Effect of dietary fats rich in lauric, myristic, palmitic, oleic or linoleic acid on plasma, hepatic and biliary lipids in cholesterol-fed hamsters

Effects of different dietary fats on plasma, hepatic and biliary lipids were determined in male golden Syrian hamsters (Mesocricetus auratus) fed on purified diets for 7 weeks. Diets were made by blending different fats containing characteristic fatty acids: butter (14:0 + 16:0), palm stearin (16:0), coconut oil (12:0 + 14:0), rapeseed oil (18:1), olive oil (18:1) and sunflowerseed oil (18:2). In all diets except the sunflowerseed oil diet dietary 18:2 was held constant at 2% energy. Total fat supplied 12% of energy and cholesterol was added at 4 g/kg diet. Plasma cholesterol and triacyglycerol concentrations were increased by dietary cholesterol. After 7 weeks, plasma cholesterol concentrations were highest with the palm stearin, coconut oil and olive oil diets (8.9, 8.9 and 9.2 mmol/l) and lowest with the rapeseed oil and sunflowerseed oil diets (6.7 and 5.5 mmol/l) while the butter diet was intermediate (8.5 mmol/l). Hepatic cholesterol concentration was highest in hamsters fed on the olive oil diet and lowest with the palm stearin diet (228 v. 144 mumol/g liver). Biliary lipids, lithogenic index and bile acid profile of the gall-bladder bile did not differ significantly among the six diets. Although the gallstone incidence was generally low in this study, three out of 10 hamsters fed on the palm stearin diet developed cholesterol gallstones. In contrast, no cholesterol gallstones were found with the other diets. Rapeseed and sunflowerseed oils caused the lowest plasma cholesterol and triacyglycerol concentrations whereas olive oil failed to demonstrate a cholesterol-lowering effect compared with diets rich in saturated fatty acids. Since 18:2 was kept constant at 2% of energy in all diets, the different responses to rapeseed and olive oils could possibly be attributed to their different contents of 16:0 (5.6% v. 12.8% respectively). Other possible explanations are discussed.     

Tissue specific-distribution and metabolism of vitamin A are affected by dietary protein levels in rats

The prevalence of human immunodeficiency virus (HIV) in adolescents is difficult to assess as few adolescents consent to testing. This prospective study characterized urban youth requesting HIV testing at two types of health settings, inner-city school-based and hospital-based clinics. Data were obtained on 1652 inner-city youths aged 13 to 19 years who consented to individualized HIV counseling and testing from January 1993 to January 1994. Identified risks for HIV included sexual activity, sexually transmitted disease (STD) history, and substance use by self-report during a confidential structured interview. Data were analyzed using chi-squared analysis. Of the 1652 youth who were counseled, 1602 were from hospital-based clinics. A total of 827 (50%) requested HIV testing. Females accounted for the majority of youth who underwent counseling (79%) and requested HIV testing (75%). However, once counseled, males were more likely to be tested. Risk factors differed by gender; females were more likely to report STDs and marijuana use, and males more likely to report alcohol and cocaine use. These results indicate a need to identify developmentally appropriate methods to educate and counsel youth about HIV that will lead to more youth willing to be tested. School-based clinics may provide easier access than traditional health models for confidential HIV services.     

Incorporation of 1-C14 palmitic acid into liver lipids of rats in different hormanal states

Adrenalectomy and/or cortisol-induced variations in the in vivo and in vitro incorporation of 14C-palmitic acid 1 into the different fractions of rat liver lipids were studied. The different fatty acids incorporations follow analogous patterns in every hormonal state in vitro. Incorporation rate is faster in normal animals, but adrenalectomy or the administration of cortisol produces a marded delay. Cortisol does not modify the anomalism observed in the adrenoprival state. In vivo, the incorporation of palmitic acid into the different liver lipids--for the same hormonal state--does not follow the same pattern.     

