Search PubMed⌕ Search

Biomedical subjects

J Bruce German

Publications and source records attributed to J Bruce German.

28 records · Page 2Linked to original sources

Unraveling lipid metabolism with microarrays: effects of arachidonate and docosahexaenoate acid on murine hepatic and hippocampal gene expression.

The functions, actions, and regulation of polyunsaturated fatty acids (PUFAs) are beginning to be unraveled. Mice were fed diets rich in either arachidonic acid, docosahexaenoic acid, or both. Liver and hippocampus tissue were then analyzed through a combined gene expression-, lipid-, and behavioral- profiling strategy. Novel hippocampal PUFA-molecular targets suggest that PUFA transcriptionally regulated genes with roles in appetite and learning.

Animals↗

Effects of natural phenolic compounds on the antioxidant activity of lactoferrin in liposomes and oil-in-water emulsions.

The effect of natural phenolic compounds on the antioxidant and prooxidant activity of lactoferrin was studied in liposomes and oil-in-water emulsions containing iron. The antioxidants tested with lactoferrin were alpha-tocopherol, ferulic acid, coumaric acid, tyrosol, and natural phenolic extracts obtained from three different extra-virgin olive oils and olive mill wastewater. The natural extracts of olive oils and mill wastewaters were composed mainly of polyphenols and simple phenolics, respectively. Lipid oxidation at 30 degrees C was determined by the formation of hydroperoxides and fluorescent compounds resulting from oxidized lipid interactions. All phenolic compounds showed synergistic properties in reinforcing the antioxidant activity of lactoferrin in lipid systems containing iron. The highest synergistic effects were observed for the phenolic extracts rich in polyphenols of extra-virgin olive oils and lactoferrin. This synergistic effect was higher in liposomes than in emulsions.

Antioxidants↗

Analysis of lipoproteins by capillary zone electrophoresis in microfluidic devices: assay development and surface roughness measurements.

The development of a new assay for lipoproteins by capillary electrophoresis in fused-silica capillaries and in glass microdevices is described in this paper. The separation of low-density (LDL) and high-density (HDL) lipoproteins by capillary zone electrophoresis is demonstrated in fused-silica capillaries with both UV absorption and laser-induced fluorescence detection. This separation was accomplished using Tricine buffer (pH 9.0) with methylglucamine added as a dynamic coating. With UV detection, LDL eluted as a relatively sharp peak with a migration time of approximately 11 min and HDL eluted as a broad peak with a migration time of 12.5 min. Fluorescence detection of lipoproteins stained with NBD-ceramide was used with the same buffer system to give comparable results. Furthermore, fluorescence staining of human serum samples yielded results similar to the fluorescently stained LDL and HDL fractions, showing that this method can be used to quantify lipoproteins in serum samples. The method was also used to detect lipoproteins in glass micro-CE devices. Very similar results were obtained in microdevices although with much faster analysis times, LDL eluted as a sharp peak at approximately 25 s and HDL as a broad peak at slightly longer time. In addition, higher resolution was obtained on chips. To our knowledge, these results show the first separation and detection of lipoproteins in a microfluidic device using native serum samples. Atomic force microscopy was used to characterize the rms surface roughness (Rq) of microfluidic channels directly. Devices with different surface roughness values were fabricated using two different etchants for Pyrex wafers with a polysilicon masking layer. Using 49% HF, the measured roughness is Rq = 10.9 +/- 1.6 nm and with buffered HF (NH4F + HF) the roughness is Rq = 2.4 +/- 0.7 nm. At this level of surface roughness, there is no observable effect on the performance of the devices for this lipoprotein separation.

Chromatography, Gel↗

Oxidative stability of fish and algae oils containing long-chain polyunsaturated fatty acids in bulk and in oil-in-water emulsions.

The oxidative stability of long-chain polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (DHA)-containing fish and algae oils varies widely according to their fatty acid composition, the physical and colloidal states of the lipids, the contents of tocopherols and other antioxidants, and the presence and activity of transition metals. Fish and algal oils were initially much more stable to oxidation in bulk systems than in the corresponding oil-in-water emulsions. The oxidative stability of emulsions cannot, therefore, be predicted on the basis of stability data obtained with bulk long-chain PUFA-containing fish oils and DHA-containing algal oils. The relatively high oxidative stability of an algal oil containing 42% DHA was completely lost after chromatographic purification to remove tocopherols and other antioxidants. Therefore, this evidence does not support the claim that DHA-rich oils from algae are unusually stable to oxidation. Addition of ethylenediaminetetraacetic acid (EDTA) prevented oxidation of both fish and algal oil emulsions without added iron and at low iron:EDTA molar concentrations. EDTA, however, promoted the oxidation of the corresponding emulsions that contained high iron:EDTA ratios. Therefore, to be effective as a metal chelator, EDTA must be added at molar concentrations higher than that of iron to inhibit oxidation of foods containing long-chain PUFA from either fish or algae and fortified with iron.

Chelating Agents↗

Toward the implementation of metabolomic assessments of human health and nutrition.

Metabolomics is emerging as an exciting post-genomic science with applications that span the scope of biotechnology and medicine. Although metabolomics is still in its infancy, it has already been used to identify the function of genes, describe the effects of toxicological, pharmaceutical, nutritional and environmental interventions, and to build integrated databases of metabolite concentrations across human and research animal populations. Metabolomics provides nutrition with an invaluable tool for determining the distributions of metabolite concentrations in humans, the relationship of these metabolite concentrations to disease, and the extent to which nutrition can modulate metabolite concentrations.

Animals↗

Effect of estrogen and 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) on plasma fatty acids of immature male chickens (Gallus domesticus).

