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The incorporation of [[sup 14]C]elaidic acid (trans18 : 1(n-9)) in phosphatidylcholine and phosphatidylethanolamine molecular species in isolated rat liver cells has been studied, and the results compared with the incorporation, previously published (B. Woldseth et al. Biochim Biophys Acta 1993;1167:296-302), of [[sup 14]C]palmitic acid (16 : 0) and [[sup 14]C]stearic acid (18 : 0) and with that of [[sup 14]C]oleic acid (cis18 : 1(n-9)). The pattern of incorporation in phospholipid molecular species is similar to that of [[sup 14]C]stearic acid and different from that of [[sup 14]C]palmitic acid. In phosphatidylcholine [[sup 14]C]trans18 : 1-18 : 2 and [[sup 14]C]trans18 : 1-20 : 4 were the most abundant species, and in phosphatidylethanolamine [[sup 14]C]trans18 : 1-20 : 4 was the predominant species. With increasing concentration of [[sup 14]C]elaidic acid increasing amounts of [[sup 14]C]trans18 : 1-[[sup 14]C]trans18 : 1 were found. The total incorporation in phospholipids was less than that of [[sup 14]C]stearic acid, but more than that of [[sup 14]C]palmitic acid. The distribution in percent of [[sup 14]C]elaidic acid in phospholipid classes was 8.8% in phosphatidylinositol, 1.8% in phosphatidylserine, 59.1% in phosphatidylcholine and 30.3% in phosphatidylethanolamine with 0.1 & mmol l[sup -1] substrate concentration. More [[sup 14]C]elaidic acid than [[sup 14]C]palmitic acid or [[sup 14]C]stearic acid was oxidized. The incorporation in phospholipids of [[sup 14]C]elaidic acid was very different from that of [[sup 14]C]oleic acid. The main species with [[sup 14]C]oleic acid were 16 : 0-[[sup 14]C]cis18 : 1 in phosphatidylcholine, and [[sup 14]C]cis18 : 1-20 : 4 in phosphatidylethanolamine. In some experiments [[sup 14]C]18 : 2(n-6) was incubated together with unlabelled elaidic or unlabelled trans-vaccenic acid (trans18 : 1(n-7)). In these experiments, more trans18 : 1-18 : 2 was formed from elaidic acid than from trans-vaccenic acid, especially in phosphatidylethanolamine. [ABSTRACT FROM AUTHOR]

This work tests the hypothesis that the marine algal toxin yessotoxin (YTX) can trigger ribotoxic stress response in L6 and BC3H1 myoblast cells. YTX exposure at a concentration of 100 nM displays the characteristics of a ribotoxic stress response in such cells. The exposure leads to activation of the p38 mitogen-activated protein kinase, the stress-activated protein kinase c-jun, and the double-stranded RNA-activated protein kinase (PKR). YTX treatment also causes ribosomal RNA cleavage and inhibits protein synthesis. These observations support the idea that YTX can act as a ribotoxin., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In both man and animals, inflammatory changes in the pancreas often occur with disturbances in lipid metabolism, including hypertriglyceridemia and an excess of free fatty acids. Hyperlipoproteinemia type I is a human condition caused by a deficiency of lipoprotein lipase. A similar metabolic disturbance that occurs in mink is of considerable comparative interest, as it is also followed by pancreatitis. Pancreatic lesions in hyperlipoproteinemic mink included overt variably sized nodules with hemorrhage and necrosis. These lesions began as intralobular necrosis of exocrine cells and progressed to total lobular destruction, with eventual involvement of interlobular tissue. Remnants of epithelial cells and lipid-filled macrophages were seen in necrotic areas, along with other types of inflammatory cells scattered in a lipid-rich exudate. Granulation tissue developed rapidly in necrotic areas. Additional observations included ductal proliferation, replacement of epithelial cells with fat, and mural arterial thickening, most conspicuously with vacuolated cells and endothelial proliferation. Extravasation of lipid-rich plasma is thought to be a major intensifier of the inflammatory response.

In the familial form of hyperlipoproteinaemia type I of mink (Mustela vison), mesenteric lipogranulomas are common findings in longstanding cases. Patho-morphological studies of early stages indicated that these lipogranulomas arose from stagnant chyle. The composition of fatty acids of a newly formed mesenteric granuloma was determined, together with fatty acids in liver, plasma and the feed. The results supported the pathological observations, as the fat of the granuloma differed from that of the liver and plasma, and contained only small amounts of the endogenous arachidonic acid, while the exogenous eicosenoic acid was present in amounts comparable with the dietary fat.