Arachidonic and palmitic acid utilization in aged rat brain areas

We have previously demonstrated that the arachidonic acid (20:4) incorporation into brain lipids differs according to the age of the animals used and the experimental conditions adopted. These differences led to a further investigation of arachidonic acid uptake in both aged and adult rat brains, its transformation into CoA derivatives, its incorporation into diacyl-glycerols and polar lipids, and finally its oxidation to CO2. These metabolic parameters were then compared with those obtained after using the saturated fatty acid palmitate (16:0). In both cases slices or mitochondria from different brain areas of 24-month-old and 4-month-old rats were examined. The results obtained indicate that the uptake of the fatty acids into cells is not modified by age. However, the successive metabolic transformations of the acids are altered to a considerable extent. In particular, in 24-month-old animals (compared with 4-month-old rats) there is a significant decrease of 20:4 in its incorporation into lipids as well as its oxidation to CO2, while arachidonoyl-CoA content increases by about 50%. This increased amount of CoA derivative, which has a potent detergent effect, may interfere with membrane structure and affect membrane physiological functions. Furthermore, because the free arachidonate pool is maintained in a dynamic equilibrium with its esterified forms, the final result may be a perturbation of this equilibrium.     

Plasma cortisol and appetitively motivated arousal in monkeys.

Six adult male rhesus monkeys subjected to appetitive conditioning once every 48 hrs showed significantly more emotional arousal during positive- than negative-conditioning sessions. Appetitive conditioning suppressed the increase in plasma cortisol found in control conditions, and dissociation between cortisol and arousal indicated that plasma glucocorticoids are an insensitive arousal index. Previous similar findings with rats suggest that hormonal regulatory mechanisms are different for rodents and primates. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma and red cell lipids in sickle cell disease

Lipids, in particular phospholipids, are essential components of membrane systems, and the measurement of phospholipids and cholesterol in plasma and tissues is helpful in diagnosis. Phospholipids represent about 60 to 70% of total red cell (RBC) lipids, while about 25% is free cholesterol. Lipids in RBC are present in a dynamic state of equilibrium, and the RBC have the capacity for rapid exchange of lipids with plasma in several ways. The present study examined the cholesterol and phospholipid levels of plasma and erythrocytes in male patients with sickle cell anemia and in healthy male individuals of comparable age. This was performed with a view to detecting possible differences that might be related to some of the RBC abnormalities which accompany the disease. The results show that plasma lipids are significantly reduced in patients with sickle cell anemia and that RBC cholesterol was higher in sickle cell patients than in normal subjects.     

Visual evoked potentials are affected by trunk rotation in neglect patients

Steady-state visual evoked potentials (VEPs) were recorded in four patients with unilateral visuo-spatial neglect, stimulating either the left or the right hemifield. In the standard condition (head and body oriented straight ahead towards the stimulus) the left hemifield VEP was delayed. When the body was turned to the left, however, the two hemifield latencies were comparable. These results were confirmed with the transient VEP technique. No effect of trunk rotation was observed in a group of patients with left brain damage and without neglect. The results imply that the sensory afferents from neck muscles might restore the altered occipital activity and suggest that the same conditions which modulate neglect modulate VEPs latencies.     

Effects of dietary fatty acid composition on basal and hormone-stimulated hepatic lipogenesis and on circulating lipids in the rat

Thirty male rats were randomly assigned to one of three dietary groups in which the source of dietary fat was either a mixed oil, maize oil or fish oil. Effects of dietary fatty acid composition on in vitro rates of [U-14C]glucose incorporation into hepatic total lipids and into hepatic triacylglycerol were measured under basal, insulin (4 nM)-, gastric inhibitory polypeptide (GIP; 6 nM)- and insulin + GIP (4 nM + 6 nM)-stimulated conditions. Effects of the three diets on postprandial plasma triacylglycerol, cholesterol, insulin and GIP concentrations were also measured. The fish-oil diet decreased rates of basal glucose incorporation into hepatic total lipids (P < 0.05) and hepatic triacylglycerol, (P < 0.01) compared with the mixed-oil diet. The presence of insulin + GIP in the incubation medium stimulated glucose incorporation into hepatic total lipids in the maize-oil (P < 0.01) and fish-oil groups (P < 0.05), as well as into hepatic triacylglycerol in the maize-oil group (P < 0.005). In addition, the fish-oil diet decreased postprandial plasma triacylglycerol levels compared with both other dietary groups (P < 0.05 both cases), and the mixed-oil diet markedly increased postprandial plasma insulin levels compared with the other dietary groups (P < 0.001).     

