Toxic oil syndrome mortality: the first 13 years. (1/954)

BACKGROUND: The toxic oil syndrome (TOS) epidemic that occurred in Spain in the spring of 1981 caused approximately 20000 cases of a new illness. Overall mortality and mortality by cause in this cohort through 1994 are described for the first time in this report. METHODS: We contacted, via mail or telephone, almost every living member of the cohort and family members of those who were known to have died in order to identify all deaths from 1 May 1981 through 31 December 1994. Cause of death data were collected from death certificates and underlying causes of death were coded using the International Classification of Diseases, 9th Revision. RESULTS: We identified 1663 deaths between 1 May 1981 and 31 December 1994 among 19 754 TOS cohort members, for a crude mortality rate of 8.4%. Mortality was highest during 1981, with a standardized mortality ratio (SMR) of 4.92 (95% confidence interval [CI]: 4.39-5.50) compared with the Spanish population as a whole. The highest SMR, (20.41, 95% CI: 15.97-25.71) was seen among women aged 20-39 years during the period from 1 May 1981 through 31 December 1982. Women <40 years old, who were affected by TOS , were at greater risk for death in most time periods than their unaffected peers, while older women and men were not. Over the follow-up period, mortality of the cohort was less than expected when compared with mortality of the general Spanish population, or with mortality of the population of the 14 provinces where the epidemic occurred. We also found that, except for deaths attributed to external causes including TOS and deaths due to pulmonary hypertension, all causes of death were decreased in TOS patients compared to the Spanish population. The most frequent underlying causes of death were TOS, 350 (21.1%); circulatory disorders, 536 (32.3%); and malignancies, 310 (18.7%). CONCLUSIONS: We conclude that while on average people affected by toxic oil syndrome are not at greater risk for death over the 13-year study period than any of the comparison groups, women <40 years old were at greater risk of death.  (+info)

High-linoleate and high-alpha-linolenate diets affect learning ability and natural behavior in SAMR1 mice. (2/954)

Semipurified diets incorporating either perilla oil [high in alpha-linolenate, 18:3(n-3)] or safflower oil [high in linoleate, 18:2(n-6)] were fed to senescence-resistant SAMR1 mouse dams and their pups. Male offspring at 15 mo were examined using behavioral tests. In the open field test, locomotor activity during a 5-min period was significantly higher in the safflower oil group than in the perilla oil group. Observations of the circadian rhythm (48 h) of spontaneous motor activity indicated that the safflower oil group was more active than the perilla oil group during the first and second dark periods. The total number of responses to positive and negative stimuli was higher in the safflower oil group than in the perilla oil group in the light and dark discrimination learning test, but the correct response ratio was lower in the safflower oil group. The difference in the (n-6)/(n-3) ratios of the diets reflected the proportions of (n-6) polyunsaturated fatty acids, rather than those of (n-3) polyunsaturated fatty acids in the brain total fatty acids, and in the proportions of (n-6) and (n-3) polyunsaturated fatty acids in the total polyunsaturated fatty acids of the brain phospholipids. These results suggest that in SAMR1 mice, the dietary alpha-linolenate/linoleate balance affects the (n-6)/(n-3) ratio of brain phospholipids, and this may modify emotional reactivity and learning ability.  (+info)

Comparative hypocholesterolemic effects of five animal oils in cholesterol-fed rats. (3/954)

The hypocholesterolemic efficacy of various animal oils was compared in rats given a cholesterol-enriched diet. After acclimatization for one week, male F344 DuCrj rats (8 weeks of age) that had been fed with a conventional diet were assigned to diets containing 5% of oil from emu (Dromaius), Japanese Sika deer (Cervus nippon yesoensis, Heude), sardine, beef tallow, or lard with 0.5% cholesterol for 6 weeks. After this feeding period, the concentrations of serum total cholesterol and of very-low-density lipoprotein + intermediate-density lipoprotein + low-density lipoprotein-cholesterol in the sardine oil group were significantly lower than those in the other groups. The serum high-density lipoprotein-cholesterol concentration in the Japanese Sika deer oil group was significantly higher than that in the other groups. The atherosclerotic index and liver cholesterol concentration in the sardine oil and Japanese Sika deer oil groups were significantly lower than those in the other groups. The fecal cholesterol excretion by the Japanese Sika deer oil group was significantly higher than that of the other groups, except for the sardine oil group, and the fecal bile acid excretion by the sardine oil group was significantly higher than that of the other groups, except for the lard group. These results suggest that Japanese Sika deer oil reduced the atherosclerotic index and liver cholesterol concentration in the presence of excess cholesterol in the diet as well as sardine oil did by increasing the excretion of cholesterol from the intestines of rats.  (+info)