Objective: We assessed the effect of a cholesterol-lowering diet on maternal, cord, and neonatal plasma lipids and pregnancy outcome., Study Design: Nonsmoking white women with singleton pregnancies (n = 290), aged 21 to 38 years, and with no previous pregnancy-related complications, were randomized to either continue their usual diet or to adopt a diet that promoted fish, low-fat meats and dairy products, oils, whole grains, fruits, vegetables, and legumes from gestational week 17 to 20 to birth., Results: Maternal total and low-density lipoprotein cholesterol levels were lowered in the intervention compared with the control group (P < .01). Lipid levels in cord blood and in neonates born to mothers in the intervention versus the control groups did not differ. In the intention-to-treat cohort 1 (0.7%) of 141 women in the intervention group versus 11 (7.4%) of 149 women in the control group delivered before 37 weeks (RR 0.10; 95% CI 0.01-0.77). The incidence of other pregnancy complications and birth weight was similar in both groups., Conclusion: A cholesterol-lowering diet may modify maternal lipid levels but not cord and neonatal lipids. The marked observed effect of this diet on the reduction of preterm delivery in low-risk pregnancies should encourage future larger studies to clarify the role of such a diet in the prevention of preterm birth.

Much evidence points to a relationship among kidney disease, lipoprotein metabolism, and the enzyme lipoprotein lipase (LPL), but there is little information on LPL in the kidney. The range of LPL activity in the kidney in five species differed by >500-fold. The highest activity was in mink, followed by mice, Chinese hamsters, and rats, whereas the activity was low in guinea pigs. In contrast, the ranges for LPL activities in heart and adipose tissue were less than six- and fourfold, respectively. The activity in the kidney (in mice) decreased by >50% on food deprivation for 6 h without corresponding changes in mRNA or mass. This decrease in LPL activity did not occur when transcription was blocked with actinomycin D. Immunostaining for kidney LPL in mice and mink indicated that the enzyme is produced in tubular epithelial cells. To explore the previously suggested possibility that the negatively charged glomerular filter picks up LPL from the blood, bovine LPL was injected into rats and mice. This resulted in decoration of the glomerular capillary network with LPL. This study shows that in some species LPL is produced in the kidney and is subject to nutritional regulation by a posttranscriptional mechanism. In addition, LPL can be picked up from blood in the glomerulus.

To gain insight into the possible role of mannose-binding lectin (MBL) in HIV infection, we analyzed serum levels and the functional complement activation capacity of MBL in different clinical stages of HIV infection during cross-sectional analysis (n = 62) and longitudinal testing (n = 23) as well as during highly active antiretroviral therapy (HAART) (n = 40). The results were correlated with serum levels of C-reactive protein (CRP). Our main findings were as follows. MBL levels and the capacity of complement activation by the MBL pathway were increased in HIV-infected patients with advanced clinical disease as shown in both cross-sectional analysis and longitudinal testing. There was no "normalization" of these parameters during HAART. In fact, MBL levels increased during therapy, and this increase was associated with a good virologic response. Although both MBL and CRP are regarded as acute-phase proteins, no correlation was seen between these proteins. Thus, the notably diverse patterns of MBL responses among patients with different clinical courses and treatments suggest that MBL and complement activation by the MBL pathway could be involved in the pathophysiology of HIV infection. It is not inconceivable that the net effects of MBL responses may vary in different clinical settings.

Background: Proteinuria is an indicator of renal disease. Measurement of protein excretion is important for diagnosis and follow-up of renal disease, but measuring 24-hour protein excretion is a cumbersome procedure., Material and Methods: A simplified validated method for measuring excretion is obtained by measuring urine protein/creatinine concentration in a spot urine sample., Results: We have implemented such ratios for clinical routine measurements of proteinuria at Rikshospitalet University Hospital in Oslo. Whenever protein or albumin in urine is requested, the laboratory also measures urine creatinine and reports the ratio in mg protein/mmol creatinine. 24-hour excretion is approximately 10 times the ratio. The rationale for using the ratio is given and proteinuria pathophysiology and potential risks and treatment options are discussed., Interpretation: Our experience is that use of the urine protein/creatinine ratio is a significant improvement. Measurements are now routinely made whereas quantification was rarely performed when 24-hour urine samples were used. We recommend that physicians and laboratories implement the use of this ratio in their daily routines.