The affinities of procolipase and colipase for interfaces are regulated by lipids

It has been suggested that at physiological pH, the trypsin-catalyzed activation of the lipase cofactor, procolipase, to colipase has no consequence for intestinal lipolysis and serves primarily to release the N-terminal pentapeptide, enterostatin, a satiety factor (Larsson, A., and C. Erlanson-Albertsson 1991. The effect of pancreatic procolipase and colipase on pancreatic lipase activation. Biochim. Biophys. Acta 1083:283-288). This hypothesis was tested by measuring the adsorption of [14C]colipase to monolayers of 1-stearoyl-2-oleoyl-sn-3-glycerophosphocholine and 13, 16-cis, cis-docosadienoic acid in the presence and absence of procolipase. With saturating [14C]colipase in the subphase, the surface excess of [14C]colipase is 29% higher than that of procolipase, indicating that colipase packs more tightly in the interface. With [14C]colipase-procolipase mixtures, the proteins compete equally for occupancy of the argon-buffer interface. However, if a monolayer of either or both lipids is present, [14C]colipase dominates the adsorption process, even if bile salt is present in the subphase. If [14C]colipase and procolipase are premixed for > 12 h at pH approximately 8, this dominance is partial. If they are not premixed, procolipase is essentially excluded from the interface, even if procolipase is added before [14C]colipase. These results suggest that the tryptic cleavage of the N-terminal pentapeptide of procolipase may be of physiological consequence in the intestine.     

Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole

BACKGROUND: The oral bioavailability of buspirone is very low as a result of extensive first-pass metabolism. Erythromycin and itraconazole are potent inhibitors of CYP3A4, and they increase plasma concentrations and effects of certain drugs, for example, oral midazolam and triazolam. The possible interactions of buspirone with erythromycin and itraconazole have not been studied before. METHODS: The pharmacokinetics and pharmacodynamics of buspirone were investigated in a randomized, double-blind, double-dummy crossover study with three phases. Eight young healthy volunteers took either 1.5 gm/day erythromycin, 200 mg/day itraconazole, or placebo orally for 4 days. On day 4, 10 mg buspirone was administered orally. Timed blood samples were collected up to 18 hours, and the effects of buspirone were measured with four psychomotor tests up to 8 hours. RESULTS: Erythromycin and itraconazole increased the mean area under the plasma concentration-time curve from time zero to infinity [AUC(0-infinity] of buspirone about sixfold (p < 0.05) and 19-fold (p < 0.01), respectively, compared with placebo. The mean peak plasma concentration (Cmax) of buspirone was increased about fivefold (p < 0.01) and 13-fold (p < 0.01) by erythromycin and itraconazole, respectively. These interactions were evident in each subject, although a striking interindividual variability in the extent of both interactions was observed. The elimination half-life of buspirone did not seem to be prolonged by either erythromycin or itraconazole. The effect of itraconazole on the Cmax and AUC(0-infinity) of buspirone was significantly (p < 0.01) greater than that of erythromycin. The greatly elevated plasma buspirone concentrations resulted in increased (p < 0.05) pharmacodynamic effects (as measured by the Digit Symbol Substitution test and the Critical Flicker Fusion test) and in side effects of buspirone. CONCLUSIONS: Both erythromycin and itraconazole greatly increased plasma buspirone concentrations, obviously by inhibiting its CYP3A4-mediated first-pass metabolism. These pharmacokinetic interactions were accompanied by impairment of psychomotor performance and side effects of buspirone. The dose of buspirone should be greatly reduced during concomitant treatment with erythromycin, itraconazole, or other potent inhibitors of CYP3A4.     

