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[Studies of cardiac metabolism with 123I-labelled fatty acids and 11C-methylglucose (author's transl)].

To characterize externally detectable changes in the myocardial metabolism of free fatty acids (FFA) and glucose, which are associated with ischemia and cardiomyopathy, omega-123I-heptadecanoic acid (stearic acid analogue), 75Br-phenylpentadecanoic acid, and 3-0-11C-methyl-D-glucose were used as indicators. It could be demonstrated that in the metabolism of free fatty acids at least two different patho-physiological situations may exist. Disturbances in the mechanism of the accumulation of free fatty acids lead to a decrease of the amount of the free fatty acids which are available for energy production (these disturbances can be recognized as indicator accumulation defects). Disturbances associated with the mechanism of free fatty acid catabolism lead to a decrease of the ability of the myocardial cell to utilize the free fatty acids (these disturbances can be recognized as changes in indicator elimination rates). Whereas in ischaemic heart disease, the areas with altered FFA accumulation correlate with the areas of altered FFA-elimination, no correlation was found in the case of cardiomyopathy. The 11C-methylglucose seems to be an excellent indicator for the in-vivo assessment of the function of transport system in the myocardial cell membrane.

Animals↗

[Lipoproteins and fatty acids--hyperlipoproteinemia and arteriosclerosis].

At first on the basis of literature a short description of the interrelations between lipoprotein metabolism and fatty acid metabolism as well as hyperlipoproteinaemia on the one hand and arteriosclerotic-degenerative diseases of the coronary vessels on the other is given. Finally, the findings of gas-chromatographic analyses of the patterns of fatty acids of the cholesterol ester and triglyceride fractions of the serum of 252 patients with primary hyperlipoproteinaemia are represented. In contrast to persons with healthy metabolism increase of the proportions per cent of palmitic acid, stearic acid, palmitoleic acid, oleic acid, and eikosatrienic acid was shown and decrease of those ones of linoleic acid, linolenic acid, arachidonic acid, and eikosapentaic acid in the cholesterol ester fractions in hyperlipoproteinaemia type IIa and IIb and in the triglyceride fractions in hyperlipoproteinaemia type IIb and IV. The shifts within the patterns of fatty acids in hyperlipoproteinaemia are an expression of an atherogenic risk. Disturbances of the hepatogenic synthesis of fatty acids and oxydation of fatty acids, increased reesterification from the depot fat of mobilised fatty acids as well as a partially increased LCAT-activity are causally discussed.

Arteriosclerosis↗

[Lipid-reducing basic diet and serum fatty acid levels].

In 50 patients with primary hyperlipoproteinaemia during a 3 year treatment with lipid reducing metabolic basis diet in intervals of 4 months the composition of the cholesterol ester and triglyceride fatty acids of the serum was determined by means of gas chromatography. After 12--16 months in the hyperlipoproteinaemia type IIa (10 patients) in the cholesterol ester fraction, after 12 months in the hyperlipoproteinaemia type IIb (10 patients) in the cholesterol ester fraction and in the triglyceride fraction significant changes of the spectre of fatty acids developed. Palmitic acid, stearic acid, palmitoleic acid, oleic acid and eikosatrienic acid decreased, and linolic acid, linolenic acid, arachidonic acid and eikosapentaenic acid increased. In the course of the further therapy the precental proportions of the fatty acids did no more change. Triglyceride fatty acids in hyperlipoproteinaemia of type IIa and cholesterol ester fatty acids in hyperlipoproteinaemia of type IIb were not influenced. These metabolic effects of the metabolic basis diet on the spectres of fatty acids of cholesterol ester and triglyceride fractions in primary hyperlipoproteinaemia of type IIa, IIb and IV must not be seen only in their increased content of polyene fatty acids which influences the hepatogenic processes of synthesis and oxydation of fatty acids, but are traced back also to the reduced proportions of fat, mono- and disaccharide. With metabolic basis diet decreasing lipids alone we, however, did not succeed in normalising fully the composition of fatty acids, and the constellations of fatty acids of test persons with healthy metabolism were reached only approximately.

Cholesterol↗

[Arachidonic acid in the liver, ovary and uterus of cows with various reproductive capability].

