No description available.

Submerged cultures of Aspergillus flavus and Aspergillus niger were grown in a medium containing avidin, a substance which serves as an inhibitor of the conversion of acetate to malonate. Control cultures were grown without the addition of avidin.Analysis of the fatty acids produced by cultures grown in a medium containing avidin gave an increase in C16 fatty acids and a decrease in C18 fatty acids, suggesting that malonate plays an important role in the elongation of long chain fatty acids in these organisms. This effect was observed for five to fifteen hours.Evidence of the conversion of palmitate to stearate to oleate to linoleate was presented. That the conversion of oleate to linoleate involves a desaturase which is highly specific is suggested by the observation that, although there are a number of monoenoic acids present in these organisms, the only dienoic acid found was linoleic acid.

The work detailed in this thesis is mainly concerned with the carbonylation of fatty acid derivatives, using carbon monoxide atmospheres in the presence of a transition metal. The two systems under study were the conversion of oleonitrile to a cyano-ester using a cobalt catalyst, and formation of isocyanates from amines in the presence of a palladium salt. The objectives of each study were: (i) to assess the influence of physical conditions on the reaction (i.e. pressure, time and temperature);(ii) to examine the effect of various additives on the system (i.e. phosphines, iodides and bases); and (iii) to identify any catalytic species observed under reaction conditions.Three major techniques were employed in each study: autoclave reactions, high pressure infra-red studies and atmospheric pressure nitrogen-line chemistry. The proposed underlying reaction mechanism was examined critically for each system, comparisons being drawn between the postulated catalytic species and those actually observed by high pressure infra-red spectroscopy. The chemical properties of the proposed catalytic intermediates are discussed in relation to the effect of co-reactants on the system. In the case of the carbonylation of oleonitrile the high pressure infra-red studies are consistent with the proposed reaction mechanism based upon the acyl complex RCOCo(CO)(_4). Although the infra-red study on the carbonylation of amines did not reveal any definite information, the results of other experiments were found to be consistent with a system based upon a carboxamido species L(_2)Pd(Cl)(CONRR').

No description available.

Monounsaturated fatty acids (MUFA) have been viewed as either beneficial or neutral with respect to health; however, recent evidence suggests that MUFA may be associated with obesity and cardiovascular disease. Sex differences in MUFA composition have been reported in both rats and humans that may be mediated by sex hormones. Therefore, differences in fatty acid and enzyme expression were examined in male and female rats. HepG2 cells treated with 17β-estradiol, progesterone and testosterone (0, 10, 30 and 100 nM), and ovariectomized female rats with hormone implants (sham, no treatment, estradiol, progesterone, and estradiol plus progesterone) examined the role of sex hormones in MUFA metabolism. MUFA concentrations were determined by gas chromatography. The mRNA and protein expression of stearoyl-CoA desaturase and elongase 6, key enzymes involved in MUFA biosynthesis, were measured by real-time PCR and immunoblotting, respectively. Elongase 6 protein expression was higher in females as compared with males, increased with estradiol and progesterone treatment of HepG2 cells, and was higher in ovariectomized rats treated with estradiol. Elongase 6 expression was also decreased in HepG2 cells treated with testosterone. In contrast, the expression of stearoyl-CoA desaturase did not appear to be associated with sex or sex hormones in HepG2 cells, although ovariectomized rats treated with estradiol plus progesterone had increased stearoyl-CoA desaturase protein levels compared with sham controls. Sex differences and differences after hormonal treatments were observed in the fatty acid concentrations of MUFA and immediate MUFA substrates including 16:0, 16:1n-7, 18:0, 18:1n-7 and 18:1n-9. These differences in MUFA are consistent with the changes in elongase 6 expression. The effect of sex and hormone status on elongase 6 has not been previously examined, but these results suggest elongase 6 is an important factor in determining MUFA composition. These sex and hormonal differences in MUFA composition may contribute to sex differences in obesity and cardiovascular disease. Further work examining other factors involved in MUFA composition including oxidation, synthesis of complex lipids and the effect of diet is required.

Two methods for the estimation of non-esterified fatty acids in plasma were evaluated. An attempt was made to obtain a reliable micro-technique to estimate these acids in blood fractions. The titrimetric method of Trout et al. was satisfactory in the analyses of pure fatty acids and fatty acids added to serum. In the analyses of palmitic and stearic acid solutions, the mean values ranged from 95 to 115 percent of actual values. The mean recovery of palmitic acid added to a serum was 110 percent. The reproductibility of the method was fair in replicate analyses of three standard sera on two to four different days. The mean values determined for Serum A were 645, 653, 641, and 605; for Serum B, 587 and 587; and for Serum C, 565, 571 and 533 μEq per liter of serum. The colorimetric micro-method of Mendelsohn was also satisfactory in the analyses of pure fatty acids, fatty acids added to a serum, and a fatty acid as a component of standard lipid mixtures. In the analyses of palmitic, stearic, and oleic acid solutions, the mean values ranged from 97 to 118 percent of actual values. The recoveries of palmitic and oleic acids added to a serum ranged from 81 to 111 percent in four different experiments. In the determination of oleic acid from mixtures of several lipids, the recovery ranged from 95 to 107 percent. The reproductibility of the method was also fair in replicate analyses of a standard serum on 11 different days. The individual determinations ranged from 768 to 1046 μEq per liter of serum with a mean of 917. The mean values of 11 different experiments ranged from 830 to 1013 μEq per liter of serum. A comparison of methods was made by analyzing four standard sera in replicate by both methods. The values of the non-esterified fatty acids by the method of Mendelsohn were approximately twice those by the method of Trout et al. The difference was attributed to the degrees of extraction of non-esterified fatty acids and/or other acids from the serum by the two methods. The concentrations of the non-esterified fatty acids in the sera and the erythrocytes of 16 subjects of both sexes, ranging in age from 23 to 66 years, were determined by an adaptation of the colorimetric method of Mendelsohn. The concentrations in the sera ranged from 380 to 1057 μEq per liter with a mean of 800. The concentrations in the erythrocytes were consistently higher than those in the serum for all the subjects and ranged from 552 to 1919 μEq per liter with a mean of 1362. / Graduation date: 1965