Dietary linoleic acid increases and palmitic acid decreases hepatic LDL receptor protein and mRNA abundance in young pigs

The present study was conducted to determine the effects of dietary fatty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich (30% of calories) in palmitic acid or linoleic acid. A control group was fed the base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary cholesterol increased (P < 0.05); however, there was no significant effect of either fatty acid. Dietary fatty acids, however, had distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01). The differential effects of fatty acids on LDLr expression were only observed at 0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant and repressive effect on regulation of LDLr expression. Cholesterol intake increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids had no effect on hepatic sterols. In summary, our results indicate that dietary linoleic acid and palmitic acid have markedly different effects on hepatic LDLr protein abundance that are mediated by differential effects on LDLr mRNA and protein levels. Further studies are needed to fully elucidate the molecular mechanisms by which fatty acids regulate LDLr mRNA and protein levels.     

Anxiety-related behaviors in the elevated zero-maze are affected by genetic factors and retinal degeneration.

Anxiety levels were tested in an elevated zero-maze for 8 inbred strains of mice that are used widely in biomedical and behavioral research. Strain differences were observed for activity, latency to enter an open quadrant, open time, and defecation, demonstrating that genetic factors mediate anxiety in this paradigm. Three of the strains have the rdl mutation that causes retinal degeneration and were less anxious in the maze. To discern whether visual acuity is a source of difference on the maze, anxiety levels were tested in a congenic strain in which the rdl allele has been replaced with the wild-type allele. The congenic strain, with normal vision, had higher levels of anxiety. This study provides baseline data for the selection and use of any of these strains in pharmacological challenges in the maze, and provides a starting point of the identification of strains that may have appropriate backgrounds for targeted mutation studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Word priming and recognition memory are both affected by mesial temporal lobe damage.

Amnesic patients with mesial temporal lobe pathology often produce normal priming effects despite severely impaired memory. This is generally interpreted to mean that whereas limbic structures are involved in conscious memory, other structures, comprising a separate memory system, mediate priming effects. Priming and recognition memory measures were correlated with magnetic resonance imaging (MRI) measures of damage to specific brain structures in a sample of 30 Ss. The results provide evidence that both priming and recognition memory may be adversely affected by mesial temporal lobe damage. Furthermore, the results suggest that striatal damage is associated with lexical or perceptual deficits and larger measured priming effects. Thus, co-existing striatal and limbic damage may lead to normal priming performance in some memory-impaired patients. In these instances, normal priming performance may not be mediated by a separate (implicit) memory processing system in the brain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The composition of dietary lipids and the blood coagulation time in the rat

The study of the coagulation in rats fed with a balanced diet, including 12% of different animal or vegetable fats, during 6 months, shows that the time of coagulation in rats receiving one of the following oils: palm, sunflower, Canbra, is significantly higher than the ones fed with butter. On the other hand, the coagulation time observed in the groups is correlated with the oleic acid level in the corresponding diet. The results obtained here may lead to important practical applications.     

Pretreatment with intraventricular aurintricarboxylic acid decreases infarct size by inhibiting apoptosis following transient global ischemia in gerbils

The goal of this study was to determine whether aurintricarboxylic acid (ATA), an endonuclease inhibitor known to inhibit apoptosis, could ameliorate cell damage in a gerbil model of transient ischemia. Transient ischemia was induced in gerbils by bilateral carotid artery occlusion for a period of 5 minutes. Four micrograms of ATA was administered intraventricularly 1 hour before ischemia, and the brains were assessed histologically 1 week later to quantitate cell loss in the vulnerable CA-1 subsector of the hippocampus. In a separate set of experiments, 4 microg of ATA was administered intraventricularly 1 hour before ischemia and the brains were assessed for evidence of DNA fragmentation by the TUNEL method. There was only a 16% cell loss compared with nonischemic controls in animals pretreated with ATA that was significantly less (p < 0.05) than the 48% cell loss in animals pretreated with saline alone. TUNEL-positive cells were first evident at 3 days and were still present at 7 days subsequent to ischemia. Maximal staining occurred at 4 days. Pretreatment with ATA virtually eliminated TUNEL staining at 4 days. These results support the hypothesis that the delayed cell death secondary to transient ischemia is, in part, apoptotic. Furthermore, ATA afforded significant neuronal protection and prevented DNA fragmentation.     