Research was carried out at two localities ecologically different, i.e. in the "relatively" clean region of Klatovy, designed according to the standards of the Czech Ministry of Environment as a region with above-average quality environment and in the considerably affected region of Prague-East, designed as a region with below-average quality environment. The first group included 33 cows from herds with good fertility (average conception rate after 1st insemination 61.5 and service period 88 days) and the dairy cows were eliminated for reasons different as reproductive disorders (Klatovy), in the second group all 18 cows were eliminated because of reproductive disorders (Prague-East) and they were from the herds with much lower fertility (average conception rate after 1st insemination 46.9% and service period 107 days). Samples of liver, uterus and ovarian tissues of the cows were processed according to the method after Jarý et al. (1987), analysed on the gas chromatograph Varian--Aerogramm 2100. The data obtained were processed on a computer IBM PC--AT with a numeric co-processor, and the programme Quatro Pro, version 2.0 was used. Differences in average amounts measured in both regions are objectively characterized in Figs. 1, 2 (with marked scatterings) and correspond to the amount given in Tab. I. As regards the saturated acid, stearic acid and oleic acid, no remarkable differences were found according to the localities (Klatovy and Prague), with the exception of the average contents of those acids in uterine horns. In that case the region of Klatovy is dominating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of controlled-release mosquito repellent formulations.

Eight polymer and 9 microcapsule formulations of deet were tested on laboratory rabbits against Aedes aegypti and Anopheles albimanus. Several formulations were significantly more effective than simple (unformulated) deet at the same strength for periods up to 24 h. Best results were obtained with a polymer formulation containing a high molecular weight fatty acid and 3 microcapsule formulations containing lanolin, gum arabic, gelatin, tannic acid, stearic acid, polypropylene glycol, water, and a commercial lotion in the microcapsule and carrier fractions.

Aedes↗

[Factors aggravating bronchial asthma in urban children (II)--The involvement of atopy and serum fatty acids, and their interaction with urban living environment].

The aggravation of bronchial asthma in today's urban child population was studied by an epidemiological study in order to elucidate the involvement of food habits as well as individual factors such as age, sex, and history of atopic dermatitis, and the interaction with urban living environments. The asthma group consisted of 202 children under 12 years old who had been recently diagnosed as having bronchial asthma and under the care of Osaka Prefectural Habikino Hospital. The non-asthma group consisted of 81 children under 12 years old who had been under care at Osaka Prefectural Hospital but had no present history of allergic symptom. The individual factors and the urban living environments (atmospheric environment, housing style) were surveyed by questionnaire. Also, the mite (Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae) specific immunoglobulin E (Dp-IgE, Df-IgE) and the composition of serum fatty acid were examined as objective indicators for atopy and dietary habits, respectively. In this study, bronchial asthma was classified into two types: atopic/non-atopic, according to whether Dp-IgE was present/absent (positive/negative). Thus, for the risk factors given above, their involvement in each type of asthma was examined. As atopy is an important factor of child asthma, the relative risk (odds ratio) of Dp-IgE increase (atopy) was also examined by logistic regression analysis in each of the asthma and non-asthma groups. The results are as follows: 1. As age increased, the risk of atopy increased but the risk of asthma decreased. 2. The risk of asthma increased as Dp-IgE rather than Df-IgE increased. 3. For the composition of serum fatty acid, the lower quartile ranking (LQR) group for a saturated fatty acid, stearic acid, and the upper quartile ranking (UQR) group for a mono-unsaturated fatty acid, oleic acid, had a higher risk of nonatopic asthma. 4. The LQR group for omega 6-poly-unsaturated fatty acid such as linoleic acid, had a lower risk of atopy. 5. The UQR group for a omega 3-poly-unsaturated fatty acid, eicosapentaenoic acid, had a higher risk of nonatopic asthma. The UQR of eicosapentaenoic acid and living environments within 25 m from a major road or housing of reinforced concrete structure showed involvement in synergistic increase in the risk of non-atopic asthma.

Asthma↗

Gastroretentive drug delivery system of ranitidine hydrochloride: formulation and in vitro evaluation.

The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 3(2) full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2 = 75) among all the batches, and this similarity is also reflected in t50 (approximately 214 minutes) and t80 (approximately 537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile.