Rainbow trout were fed semi-purified diets containing cyclopropenoid fatty acids, and the biological effects of these acids were investigated. These fatty acids occur naturally in cottonseed oil and have been implicated in a large number of physiological disorders. Included in this study was an investigation of the pattern of deposition of cyclopropenes per se in trout tissue lipids, as well as the effect of these cyclopropenes on the deposition of other fatty acids. Other effects such as growth, liver size and histology were also noted. The ingestion of methyl sterculate, 2-octyl-1-cyclopropene-1- octanoic acid, by rainbow trout resulted in the deposition of intact cyclopropene in the body tissue. The accumulation in both the muscle and depot lipid reached a level approximately equivalent to that in the diet. This cyclopropene existed as the unaltered sterculate in the tissue triglycerides as shown by GLC analysis and was approximately equal to that predicted by the Halphen determination. A method was developed whereby trout liver lipid could be quantitatively analyzed for CPFA using a modified Halphen color reaction. This method was limited, however, by the small amounts of lipid normally available in trout liver. Ingestion of CPFA by rainbow trout resulted in reduction of growth. This effect was characterized by a large growth suppression early in the feeding period followed by a more normal pattern of gain. Dietary levels of 100 ppm and 200 ppm methyl sterculate resulted in identical effects. Livers from trout fed CPFA were typically enlarged and very firm as compared to normal trout livers. They also displayed a marked lack of pigmentation. Histological examination revealed extreme damage due to increased fatty infiltration and deposition. This phenomenon appeared to be most extreme during the early stages of feeding. Dietary cyclopropenoid fatty acids induced certain changes in the pattern of fatty acid deposition in rainbow trout. This alteration was characterized by a rapid increase in the concentration of stearic acid in the tissue, which resulted in a change in the ratio of stearic to oleic acid. A similar but less pronounced effect was also observed with palmitic acid and palmitoleic acid. The liver triglycerides of trout fed CPFA for an extended period also contained less 22:6w3 than normal. When these fish were fed a CPFA-free control diet their liver lipids returned to normal within 30 days. / Graduation date: 1968

Graduation date: 1979

Graduation date: 1978

Atheroma, heart attacks and strokes continue to be a major cause of morbidity and mortality in our community. Atherosclerosis is a chronic inflammatory vascular disease, characterised by thickening of the vascular wall due to lipid accumulation, infiltration by circulating monocytes and T cells and proliferation of smooth muscle cells. Leukocyte adherence to the blood vessel wall is promoted by the up-regulation of cell adhesion molecules (CAM) by atherogenic substances such as tumour necrosis factor (TNF-α) and oxidised low density lipoprotein (oxidised-LDL). Recently our group has synthesised a novel polyunsaturated fatty acid, β-oxa 23:4n-6 which inhibits CAM up-regulation in blood vessel walls. It was therefore the objective of this thesis to determine whether this fatty acid protects against atherosclerosis. Advantage was taken of an experimental model of this disease, the apoE deficient mouse (apoE [superscript -/-]) which spontaneously develop atherosclerosis. To assist our studies on MP3, we established an appropriate classification of different stages of atherosclerotic lesions and defined the kinetics of development of the disease in this model. By examining of the sections at the level of aortic roots the atherosclerotic lesions were classified into six categories. This classification was based on the histological characteristics of the plaque component including the degree of macrophage infiltration and foam cells formation, the presence of cholesterol clefts and confluent lipid cores, calcification and ossification, the composition of the fibrous cap, the media involvement and the incipient/actual aneurysm formation and inflammation, including neutrophils. Kinetics of plaque development under the influence of a high fat and high cholesterol diet followed an exponential relationship of y= -e [ superscript -x ]. The asymptotic characteristic of this lesion development was however a function of compensatory aortic enlargement which accompanied the increase in lesion development and size. Thus it is concluded that the level of atherosclerosis needs to be gauged by the size of the lesion per se. This may be particularly important for the assessment of anti-atherogenic effects of drugs. Therefore attempts to develop a quantitative system to assess plaques revealed that expression of plaque size as % of occupation of blood vessel had limitations. Using this model we were able to demonstrate that injections of the novel polyunsaturated fatty acid, MP3 led to a significant reduction/inhibition (70%) of plaque area and a corresponding 60% inhibition of aortic size. As expected this inhibition was not as evident when results were expressed as % of aortic lumen size. The results also suggested that protection by MP3 was dependent on conditions which promoted increased uptake into tissues by, for example, preloading animals with MP3 prior to commencing the high fat high cholesterol diet. The protective effects of MP3 are consistent with a role for the activation of the transcriptional factor, NFkB and up-regulation of cell adhesion molecules in this disease, and the ability of MP3 to inhibit these targets. Thus the objective of this research has been achieved and the hypothesis proven. / Thesis (M.Med.Sc.)--Univesity of Adelaide, School of Paediatrics & Reproductive Health, 2005.