This study investigated the effects of 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) and estrogen on plasma lipids in immature male chickens. Fatty acids were quantified in plasma collected on day 14 from chickens injected with either: Estrogen plus TCDD-1 mg estradiol cypionate /kg body wt. daily for 3 days and 50 microg TCDD/kg body wt. on day 4; Estrogen--1 mg estradiol cypionate/kg body wt. daily for 3 days and vehicle only on day 4; TCDD-vehicle only for 3 days and 50 microg TCDD/kg body wt. on day 4; or Vehicle--same volume of appropriate vehicle for 4 days. TCDD treatment alone increased the plasma concentrations of total triacylglycerides and of the specific fatty acids 14:0, 15:0, 18:0, 18:2n6, 18:3n3, 20:0, 20:1n9, 20:2n6, 20:3n6, 20:5n3 and 22:1n9, compared with vehicle treatment. The concentration of 22:6n3 was increased in all plasma lipid classes of the estrogen group compared with the vehicle group, but was not increased in the estrogen plus TCDD group. Overall, TCDD treatment alone increased plasma lipids, possibly as a result of decreased clearance or utilization; whereas estrogen plus TCDD treatment antagonized estrogen-induced increases in 22:6n3 but did not cause hyperlipidemia.

Adipose Tissue↗

Urinary excretion of catechin metabolites by human subjects after red wine consumption.

Little is known about flavonoid metabolism and excretion in man. In the present study, the urinary excretion of a major flavonoid in wine, catechin, and its metabolites, were measured after nine human subjects each consumed 120 ml red wine (RW) on one day and de-alcoholized red wine (DRW) on a separate day. Both the RW and DRW contained 120 (SEM 3) micromol catechin (35 mg). GC-MS analyses of the trimethylsilylated derivatives of catechin and 3' and 4' methylcatechin were performed before and after hydrolysis of conjugates by beta-glucuronidase and sulfatase. Baseline urine samples collected prior to wine consumption contained 0.013 (SEM 0.005) micromol catechin and metabolites. During the 8 h period following consumption of RW and DRW, 6.6 (SEM 0.9) and 5.3 (SEM 0.6) micromol catechin and metabolites were excreted in 893 (SEM 94) and 740 (SEM 101) ml urine respectively. This corresponded to 3.0-10.3% of the dose after RW and 2.1-8.2% of the dose after DRW. The amount of catechin and metabolites excreted in urine was 20% higher after RW compared with DRW (P=0.06). Catechin in all urine samples was present as metabolites and there were no differences in the proportions of individual metabolites after RW and DRW. As with other flavonoids, the fate of most ingested catechin is not yet known.

Adult↗

Bioactive components in milk.

Milk is the only biomaterial that evolved under the Darwinian selective pressure to nourish growing mammals. The purpose of this article is to review the scientific research that is using new techniques of integrating biological sequence, structure and function, to understand the innovative biology underlying the products of that evolutionary pressure. As it emerges that milk is actively communicating between the maternal mammary epithelia and the infant's gastrointestinal system, actively directing and educating the immune, metabolic and microflora systems within the infant, enhancing nutrient absorption and delivery, and conferring multiple means of protection, nutritionists are gaining a host of new molecular targets towards which to build scientific strategies for future foods and clinical applications. As new components and functions are being discovered in milk by using traditional methods and modern genomic tools, the complexities of demonstrating, and particularly in humans, the functional mechanisms behind milk's newly observed physiological benefits are becoming the next challenge of this rapidly growing field.

Animals↗

Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone.

Successful therapy for chronic diseases must normalize a targeted aspect of metabolism without disrupting the regulation of other metabolic pathways essential for maintaining health. Use of a limited number of single molecule surrogates for disease, or biomarkers, to monitor the efficacy of a therapy may fail to predict undesirable side effects. In this study, a comprehensive metabolomic assessment of lipid metabolites was employed to determine the specific effects of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone on structural lipid metabolism in a new mouse model of Type 2 diabetes. Dietary supplementation with rosiglitazone (200 mg/kg diet) suppressed Type 2 diabetes in obese (NZO x NON)F1 male mice, but chronic treatment markedly exacerbated hepatic steatosis. The metabolomic data revealed that rosiglitazone i) induced hypolipidemia (by dysregulating liver-plasma lipid exchange), ii) induced de novo fatty acid synthesis, iii) decreased the biosynthesis of lipids within the peroxisome, iv) substantially altered free fatty acid and cardiolipin metabolism in heart, and v) elicited an unusual accumulation of polyunsaturated fatty acids within adipose tissue. These observations suggest that the phenotypes induced by rosiglitazone are mediated by multiple tissue-specific metabolic variables. Because many of the effects of rosiglitazone on tissue metabolism were reflected in the plasma lipid metabolome, metabolomics has excellent potential for developing clinical assessments of metabolic response to drug therapy.

Adipose Tissue↗

Metabolomics and biochemical profiling in drug discovery and development.

Metabolomics brings a different and complementary perspective to biomedical research and therapeutic development. Metabolites are measurable, directly responsible for health, and changeable through intervention. By definition, the concentrations of metabolites are the direct reflection of metabolism, and by measuring changes in metabolite concentrations, the full range of biochemical effects induced by a therapeutic intervention can be determined. In a clinical setting, metabolomics can be used to diagnose or predict disease, stratify patient populations by their specific metabolism, or to determine the safety or efficacy of a therapeutic intervention. Metabolomics is useful in virtually all aspects of biomedical research, and it is likely to evolve into an essential component of the drug discovery and development process.

Animals↗