Dietary fish oils inhibit early events in the assembly of very low density lipoproteins and target apoB for degradation within the rough endoplasmic reticulum of hamster hepatocytes. (4/954)

Dietary fish oils inhibited secretion and stimulated intracellular degradation of apolipoprotein (apo)B in hamster hepatocytes, while dietary sunflower oils stimulated secretion and had no effect on degradation of apoB. To investigate the intracellular site at which fish oils act, we have made use of our previous observations that inhibition of degradation by N-acetyl-leucyl-leucyl-norleucinal (ALLN) results in accumulation of apoB in the trans -Golgi membrane and does not stimulate secretion, while inhibition of degradation by o-phenanthroline results in accumulation of apoB in the rough endoplasmic reticulum membrane and stimulates secretion. Thus, ALLN protects apoB which has been diverted from secretion and o -phenanthroline protects apoB which is targetted for secretion. Addition of o -phenantholine to the incubation medium of hepatocytes from fish oil-fed hamsters inhibited degradation of apoB and stimulated its secretion in particles of the density of VLDL, while addition of ALLN had no effect. These observations suggest that dietary fish oils reversibly inhibit early steps in the assembly of very low density lipoprotein precursors and target apoB for degradation in the rough endoplasmic reticulum.  (+info)

The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil. (5/954)

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body.  (+info)

Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. (6/954)

We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas-liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10- 46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant sterol proportions by 8-13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.  (+info)

Thyroid hormone status and membrane n-3 fatty acid content influence mitochondrial proton leak. (7/954)

Proton leak, as determined by the relationship between respiration rate and membrane potential, was lower in mitochondria from hypothyroid rats compared to euthyroid controls. Moreover, proton leak rates diminished even more when hypothyroid rats were fed a diet containing 5% of the lipid content as n-3 fatty acids. Similarly, proton leak was lower in euthyroid rats fed the 5% n-3 diet compared to one containing only 1% n-3 fatty acids. Lower proton leaks rates were associated with increased inner mitochondrial membrane levels of n-3 fatty acids and a decrease in the ratio of n-6/n-3 fatty acids. This trend was evident in the phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin phospholipid fractions. These results suggest that a significant portion of the effect of thyroid hormone status on proton leak is due to alterations in membrane fatty acid composition, primarily changes in n-3 content. Both the hypothyroid state and dietary effects appear to be mediated in part by inhibition of the Delta6- and Delta5-desaturase pathways.  (+info)

Bile diversion in rats leads to a decreased plasma concentration of linoleic acid which is not due to decreased net intestinal absorption of dietary linoleic acid. (8/954)

Decreased bile secretion into the intestine has been associated with low plasma concentrations of essential fatty acids (EFA) in humans. We studied the mechanism behind this relationship by determining the status and absorption of the major dietary EFA, linoleic acid (LA), in control and 1-week bile-diverted rats. The absorption of LA was quantified by a balance method and by measuring plasma concentrations of [13C]LA after its intraduodenal administration. Absolute and relative concentrations of LA in plasma were decreased in bile-diverted rats (P<0.01 and P<0.001, respectively). Fecal excretion of LA was increased at least 20-fold in bile-diverted rats (0.72+/-0.11 vs. 0.03+/-0.00 mmol/day; P<0.0001). Due to increased chow ingestion by bile-diverted rats, net intestinal absorption of LA was similar between bile-diverted and control rats (1.96+/-0.14 vs. 1.91+/-0.07 mmol/day, respectively; P>0.05). After intraduodenal administration of [13C]LA, plasma concentrations were approximately 3-4-fold lower in bile-diverted rats for at least 6 h (P<0.001). Plasma concentrations of both [12C]arachidonic acid and [13C]arachidonic acid were increased in bile-diverted rats (P<0.05). We conclude that decreased plasma concentrations of LA in 1-week bile-diverted rats are not due to decreased net intestinal absorption of LA, but may be related to increased metabolism of LA.  (+info)