Fasting increases tissue uptake and interconversion of plasma unesterified linoleic acid in guinea pigs

A large part of the arachidonic acid (20:4 n-6) pools in some extrahepatic tissues can be formed by local interconversion of linoleic acid (18:2 n-6) taken up as free fatty acid (FFA) from blood in both rats and guinea pigs. This study investigates the rate of uptake and interconversion of unesterified 14C-18:2 by different tissues in fasted guinea pigs. The initial half-life of 14C-18:2 in plasma was 5.8 s. The average concentration of plasma FFA was 551.3 nmol ml-1 and of plasma FFA-18:2 was 67.3 nmol ml-1. The total amount of 20:4 formed in the liver was 1.8 +/- 0.3 nmol min-1, which was lower than that in the gastrointestinal tract (3.1 nmol min-1), bone marrow (6.0 nmol min-1) and lung (2.1 nmol min-1). Due to the fast turnover and higher concentration of plasma FFA-18:2 in the fasting state, the retained 18:2 in tissue lipids was 5.8-25.6-fold higher than that in fed guinea pigs [L. Zhou et al. Biochim. Biophys. Acta 1349 (1997) 197-210]. The total delta 6-desaturase products both in liver and in extrahepatic tissues were also increased, 3.8-fold in liver, 7.2-fold in upper small intestine, 6.0-fold in colon, and 6.5-fold in bone marrow. The increased rate of tissue uptake of FFA during fasting is thus linked to an increased local interconversion of plasma FFA-18:2, which is an important source of 20:4 in some extrahepatic tissue in guinea pigs.     

Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats

Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.     

Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters

Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.     

Tissue uptake and interconversion of plasma unesterified 14C linoleic acid in the guinea pig

The prevalence of different etiologic factors has been evaluated in 350 male patients consulting the same physician in an urban, ambulatory setting for primary or secondary infertility of more than 1 year. Environmental factors such as alcohol or drugs represented 12% of the etiologies, acquired diseases such as varicocele and prostatitis 40%, congenital diseases and primary testicular failure 16.2%, idiopathic cases 19.4%, and abnormality of sperm transport 7.4%. The severity of sperm alterations in the different etiologic categories was evaluated by the total motile sperm count per ejaculate (TMS) (normal > 16). The TMS was less than 5 in classical causes of male infertility such as testicular failure, endocrinopathy, cancer, or antisperm antibodies. It was more than 10 in controversial causes of infertility such as varicocele, prostatis, chlamydial infections, and professional exposure to heat. After treatment, there was a nonsignificant increase of the TMS in the latter cases. In cases of azoospermia of pituitary origin, the TMS was normalized by a hormonal treatment. In some cases of azoospermia of possible obstructive origin, sperm appeared in the ejaculate after diclofenac treatment. The utility of andrological investigation and treatment is discussed.     

Dietary linoleic acid intake controls the arterial blood plasma concentration and the rates of growth and linoleic acid uptake and metabolism in hepatoma 7288CTC in Buffalo rats

In this study, we tested the hypothesis that dietary linoleic acid intake controls the arterial blood plasma linoleic acid concentration and the rates of tumor growth and linoleic acid metabolism in vivo. Seven groups of young male Buffalo rats (11-21 rats/group) were given free access to semipurified diets containing different amounts of corn and/or olive oils. Four other groups (7-11 rats/group) were 30% energy-restricted. Each experiment included periods for rat growth and plasma lipid stabilization (6 wk), measurement of mean daily arterial blood plasma fatty acid concentrations (3 wk), surgical implantation of a subcutaneous tissue-isolated hepatoma 7288CTC, tumor growth and harvest (2-4 wk). Linoleic + arachidonic acid (P = 0.007) and oleic acid (P = 0.002) concentrations in arterial blood plasma were increased as dietary intake of linoleic and oleic acids was increased, respectively. In rats given free access to food, tumor growth was directly dependent on the plasma concentrations of linoleic (P < 0.001) and arachidonic acids (P = 0.04). Tumor growth in energy-restricted rats was dependent only on the linoleic acid concentration (P = 0.008). Energy restriction itself caused a growth inhibition independent of plasma linoleic acid. The linoleic acid and total fatty acid concentrations of tumor triacylglycerols were directly dependent on the plasma linoleic acid concentration in rats given free access to food (P = 0.009). Hepatoma 7288CTC (both in vivo and during perfusion in situ) supported a dose-dependent conversion (P < 0.001) of plasma linoleic acid to the mitogen, 13-hydroxy-9, 11-octadecadienoic acid. We conclude that increased arterial blood plasma linoleic acid concentrations, caused by increased dietary intakes, specifically stimulate growth, lipid storage and linoleic acid metabolism in hepatoma 7288CTC in vivo.     

Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis

The effect of dietary alpha-linolenic acid (18:3n-3) and its ratio to linoleic acid (18:2n-6) on platelet and plasma phospholipid (PL) fatty acid patterns and prostanoid production were studied in normolipidemic men. The study consisted of two 42-d phases. Each was divided into a 6-d pre-experimental period, during which a mixed fat diet was fed, and two-18 d experimental periods, during which a mixture of sunflower and olive oil [low 18:3n-3 content, high 18:2/18:3 ratio (LO-HI diet)], soybean oil (intermediate 18:3n-3 content, intermediate 18:2/18:3 ratio), canola oil (intermediate 18:3n-3 content, low 18:2/18:3 ratio) and a mixture of sunflower, olive and flax oil [high 18:3n-3 content, low 18:2/18:3 ratio (HI-LO diet)] provided 77% of the fat (26% of the energy) in the diet. The 18:3n-3 content and the 18:2/18:3 ratio of the experimental diets were: 0.8%, 27.4; 6.5%, 6.9; 6.6%, 3.0; and 13.4%, 2.7, respectively. There were appreciable differences in the fatty acid composition of platelet and plasma PLs. Nevertheless, 18:1n-9, 18:2n-6 and 18:3n-3 levels in PL reflected the fatty acid composition of the diets, although very little 18:3n-3 was incorporated into PL. Both the level of 18:3n-3 in the diet and the 18:2/18:3 ratio were important in influencing the levels of longer chain n-3 fatty acid, especially 20:5n-3, in platelet and plasma PL. Production of 6-keto-PGF1 alpha was significantly (P < 0.05) higher following the HI-LO diet than the LO-HI diet although dietary fat source had no effect on bleeding time or thromboxane B2 production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of conjugated linoleic acid on body composition in mice

Cube resin, used as an insecticide/miticide and piscicide, contains in decreasing amounts rotenone (1), deguelin (2), the 6a,12a-dehydro derivatives of rotenone (3) and deguelin (4), and the newly-discovered 13-homo-13-oxa-6a,12a-dehydro analogs [referred to as oxadehydrorotenone (5) and -deguelin (6)]. These six rotenoids were compared for potency as inhibitors of NADH:ubiquinone oxidoreductase activity and for organismal toxicity to mosquito larvae, goldfish, and mice and cytotoxicity in three mammalian cell lines (Hepa 1C1C7, MCF 7, and NB 41A3). Although rotenoids 3-6 contribute very little to the overall activity of cube resin, there were two surprising aspects to the structure-activity relationships. First, 1 was 7-15-fold more active than 2 in the cytotoxicity assays of 4-day duration but not in the other systems. This difference in cytotoxicity is not due to specificity at the oxidoreductase target but instead to more extensive cytochrome P450-dependent (piperonyl butoxide-sensitive) detoxification of 2 than of 1. Second, the observed potency increase on conversion of dehydrorotenone to either rotenone or oxadehydrorotenone suggests that combining both structural changes to form cis-13-homo-13-oxarotenone (8) might result in maximal activity. Accordingly, 5 was reduced with diisobutylaluminum hydride to the trans-isomer 7 and then epimerized with aqueous pyridine to the cis-isomer 8 of the same configuration as 1. Surprisingly, 8 was much less active than 1. This is rationalized on the basis of conformational changes in the B/C ring system and decreasing dihedral angle (determined by X-ray crystallography and/or molecular modeling) between the A and D rings that follow the potency order, i.e., rotenoids 1 and 2 > oxadehydrorotenoids 5 and 6 > trans- and cis-oxarotenoids 7 and 8 > dehydrorotenoids 3 and 4. Thus, the novel oxarotenoids and oxadehydrorotenoids help define the conformation optimal for NADH:ubiquinone oxidoreductase inhibition and toxicity.     

Inhibition in vitro linoleic acid peroxidation and haemolysis by caffeoyltryptophan

Antioxidant activities of caffeoyltryptophan were investigated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging system, the superoxide anion generation system and the superoxide anion-mediated linoleic acid peroxidation system. At 10 microM, caffeoyltryptophan showed greater scavenging activity on DPPH than dl-alpha-tocopherol or ascorbic acid. DPPH radical scavenging activity of caffeoyltryptophan increased dose-dependently at concentrations ranging from 1 to 50 microM; 1 mol of caffeoyltryptophan reacted with ca 4 mol of radical. Caffeoyltryptophan caused 80% inhibition of superoxide anion generation at 50 microM. The inhibitory activity of caffeoyltryptophan was as strong as that of 5-caffeoylquinic acid. Caffeoyltryptophan inhibited the formation of conjugated diene from linoleic acid. The inhibitory activity increased in the order caffeic acid < 5-caffeoylquinic acid < caffeoyltryptophan < dl-alpha-tocopherol. Effects on the in vitro haemolysis and peroxidation of mouse erythrocytes induced by H2O2 were also examined. Caffeoyltryptophan exhibited strong inhibitory activities; Tryptophan was ineffective in these systems. These data suggest that caffeoyltryptophan may be a natural antioxidant in the human diet and, as such, may intervene in toxicological processes that are mediated by radical mechanisms.     

