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Biomedical subjects

W E Lands

Publications and source records attributed to W E Lands.

At least 37 records · Page 2Linked to original sources
PubMed1991

Differential detection of plasma hydroperoxides in sepsis.

OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis. DESIGN: Exploratory, open-label study. SETTING: Critical care unit at a university medical center. PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters. Seven patients were diagnosed with pulmonary infections and five patients had intra-abdominal infections. INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient. Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase. MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005). CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma. Assays for hydroperoxides may be useful when relatively free of other tissue trauma.

Adult↗
PubMed1990

Quantitative effects of dietary polyunsaturated fats on the composition of fatty acids in rat tissues.

A method combining data on fatty acid composition into subsets is used to illustrate general relative competitive selectivities in the metabolic and transport events that maintain fatty acid compositions in tissue lipids and to minimize differences among tissues or species in the amount of individual fatty acids. Fatty acid compositions of triglycerides and phospholipids in several tissues of the rat were maintained with simple relationships between the exogenous n-3 and n-6 dietary polyunsaturated fatty acids and the endogenous n-7 and n-9 types of fatty acid. The general pattern of fatty acids in triglycerides was similar for liver, plasma and adipose tissue, averaging about 30% as saturated acids, 67% as 16- and 18-carbon unsaturated acids and only about 2% as 20- and 22-carbon highly unsaturated acids. The tissues maintained a linear relationship between the amount of 18-carbon polyunsaturated fatty acids in the diet and in the tissue triglycerides, with the proportionality constant for 18:3n-3 being 60% of that for 18:2n-6. The total phospholipids of liver, plasma and red blood cells maintained about 45% of the fatty acids in the form of saturated fatty acids and 20-30% as 20- and 22-carbon highly unsaturated fatty acids irrespective of very different proportions of n-3, n-6 and n-9 types of fatty acids. In all three tissues, the 20-carbon highly unsaturated fatty acids of the n-3, n-6 and n-9 type were maintained in a competitive hyperbolic relationship with apparent EC50 values for dietary 18:2n-6 and 18:3n-3 near 0.1% of dietary calories. The consistent quantitative relationships described in this study illustrate an underlying principle of competition among fatty acids for a limited number of esterification sites. This approach may be useful in predicting the influence of diet upon tissue levels of the substrates and antagonists of eicosanoid biosynthesis.

Adipose Tissue↗
PubMed1990

Rapid analysis of fatty acids in plasma lipids.

A rapid and convenient procedure for the quantitative determination of the fatty acid composition of plasma lipids is described. Human plasma was applied directly to the preadsorbent zones of thin-layer silica gel plates with added antioxidant, internal standards and carriers. The thin-layer chromatography (TLC) plates were partially developed with methanol followed by chloroform/methanol (1:1, v/v), and then they were fully developed in hexane/diethyl ether/acetic acid (80:20:1, v/v/v) to separate the major classes of lipids. Silica gel from regions containing the separated lipids was scraped into screw-capped tubes and treated with boron trifluoride-methanol prior to gas chromatography. The method of direct application to TLC plates gave yields and compositions of fatty acids very similar to the method of applying extracted plasma lipids. This relatively simple method is suitable for analyzing the fatty acids in plasma lipids from a 50 microliter finger-tip blood samples from an individual, and it may be useful in wide-scale screening of different individuals to estimate the relative amounts of ingested polyunsaturated fatty acids.

Chromatography, Gas↗
PubMed1990

Differences between arterial and mixed venous levels of plasma hydroperoxides following major thoracic and abdominal operations.

Fatty acid hydroperoxides in the plasma of 18 patients who were undergoing normal postoperative periods following major thoracic or abdominal operations were measured by using a sensitive assay based upon the activation of the cyclooxygenase activity of prostaglandin H synthase. Following major thoracic operations of nine patients, the mean difference between the arterial (0.49 +/- 0.13 microM, mean +/- S.E.M.) and mixed venous (-0.09 +/- 0.12 microM) level of hydroperoxide was 0.58 +/- 0.13 microM (p less than 0.01). In marked contrast to this result, major abdominal operations of nine patients led to a mean difference between the arterial (-0.19 +/- 0.16 microM) and mixed venous (0.46 +/- 0.08 microM) hydroperoxide levels of -0.65 +/- 0.17 microM (p less than 0.01). Both pulmonary and intraabdominal tissues appear capable of generating significant amounts of fatty acid hydroperoxide in response to standard surgical procedures. The A-MV differences suggest that the blood-borne hydroperoxides were rapidly cleared from the circulation by tissue capillary beds.

Abdomen↗
PubMed1990

Changing dietary patterns.

Previously traditional dietary patterns in Japan are no longer typical. The current changing conditions provide an opportunity to examine more closely some important health conditions associated with the changed lifestyle and concentrations of dietary total fat and saturated fatty acid, and the ratio of n-3 to n-6 polyunsaturated fatty acids in the diet.

Diet↗
PubMed1989

n-3 fatty acids as precursors for active metabolic substances: dissonance between expected and observed events.

It may be hypothesized that many diseases are associated with an overproduction of eicosanoids from the n-6 acid, arachidonic acid (20:4n-6), and the formation and function of these n-6 eicosanoids can be antagonized by dietary n-3 fats. This hypothesis provides a basis for evaluating the benefits and risks of including various amounts of n-3 and n-6 fats in the diet. Understanding the impact of dietary polyunsaturated fats leads inevitably to a reappraisal of what is 'normal' in terms of what is typical and what is desirable for the fatty acid composition of tissue lipids, the magnitude of eicosanoid-mediated responses, and the frequency and severity of certain diseases.

