diese Arbeit lauten daher: 1) Kann die Immunonutrition mit Glutamin, ௰-3-Fettsäuren und antioxidativ wirksamen Vitaminen die Inzidenz von postoperativen Infektionen bei Patienten, die einer aortokoronaren Bypassoperation zugeführt werden, verringern? 2) Verkürzt sich die Liegedauer der Patienten auf der Intensivstation und nach Verlegung auf Normalstation postoperativ bei regelmäßiger Einnahme der immunmodulierenden Substanzen über den Zeitraum des stationären Aufenthaltes? 3) Verbessert sich das klinische Outcome der Patienten durch die perioperative Substitution insgesamt, durch ein selteneres Auftreten von häufigen Komplikationen und Kreislaufinstabilitäten? Zu diesem Zweck wurde eine Kohortenstudie mit 137 Patienten durchgeführt, wovon sich 97 Patienten in der Kontrollgruppe und 40 in der Experimentalgruppe befanden. Die Patienten der Experimentalgruppe erhielten ab dem Tag ihrer stationären Aufnahme 2 unterschiedliche Substanzen zur oralen Einnahme verabreicht. Die eine enthielt einen hohen Anteil an Glutamin und antioxidativ wirksamen Substanzen (Glutamine Plus®) und die andere einen hohen Gehalt an ௰-3-Fettsäuren (Supportan® Drink). Das Glutamine Plus® wurde morgens und abends, der Supportan® Drink mittags verabreicht. Die Substitution erfolgte über den kompletten stationären Aufenthalt, abgesehen von dem Tag der Operation selber. Die Blutentnahmen für die entsprechenden infektiologischen Parameter erfolgten zu den Zeitpunkten präoperativ, 6 Stunden nach Ende der Operation, 2 Tage postoperativ und vor der Entlassung. Es zeigte sich, dass die Patienten, die die Substanzen erhielten, weniger postoperative Infektionen entwickelt hatten, als die Patienten in der Kontrollgruppe. Das wurde aus einer signifikanten PCT-Erhöhung in der Kontrollgruppe abgeleitet. Allerdings hatte diese postoperative Komplikation keine Auswirkung auf die Liegezeit der Patienten auf der Intensivstation oder auf die Dauer des stationären Aufenthaltes nach Verlegung von der Intensivstation auf eine periphere Station zur Folge. Ebenfalls zeigten sich keine Unterschiede zwischen den beiden Kohorten in der Notwendigkeit einer antibiotischen Therapie, sowie im Auftreten von Kreislaufinstabilitäten oder den häufigsten Komplikationen. / The influence of an immunonutrition with glutamine, omega-3-fatty acids and antioxidative vitamins on the postoperative progress of cardiosurgical patients

Omega-3 fatty acids are increasingly recognised as playing an important role in human brain development and mental health. The polyunsaturated fatty acids (PUFAs) include omega-3 and omega-6 fats which are essential fatty acids (EFAs), consumed via the diet. Omega-3 fatty acids are particularly abundant in fish oils. The omega-3 fatty acids are being focused on for their role in depression, the main types being docosahexaenoic acid (DHA), which is abundant in neural tissue, and also eicosapentaenoic acid (EPA) which is biologically very active. There is an emerging literature in relation to omega-3 fatty acid blood levels in depression and the effects of treatment with omega-3. Strong epidemiological evidence has also been published indicating an association between a population's fish intake and depression rates. A specific research focus on omega-3 as a treatment for depression in the perinatal period is also starting to emerge. The importance of this particular area is enhanced by the knowledge that omega-3 depletion occurs during the perinatal period due to fetal diversion for neurodevelopment. In view of the lay public promotion of omega-3 and its appeal to women as a 'natural therapy', there is a need to scientifically evaluate its effectiveness to treat depression in the perinatal period. It is also important to investigate omega-3 as an alternative to antidepressants given the ongoing uncertainties regarding their safety in pregnancy. In this thesis a literature review presents current research relating to this field. This is followed by a description of the methodology and results for the two trials conducted. The results of the double-blind randomised placebo controlled trial of omega-3 as a treatment for depression in the perinatal period were essentially negative. However this result is limited by the small sample size in the study and therefore it may be unwise to interpret the result as conclusive. The case-control study confirmed the hypothesis that omega-3 levels were more depleted in depressed women compared to non-depressed women. A discussion of the results and trial limitations then follows in the thesis. It is concluded that further larger studies are warranted in this area.

A series of experiments were conducted to explore factors affecting transfer of value-added ingredients from the diet to table eggs, with the goal of contributing to improvements in the enrichment process. Flaxseed-based ω-3 PUFA enrichment did not reduce lutein enrichment. The combine enrichment of lutein and ω-3 PUFA had decresed lipid oxidation potential. Also, when fed a ω-3 PUFA diet, birds scored as energetic Efficient had longer and wider villi, resulting in greater absorptive surface area/villi than Non-efficient hens. However, histomorphological differences did not affect transfer of ω-3 PUFA from diet to egg. Finally, birds fed graded levels of ω-3 PUFA to characterize change in lipid profile of egg and blood plasma in time reached a plateau in total ω-3 PUFA/egg in 5.9 to 6.6d, with High birds reaching the target of 300 mg/egg in 5d. Egg enrichment can be modulated by changes to the hen diet. / Animal Science