Biomedical subjects

J Bruce German

Publications and source records attributed to J Bruce German.

14 recordsLinked to original sources

PubMed2003

Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil.

BACKGROUND: Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus. METHODS: Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F(2-alpha) and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids. RESULTS: Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1+/-3 vs. 6.0+/-1.1 ml/min in the nonsupplemented group; P<0.001); urinary PGF(2-alpha) excretion was also highest in the JO group (328+/-23 pg/mL, P<0.001 vs. the nonsupplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7+/-0.6% and 3.1+/-0.4%, respectively) and FO- (8.1+/-0.7% and 2.8+/-0.6%, respectively) treated animals. CONCLUSIONS: JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF(2-alpha) excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

Animals↗

PubMed2003

PASSCLAIM - Diet-related cardiovascular disease.

Cardiovascular disease (CVD) has a multifactorial aetiology and many potential risk markers are known. As it was not feasible to discuss all markers and their possible interactions in relation to all aspects of CVD, selections had to be made in this paper. In the context of claims and functional foods, emphasis was placed on those aetiological processes and risk markers that have been shown previously to be modified by diet: lipid and lipoprotein metabolism, haemostatic function, oxidative damage, homocysteine metabolism, and blood pressure. Except for methodological and biological characteristics of these biomarkers, their relationships with the risk of CVD are discussed. For LDL and HDL cholesterol, fasting triacylglycerol, homocysteine, and blood pressure well-validated, easy applicable, and generally accepted biomarkers exist. For haemostatic function and oxidative damage validation of markers with respect to CVD or intermediate clinical markers is recommended. For diet-related CVD, however, the ultimate question is whether changes in the biomarker are truly related to changes in risk. Only for LDL cholesterol and blood pressure does consensus exist among scientists for a possible application as enhanced function claims. For HDL, triacylglycerol, and homocysteine, and in particular for haemostatic function and oxidative damage, however, formal proof is lacking that diet-induced changes in these biomarkers alter the risk of CVD. At the same time, it should be emphasised that CVD is multifactorial. Therefore it does not seem justified that a change in one particular biomarker is enough evidence to substantiate a claim. There are examples of food components or drugs that one biomarker is changed in a favourable way, but at the same time another biomarker is changed in an unfavourable way. Therefore, studies to further validate generic predictors for the CVD risk should be initiated.

Animals↗

PubMed2003

Genomics and metabolomics as markers for the interaction of diet and health: lessons from lipids.

Foods are not purified compounds acting on single molecular targets, but complex mixtures of molecules that modulate many biochemical pathways simultaneously. Diet affects the probability of developing various diseases. Nevertheless, specific recommendations for individual diets are not simple. Recommending nutrient intakes above and beyond those needed to provide adequacy requires scientific knowledge and regulatory scrutiny to ensure the efficacy and safety even of essential nutrients. Designing a diet to improve metabolic health is a bold and ambitious goal. It is possible to design foods that will alter metabolism, but what change will make everyone who is otherwise healthy even healthier? Changing one aspect of metabolism to lower the risk of one disease does not improve overall health if it comes at the expense of disrupting another aspect of metabolism that increases the risk of another disease. This issue has: 1) frustrated nutritional recommendations that could provide benefits to the health of large subsets of the population, 2) caused the recall of drugs with many beneficial effects and 3) caused harm by implying that single nutrients/foods could be healthy for everyone. An individualized system for metabolic assessment would establish the efficacy and safety of nutrients such as amino acids or fatty acids when these are designed to be consumed at levels providing improved metabolic health. The need to document the lack of an adverse effect of a food or drug on physiology necessitates a global, i.e. metabolomic approach.

Animals↗

PubMed2002

Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression.

BACKGROUND: The functions, actions, and regulation of tissue metabolism affected by the consumption of long chain polyunsaturated fatty acids (LC-PUFA) from fish oil and other sources remain poorly understood; particularly how LC-PUFAs affect transcription of genes involved in regulating metabolism. In the present work, mice were fed diets containing fish oil rich in eicosapentaenoic acid and docosahexaenoic acid, fungal oil rich in arachidonic acid, or the combination of both. Liver and hippocampus tissue were then analyzed through a combined gene expression- and lipid- profiling strategy in order to annotate the molecular functions and targets of dietary LC-PUFA. RESULTS: Using microarray technology, 329 and 356 dietary regulated transcripts were identified in the liver and hippocampus, respectively. All genes selected as differentially expressed were grouped by expression patterns through a combined k-means/hierarchical clustering approach, and annotated using gene ontology classifications. In the liver, groups of genes were linked to the transcription factors PPARalpha, HNFalpha, and SREBP-1; transcription factors known to control lipid metabolism. The pattern of differentially regulated genes, further supported with quantitative lipid profiling, suggested that the experimental diets increased hepatic beta-oxidation and gluconeogenesis while decreasing fatty acid synthesis. Lastly, novel hippocampal gene changes were identified. CONCLUSIONS: Examining the broad transcriptional effects of LC-PUFAs confirmed previously identified PUFA-mediated gene expression changes and identified novel gene targets. Gene expression profiling displayed a complex and diverse gene pattern underlying the biological response to dietary LC-PUFAs. The results of the studied dietary changes highlighted broad-spectrum effects on the major eukaryotic lipid metabolism transcription factors. Further focused studies, stemming from such transcriptomic data, will need to dissect the transcription factor signaling pathways to fully explain how fish oils and arachidonic acid achieve their specific effects on health.

Journal Article↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