The oxidation of the fatty acid [1-(14)C]22:4n-6 was studied in isolated hepatocytes. Labeled acetate was the main acid soluble product identified by HPLC after short incubation periods. At low substrate concentrations and longer incubations [(14)C]acetate was gradually replaced by labeled beta-hydroxybutyrate, acetoacetate and oxaloacetate/malate. Preincubation with 2-tetradecylglycidic acid (TDGA), an inhibitor of mitochondrial fatty acid oxidation, did not reduce the oxidation but acetate was the only product recovered. TDGA also strongly inhibited the metabolism of added [1-(14)C]acetate to mitochondrial oxidation products. During the preparation procedure of hepatocytes the cellular L-carnitine concentration was decreased but it was restored after preincubation with L-carnitine. With low [1-(14)C]22:4n-6, concentrating a low level of [(14)C]acetate and high levels of labeled mitochondrial oxidation products were recovered after preincubation with L-carnitine. A small amount of [(14)C]acetylcarnitine was also detected under this incubation condition. The results suggest that a significant part of labeled acetyl groups from the peroxisomal oxidation of [1-(14)C]22:4n-6 is transported to the mitochondria as free acetate. Moreover, the results also suggest that L-carnitine at physiological concentrations may facilitate the transport of part of the acetyl groups from peroxisomes to mitochondria as acetylcarnitine. However, the possibility that an increased cellular L-carnitine concentration may stimulate oxidation of [1-(14)C]22:4n-6 in mitochondria could not be excluded.

Unlabelled: Margarine leads to lower total and LDL cholesterol (LDL-C) levels than butter but may contain trans fatty acids that increase atherogenic lipids. A food company has used data concerning the cholesterolemic effects of individual fatty acids, including trans fatty acids, to develop a commercially available and virtually trans-free margarine., Objective: The effect of this novel margarine on serum lipids and lipoproteins was compared with that of butter in free-living, hypercholesterolemic subjects., Design and Setting: A two-period, outpatient cross-over trial at a university hospital lipid clinic., Subjects: The study involved 77 subjects, and was completed by 53 men and 19 women aged 35-65 years with total serum cholesterol levels of between 6.0 and 7.9 mmol/L., Intervention: Two 23-day regimens, separated by a 4-week washout period, included individualised dietary prescriptions supplemented with butter or margarine designed to provide 15% of total dietary energy., Results: In comparison with butter, margarine intake lowered total and LDL-C levels by respectively 11.1% (99% CI: 8.1-14.1) and 11.3% (99% CI: 7.6-15.1). The reduction in LDL-C was < 3% in nearly one-fifth of the subjects despite appropriate changes in serum triglyceride fatty acids. Of the tested clinical and demographic variables, only the percentage of energy obtained from saturated fat during the margarine intake period was associated with dietary responsiveness (explaining 12% of the variation; p < 0.01)., Conclusion: Our results suggest that a margarine designed to meet nutritional recommendations for hypercholesterolemia is more efficacious than butter in reducing atherogenic lipid levels in hypercholesterolemic subjects.

Which cell type is responsible for the high levels of very long chain polyunsaturated fatty acids in testis and whether this fatty acid pattern is a result of a local synthesis are not presently known. In this study, fatty acid conversion from 20:4n-6 to 22:5n-6 and from 20:5n-3 to 22:6n-3 was investigated in isolated rat germ cells incubated with [1-14C]-labeled fatty acids. The germ cells elongated the fatty acids from 20- to 22-carbon atoms and from 22- to 24-carbon atoms but had a low delta6 desaturation activity. Thus, little [14C]22:5n-6 and [14C]22:6n-3 were synthesized. When Sertoli cells were incubated with [1-14C]20:5n-3 for 24 h, an active fatty acid elongation and desaturation were observed. In vivo germ cells normally have a higher content of 22:5n-6 or 22:6n-3 than Sertoli cells. An eventual transport of essential fatty acids from Sertoli cells to germ cells was thus studied. Different co-culture systems were used in which germ cells were on one side of a filter and Sertoli cells on the opposite side. When isolated pachytene spermatocytes or round spermatids were added to the opposite side of a semipermeable filter, approximately 1 nmol [14C]22:6n-3 crossed the filter. Little of this was esterified in the germ cells. Similarly, in using [1-14C]20:4n-6 in identical experiments, very little [14C]22:5n-6 was esterified in germ cells on the opposite side of the filter. Although the very active synthesis of 22:5n-6 and 22:6n-3 observed in Sertoli cells suggests a transport of these compounds to germ cells, this was not experimentally determined.