Chemistry, Pharmaceutical↗

Uptake and oxidation of elaidic acid by Ehrlich ascites tumor cells.

The present studies were designed to investigate some aspects of trans fatty acid metabolism by Ehrlich ascites tumor cells, i.e., uptake, oxidation and incorporation into cellular lipids. Elaidic acid (18:1delta9, trans) was compared with its cis counterpart (oleic acid) and with stearic acid (18:0) in its metabolism. These studies indicate that tumor cells take up elaidic acid at the same rate as stearic acids. Stearic acid is taken up at a higher rate than oleic acid. The oxidation of these fatty acids to CO2 by tumor cells followed the same pattern of uptake, i.e., elaidic acid was oxidized at the same rate as stearic acid but at a higher rate than oleic acid. In that tumor cells are different from the normal cells that are known to oxidize trans fatty acids at a slower rate as compared with their cis counterparts. The incorporation of these fatty acids into tumor cell lipids was found to be different. These data indicate that tumor cells handle elaidic acid differently than normal cells in some aspects of its metabolism.

Animals↗

Spin-label studies on the origin of the specificity of lipid-protein interactions in Na+,K+-ATPase membranes from Squalus acanthias.

The pH dependence and salt dependence of the lipid-protein interactions of phosphatidic acid, phosphatidylserine, and stearic acid with Na+,K+-ATPase membranes from Squalus acanthias have been studied with spin-label electron spin resonance spectroscopy, using lipids with nitroxide labels on the 14-position C atom of the sn-2 chain. For phosphatidic acid and stearic acid, the fraction of motionally restricted spin-label increases with increasing pH, with pKa's of 6.6 and 8.0, respectively. In contrast, the pKa of stearic acid in the bulk lipid environment of the membrane is estimated from spin-label spectroscopy to be approximately equal to 6.6. The fraction of motionally restricted phosphatidylserine spin-label remains constant over the pH range 4.7-9.2. In the fully dissociated state the fractions of motionally restricted spin-labeled phosphatidic and stearic acids decrease with increasing salt concentration, reaching an approximately constant value at [NaCl] = 0.5-1.0 M. For stearic acid the net decrease is comparable to that obtained on protonation, but for phosphatidic acid the decrease is considerably smaller (by approximately 55%) than that obtained on protonating the lipid. The fraction of motionally restricted phosphatidylserine spin-label varies relatively little with salt concentration up to 1 M NaCl. Direct electrostatic effects alone cannot account for the whole of the observed specificity of interaction of the two phospholipids with Na+,K+-ATPase membranes.

Animals↗

Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study.

BACKGROUND: The effect of individual dietary fatty acids on emerging risk factors for cardiovascular disease that are associated with subclinical inflammation is unknown. OBJECTIVE: The goal was to evaluate the role of dietary fat and specific fatty acids, especially trans fatty acids, in altering concentrations of markers of inflammation in humans fed controlled diets. DESIGN: In a randomized crossover design, 50 men consumed controlled diets for 5 wk that provided 15% of energy from protein, 39% of energy from fat, and 46% of energy from carbohydrate. Eight percent of fat or fatty acids was replaced across diets with the following: cholesterol, oleic acid, trans fatty acids (TFAs), stearic acid (STE), TFA+STE (4% of energy each), and 12:0-16:0 saturated fatty acids (LMP). RESULTS: Fibrinogen concentrations were higher after consumption of the diet enriched in stearic acid than after consumption of the carbohydrate diet. C-reactive protein concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet, but were not significantly different after consumption of the TFA and TFA+STE diets than after consumption of the LMP diet. Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP, TFA, and STE diets. E-selectin concentrations were higher after consumption of the TFA diet than after consumption of the carbohydrate diet. Consumption of the TFA but not the TFA+STE diet resulted in higher E-selectin concentrations than did the LMP diet. CONCLUSIONS: These data provide evidence that dietary fatty acids can modulate markers of inflammation. Although stearic acid minimally affects LDL cholesterol, it does appear to increase fibrinogen concentrations.

Adult↗

Streptozotocin increases free fatty acids and decreases phospholipids in rat brain.