A note on distribution of human plasma levels of ascorbic and dehydroascorbic acid

Ascorbic acid concentrations in 102 human plasma samples ranged from 1 to 15 micrograms ml-1 with a mean concentration at about 8 micrograms ml-1, corresponding to the results of other authors. Dehydroascorbic acid was found only in traces, independent of ascorbic acid concentrations. The ascorbic acid concentrations in plasma of four persons, examined twice with a four-years interim period revealed no obvious differences over time. It is suggested that the variability of plasma ascorbic acid concentrations is mainly determined by long-term dietary habits.     

Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in murine keratinocytes

Using a T-maze, the influence of transient global cerebral ischemia on working memory in gerbils was investigated. Furthermore, it was examined whether a correlation exists between impairment in choice accuracy in the T-maze and neuron loss in the hippocampus. In two experiments, male Mongolian gerbils were tested in a previously learned delayed alternation T-maze task 1 week after a 4 min occlusion of the common carotid arteries. In both experiments memory was significantly impaired and in the second experiment, where the design allowed a separation between working and reference memory deficits, a selective impairment in working memory was seen. The results suggest that ischemia-induced disruption of delayed alternation in the T-maze in gerbils is a model which is relevant to the clinical manifestations of vascular dementia.     

Replacement of linoleic acid with alpha-linolenic acid does not alter blood lipids in normolipidaemic men

A retrospective immunohistochemical study of 33 cases of primary thyroid carcinomas and 5 cases of metastases to thyroid was carried out. The immunostaining for thyroglobulin and calcitonin was done by peroxidase-anti-peroxidase (PAP) technique. The optimum staining results were obtained by proper standardisation of the staining procedure and reagents. The sections were systematically evaluated for immunostaining intensity and distribution. The observations revealed that thyroglobulin and calcitonin could be useful as sensitive and specific histogenetic markers for follicular and parafollicular cell derived thyroid carcinomas respectively. However, there was no absolute correlation between thyroglobulin positivity and grade of differentiation. The immunostaining could not differentiate follicular adenoma from follicular carcinoma. More extensive study using other markers may be useful for better patient management.     

Conjugated linoleic acid decreases hepatic stearoyl-CoA desaturase mRNA expression

Conjugated dienoic derivatives of linoleic acid (CLA) is a collective term for positional and geometric isomers of linoleic acid that occur naturally in foods. The two predominant isomers of CLA are the c9,t11 and t10,c12. One of the effects of CLA is to modify membrane fatty acid composition by decreasing the activity of stearoyl-CoA desaturase enzyme activity. We analyzed the changes of stearoyl-CoA desaturase gene 1 (scd1) mRNA to further define the mechanism for the decrease in Scd enzyme activity by CLA. Mice fed for two weeks with either a fat-free high carbohydrate diet (CHO) or a 5.0% corn oil diet (CO), supplemented with 0.5% CLA had a 45% and 75% decrease respectively, in scd1 mRNA levels in the liver. Consistent with the effects observed in mice, 150 microM CLA suppressed the expression of scd1 mRNA in the H2.35 mouse liver cells by 60%. Further studies with enzymatically prepared c9,t11 isomer showed that the inhibitory effect of CLA on scd1 mRNA expression in H2.35 liver cells was by isomers other than the c9,t11-CLA.     

Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine

The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.     

Effect of lipoxygenase derivatives of linoleic acid on functional activity of neutrophils

The effect of lipoxygenase derivatives of 13-hydroperoxylinoleic acid (13-HPODE) and 13-hydroxylinoleic acid (13-HODE) on zymosan-induced chemiluminescence of rat neutrophils in vitro was evaluated. It was found that both derivatives inhibit functional activity of neutrophils. The extent of inhibition was changed by preincubation of neutrophils with arachidonic or linoleic acid. On the other hand, in experiments with dogs it was shown that the extent of such inhibition considerably increases after ischemia and reperfusion of myocardium. Thus we assume that the ratio of lipoxygenase derivatives of arachidonic and linoleic acid play the regulative role in functional activity of neutrophils. It was concluded, that lipoxygenase derivatives of linoleic acid inhibited the neutrophils functional activity.     

Using survey data to assess neonatal tetanus mortality levels and trends in developing countries

Demographic and health surveys are a useful source of information on the levels and trends of neonatal mortality in developing countries. Such surveys provide data on mortality occurring at 4-14 days of life, which is a sensitive indicator of neonatal tetanus mortality. We analyze birth history data from 37 national surveys in developing countries to assess the quality of neonatal mortality data and to estimate levels and trends in mortality occurring at 4-14 days. It is shown that mortality at 4-14 days has declined considerably during the last decade in most developing countries, concomitant with development and expansion of programs to reduce neonatal tetanus. These declines show that reductions in neonatal tetanus mortality probably have been an important contributor to the decline of neonatal and infant mortality during the 1980s.     

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.