Modification of red cell membrane lipids by hypochlorous acid and haemolysis by preformed lipid chlorohydrins

Hypochlorous acid (HOCl), a strong oxidant generated by the myeloperoxidase system of neutrophils and monocytes, has been implicated in inflammatory tissue damage by these cells. Reaction of HOCl with the double bonds of unsaturated lipids produces alpha, beta-chlorohydrin isomers. We have exposed red cell membranes to HOCl and used thin layer chromatography (TLC) of the extracted lipids and enzyme-linked immunosorbent assay (ELISA), using an antichlorohydrin monoclonal antibody, to show that fatty acyl chlorohydrins are formed. The ELISA was approximately 25 fold more sensitive than TLC, and chlorohydrins were detected when membranes from 10(6) cells were treated with > or = 0.16 nmoles HOCl. Lipid chlorohydrins are more polar and bulky than their parent lipids and as such could affect membrane stability and function. To determine the effect of incorporation of lipid chlorohydrins into cell membranes, preformed fatty acid and cholesterol chlorohydrins were incubated with red cells. Lysis was measured as release of haemoglobin and incorporation of lipids was determined by 14C scintillation counting. Addition of HOCl-treated oleic acid to red cells resulted in rapid lysis of a fraction of the cells in a concentration dependent manner. HOCl-treated cholesterol also caused a small amount of cell lysis that was predominantly due to chlorohydrin 3, one of the three major cholesterol chlorohydrin products. Chlorohydrin 3, which has a decreased planarity and polarity, was also primarily responsible for altering the critical micelle concentration of HOCl-treated cholesterol-containing liposomes.     

Visual attention in infant monkeys: Effects of dietary fatty acids and age.

Effects of dietary essential fatty acids on visual attention were explored longitudinally in infant rhesus monkeys with a visual paired-comparison paradigm. Sets of primate faces and of patterns were presented at Weeks 2, 5, 9, and 13 to 9 infants deficient in ω-3 fatty acids and 8 fed a standard nursery diet. Familiarization to 1 member of each pair preceded simultaneous presentation of both stimuli. Infants fed the deficient diet showed longer individual looks in both immediate and 24-hr tests. Duration of looks decreased with age to familiar but not to novel stimuli. The proportion of time looking at the novel stimulus (% novel) increased with age but was not affected by diet. Look duration and % novel were differentially affected and may reflect different underlying processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physiological and induced neuronal death are not affected in NSE-bax transgenic mice

The intracortical organization of the noradrenaline (NA) and vasoactive intestinal polypeptide (VIP) systems provides ample opportunity for functional convergence, and accumulated evidence indicates that NA and VIP share certain cellular actions upon both neuronal and nonneuronal cortical elements. In the present study, a double immunolabeling method was combined with a silver-gold intensification procedure to examine the ultrastructural relationships of the NA coeruleocortical afferents and the intrinsic VIP neurons with three main constituents of the cortex: neurons, astrocytes, and blood vessels. Electron microscopy of singly or doubly labeled material indicated that NA and VIP boutons are engaged in a variety of anatomical relationships with both neuronal and nonneuronal elements. Dendritic shafts and perikarya of nonpyramidal neurons, some of which are VIP positive, receive combined NA and VIP synapses. A significant number of cortical microvessels are in intimate contact with NA or VIP profiles. NA axons often form perivascular loops, and VIP dendritic shafts of large diameter are frequently observed to bend around the vessel circumference. Serial section examination demonstrates that some NA boutons are directly apposed to the capillary wall at sites of glial end-feet discontinuities, whereas VIP boutons contact astrocytic sleeves of capillaries but never cross the perivascular astroglial barrier. Some VIP dendrites containing coated vesicles make intimate contact with the capillary basal lamina. Astrocytic perikarya, mainly in the supragranular layers, are also directly apposed to NA and/or VIP elements. These complex anatomical relationships provide a structural basis for the known interactions between NA and VIP in the control of cortical metabolism and function.