Streptozotocin (STZ) is a diabetogenic drug that disrupts glucose and energy metabolism in brain. To study its effect on brain lipids, tissue concentrations of free fatty acids and phospholipids were measured in the temporal cortex and the hippocampus of adult rats 3 weeks after a single intracerebroventricular (icv) injection of STZ. STZ increased concentrations of palmitic acid and stearic acid in temporal cortex and these of arachidonic acid both in the anterior part of the hippocampus and in CA1. In addition, palmitic acid and stearic acid concentrations were elevated in the anterior hippocampus. In contrast, STZ decreased brain cortex levels of phosphatidylethanolamine and phosphatidylserine. These data show that STZ alters brain lipid metabolism. They suggest that oxidative phospholipid breakdown is accelerated by STZ. These changes may be related to decreased brain glucose utilization and energy formation.

Animals↗

In vitro incorporation of isomeric cis-octadecenoic acids by rat liver mitochondria.

The metabolic fate of positional isomers of cis-octadecenoic acids was compared to that of oleic acid, elaidic acid and stearic acid in rat liver mitochondria. The positional isomers as well as elaidic acid and stearic acid were labelled with 3H and they were incubated in pairs with [1-14C]oleic acid. 3H/14C ratios were determined for the administered mixtures and for the isolated lipid classes. The results suggested that all isomers were readily incorporated into the membraneous structure of mitochondria. Those with the double bond in the middle of the acyl chain resembled oleic acid and they were preferentially incorporated in cholesterol esters, triacylglycerols and in the 2-position of triacylglycerols and of phosphatidylcholines. Those with the double bond away from the middle of the chain were metabolically distinct from oleic acid and behaved like trans fatty acids. They were rapidly taken up by mitochondria. They were preferentially incorporated in phospholipids and they occupied the 1-position in phosphatidylcholines and the 1- and 3-positions in triacylglycerols.

Animals↗

Triacylglycerol biosynthesis in rat adipose-tissue homogenates.

The optimum cofactor requirements for triacylglycerol biosynthesis in rat adipose-tissue homogenates containing mitochondrial, microsomal and cytosolic fractions were investigated. In general the optimum concentrations of cofactors for triacylglycerol biosynthesis were found to differ from those for total fatty acid esterification. The results provided further evidence for the key role of phosphatidate phosphohydrolase in the regulation of triacylglycerol biosynthesis. Albumin was included in the incubation medium to permit the use of concentrations of added fatty acids that would swamp the effects of endogenous fatty acids. The addition of albumin had little effect on the incorporation of palmitic acid and stearic acid into lipids including triacylglycerols. By contrast, a critical concentration of albumin (about 60 muM) was required before incorporation of oleic acid or linoleic acid into triacylglycerols occurred. The system was used to study the incorporation of different 1-14C-labelled fatty acids from a mixture of unesterified fatty acids [palmitic acid 30%; stearic acid 10%; oleic acid 40%; linoleic acid 20% (molar percentages)] separately into the positions 1,2 and 3 of triacyl-sn-glycerols. In general the stereo-specific distribution of the labelled fatty acids incorporated into triacylglycerols paralleled the normal distribution of fatty acids within rat adipose-tissue triacylglycerols, suggesting that the specificities of the relevant acyltrasferases have the major role in determining the positional distribution of fatty acids within triacylglycerols.

Adipose Tissue↗

Studies on the cellular location, physical properties and endogenously attached lipids of acylated proteins in human squamous-carcinoma cell lines.