Animals↗
PubMed1988

A comparison of dietary fish oil and corn oil in experimental colorectal carcinogenesis.

Rats fed either fish oil (n = 16) or corn oil (n = 16) in calorically and nutritionally balanced diets were injected with 1,2-dimethylhydrazine, which is a colorectal specific carcinogen; differential colorectal tumor induction was then measured. In addition, plasma peroxide concentrations were measured in rats in each dietary group as well as in a group receiving a low-fat diet, either with or without prior carcinogen treatment (n = 3 for each of the 6 groups). Tumor incidence did not differ between groups fed corn oil and fish oil. Tumor yield in the left colon was significantly lower in rats fed fish oil (p = 0.0499). Total colorectal tumors induced were also fewer in the rats fed fish oil (p = 0.065). Plasma peroxide concentrations were difficult to interpret because of the wide variation within groups. The data on tumor yield in the left colon support the hypothesis that a diet rich in n-3 fatty acids, which are found in fish oil, may be less supportive of colorectal tumor development than a diet rich in n-6 fatty acids, which is found in corn oil. However, the mechanism by which fish oil decreases tumor induction is still unknown.

1,2-Dimethylhydrazine↗
PubMed1988

Discriminations among unsaturated fatty acids.

Several different systems in which unsaturated fatty acids selectively serve an important role provide evidence that the enzymes that select the acyl chains can discriminate among small structural features that were not commonly regarded to be an important feature in explaining how the "good" fatty acids serve their roles. Acyltransferases placing low-melting unsaturated acids in phospholipids do not seem to select the acids for that property. Similarly, the high melting saturated acids seem to be selected for esterification by discrimination of features other than a lack of unsaturation or a high melting point. Finally, the fatty acid essential for optimal growth of young mammals, arachidonate (20:4n-6), is often converted to eicosanoids more rapidly than is compatible with a good quality of life for the adults. In contrast, the n-3 analog, eicosapentaenoate (20:5n-3), does not support such rapid growth and has been classified as non-essential, yet it may moderate the formation and function of n-6 eicosanoids in ways that permit a better chance of survival from eicosanoid-mediated disorders. As a result of attention to presumed functions, we have classified certain fatty acids by using features not actually regulating the enzymatic discriminations by which Nature functions. Such dissonance seems to assure that stories we have been providing about the "appropriateness" of certain membrane lipid structures will be altered by future researchers evaluating the action of lipids in the kinetics of the life and death of a cell.

Acyl Coenzyme A↗
PubMed1987

Distribution of dietary trans-octadecenoate among acyl-CoA and other lipid fractions of rat liver and heart.

Groups of rats were fed diets containing 10% of either corn oil, partially hydrogenated soybean oil, or a mixture of the two. The partially hydrogenated oil contained a high level of trans-octadecenoate and a low level of linoleate, and all diets were adjusted to contain similar levels of cis-octadecenoate. The fatty acid compositions of five tissue lipid fractions from liver and heart (non-esterified fatty acids, acyl-CoA, diacylglycerols, triacylglycerols and phospholipids) were analyzed to measure the effect of the dietary supply on the accumulation of trans-octadecenoates and other fatty acids at different steps of glycerolipid synthesis. Although trans-octadecenoate was increased in all of the lipid fractions when the dietary supply was increased, the accumulation did not exceed 15% of the acyl chains in any of the lipid pools even when the dietary trans acid accounted for 46% of the fatty acids supplied in the diet. The trans-octadecenoate accumulated in a similar manner in the lipids of both liver and heart, and the amounts found in the acyl-CoA esters of both tissues were relatively low compared to the diet. A high dietary supply of trans-octadecenoate appeared to diminish the relative content of stearate in the acyl-CoA and phospholipid fractions. The level of cis-octadecenoate maintained in tissue phospholipids was similar to that in the acyl-CoA fractions, whereas the trans-octadecenoate content in phospholipids more closely resembled that in the diacylglycerols. Normal proportions of arachidonate were maintained in the tissue phospholipids during high intake of trans acids, even though lower levels were observed in the acyl-CoA and diacylglycerols of liver.

Acyl Coenzyme A↗
PubMed1987

Constraints on prostaglandin biosynthesis in tissues.

The formation of prostaglandins by prostaglandin H synthase can be limited by the availability of the fatty acid substrate or the hydroperoxide activator and also by a self-catalyzed inactivation associated with the oxygenation reaction. Each pmol of synthase appeared able to form only about 1300 pmol of prostaglandin from arachidonate before it was inactivated. This extent of synthesis was not diminished when substrate fatty acid was complexed with cytosolic proteins even though the velocity of the oxygenation reaction was greatly decreased by the lower availability of substrate acid. When the availability of hydroperoxide activator was decreased by added glutathione peroxidase, the extent of oxygenation per mol of synthase was decreased irrespective of the amount of cytosolic protein present. Approximately 65% of the total prostaglandin synthesis by homogenates was suppressed with a glutathione peroxidase to prostaglandin H synthase ratio of about 90. The remaining prostaglandin synthetic activity was more resistant, being completely suppressed only when the ratio of peroxidase to synthase exceeded 750. The overall ratio of glutathione peroxidase (peroxide-removing) capacity to prostaglandin synthetic (peroxide-forming) capacity in selected tissues ranged from over 1800 in rat liver to less than 30 in leukocytes. A comparison between the daily urinary output of prostaglandin metabolites and tissue prostaglandin synthetic capacity suggested that prostaglandin H synthase inactivation along with glutathione peroxidase suppression of the extent of prostaglandin synthase may be important in limiting prostaglandin biosynthesis within cells.

Animals↗