The location of cell proteins with covalently attached lipid was examined in two human squamous-carcinoma cell lines. Cells were labelled with either palmitic acid or myristic acid and disrupted by sonication, followed by differential centrifugation of the cell lysates. SDS/polyacrylamide-gel electrophoresis of the resulting cell fractions indicated that most of the palmitate-labelled proteins were found in cell membranes, whereas most of the myristate-labelled proteins were found in the cytosol, although some were located in cell membranes. Experiments with lipid-labelled proteins extracted with the phase-separable detergent Triton X-114 showed that palmitate-labelled proteins behaved as hydrophobic proteins, partitioning into the lower phase of the detergent, whereas most of the myristate-labelled proteins remained in the upper phase. Although one of these cell lines expressed large amounts of epidermal-growth-factor receptor, this could not be labelled by either myristic acid or palmitic acid, whereas transferrin receptor was labelled by palmitic acid. The lipids normally attached to cell proteins in these two human squamous-carcinoma cell lines were characterized by labelling the cells with [3H]acetate. The labelled cell proteins were exhaustively extracted with organic solvents, and subjected to sequential alkaline and acid hydrolyses to release the attached lipids, which were then analysed by h.p.l.c. Most of the lipid released by the alkaline treatment chromatographed as palmitic acid or stearic acid, whereas the subsequent acid treatment released myristic acid as well as some palmitic acid and stearic acid. No other fatty acids apart from these were found attached to cell proteins.

Acetates↗

Fatty acid binding protein in kidney of normotensive and genetically hypertensive rats.

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats (SHRSP). Wistar-Kyoto rats (WKY) were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive SHRSP than in control WKY (0.155 +/- 0.006 vs 0.030 +/- 0.001 mol palmitic acid/mol protein). However, in 40-week-old rats, the activity was decreased only in SHRSP with established hypertension (0.035 +/- 0.002 vs 0.028 +/- 0.003 mol palmitic acid/mol protein WKY). Fatty acid compositions were similar among 5-week-old and 40-week-old control WKY and 5-week-old SHRSP (palmitic acid, 24%; stearic acid, 14%; oleic acid, 30%; linoleic acid, 29%; arachidonic acid, 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old SHRSP, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old SHRSP had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid, 8%; stearic acid, 2%; oleic acid, 4%; linoleic acid, 10%; arachidonic acid, 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.

Animals↗

[Studies on the function of fatty acid binding protein in hypertensive rat kidney].

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats. Wistar-Kyoto rats were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive spontaneously hypertensive stroke-prone rats (0.155 +/- 0.006 mol palmitic acid/mol protein) as compared with control values in Wistar-Kyoto rats (0.030 +/- 0.001). However, in 40-week-old rats, the activity was decreased only in spontaneously hypertensive stroke-prone rats with established hypertension (0.035 +/- 0.002), and it did not decrease in Wistar-Kyoto rats (0.028 +/- 0.003). Fatty acid compositions were similar among 5 and 40-week-old control rats and 5-week-old hypertensive rats (palmitic acid 24%, stearic acid 14%, oleic acid 30%, linoleic acid 29%, arachidonic acid 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old hypertensive rats, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old hypertensive rats had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid 8%, stearic acid 2%, oleic acid 4%, linoleic acid 10%, arachidonic acid 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.

Animals↗

[Chemical and nutritional characterization of amaranthus (Amaranthus cruentus)].

Two samples of Amaranthus cruentus harvested in 1987 (sample A) and 1990 (sample B) were studied. Whole and refined flours were obtained. The whole flours contained 14.6 and 12.6% protein and 6.6 and 7.3 ether extraction, respectively. Both samples contained significant levels of Ca, P, Mg and K. Amaranth oil contained 19% palmitic acid, 3.4% stearic acid, 3.4% stearic acid, 34% oleic acid and 33% linoleic acid. Docosaenoic acid (C22:1) was present at the level of 9%. The ratio of saturated to unsaturated fatty acids was approximately 1:3. The level of crude fiber was 3.7% in the whole flours and 2.4% in the refined ones. Biological protein quality of flours was measured in the rat by the net protein ratio (NPR) method. The NPR values of the four materials tested ranged from 3.04 to 3.20 (NS), as compared with 4.08 for casein. These values are equivalent to 75-78% of the standard protein. Blends of raw wheat flour and whole amaranth flour fed to rats produced a good complementary effect between proteins, as shown by PER test. Wheat flour gave a poor PER value of 0.54. However, this figure increased with every increment of amaranth flour reaching a value of 2.15 for the blend 25:75. The PER for the amaranth diet (0:100) was 1.94 (casein 2.77). As expected, the extrusion process applied to the wheat/amaranth and corn/amaranth mixtures improved the biological quality of the protein. The wheat flour diet (100:0) gave a PER value of 1.64. Mixture 90:10 produced a low non significant increase in the protein quality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