Do long-chain polyunsaturated fatty acids influence infant cognitive behaviour?

OBJECTIVE: To determine: (i) the proportion of vesicoureteric reflux (VUR) associated with congenital renal damage and whether it can be severe enough to cause renal impairment from birth: (ii) to evaluate the distribution of males and females affected; and (iii) to describe the course of congenital damage in the first years of life. PATIENTS AND METHODS: A total of 108 children (76 male and 32 female, M:F 2.3:1), whose VUR was diagnosed before any infection, were followed from birth for a mean (range) of 4.3 (1-10) years. Renal damage was defined by serum creatinine concentration, creatinine clearance and renal imaging (ultrasonography and renal scintigraphy) performed within the first month of life and periodically thereafter. RESULTS: Of the 108 children, 58 had bilateral and 50 unilateral reflux (total number of refluxing units, 166). High-grade VUR (grade > or = 4) was found in 96 (58%) refluxing renal units (RRUs). Males had a prevalence of bilateral severe (> or = grade 4) reflux (M:F 5.2:1), while in those wit unilateral VUR, the M:F ration was 1.5:1. At birth, mild to moderate damage was present in 56 (36%) RRUs and only associated with VUR of grade > or = 3. Bilateral reflux of grade > or = 4 was associated with congenital moderate/severe renal failure in nine neonates (seven males). In infants with grade > or = 4 VUR who underwent surgical correction, VUR resolved in 92% of cases. In infants with VUR of grade > or = 4 followed medically, the reflux spontaneously resolved in 42% and ameliorated in 16% after 18 months. Serial renal scans during the follow-up showed no progression of renal damage. CONCLUSIONS: VUR diagnosed at birth on prenatal ultrasonography is associated with congenital damage, with males affected more often than females. The damage involves both kidneys in a consistent proportion and is an important cause of chronic renal impairment from birth. It does not progress in the first years of life if infections are prevented. It is suggested that males with this condition may constitute a major group at risk of developing chronic renal failure in later life.     

Modification of milk formula to enhance accretion of long-chain n-6 and n-3 polyunsaturated fatty acids in artificially reared infant rats

Background spike activity of 235 cells of the integrative subcortical motor center, i.e., the ventrolateral nucleus of the thalamus, were analyzed in nonanesthetized human brains during stereotaxic surgery in patients with various forms of Parkinson's disease. Previous data on the existence of two major types of neurons with convergent properties in the ventrolateral nucleus were confirmed. These cell types are: 1) cells with irregular occasional activity, with a tendency for spikes to group into the frequency ranges 5 +/- 1 and 10-30 Hz (type A cells, 74%), and 2) cells with constant rhythmic (3-6 Hz) generation of short volleys of discharges, with an interval structure similar to that of low-threshold Ca(2+)-dependent volley activity (type B, 26%). This is the first report demonstrating that changes in the functional state of the brain (after repeated movement trials, in transient anesthesia) are accompanied by transiently occurring transformations of the initial irregular activity of A cells into a rhythmic, volley-like pattern whose interval structure was in some cases similar to the spike activity of B cells. Differences in the localizations of A and B neurons in the ventrolateral nucleus are described, along with differences in the correlation characteristics of their background spike activity with the pathological features of Parkinson's disease (tremor, rigidity). The nature of the two types of convergent neurons in the ventrolateral nucleus is discussed, and a basis is laid for the importance of the functional factor in understanding the transformation of their background spike activity, due to the properties of cell membranes and intercellular and interstructure interactions in conditions of the living nonanesthetized human brain.     

Plasma and erythrocyte alpha-tocopherol and plasma retinol concentrations in term infants fed formula enriched with long-chain polyunsaturated fatty acids

OBJECTIVE: To assess the effect of long-chain polyunsaturated fatty acids (LCPUFA)- and vitamin E-supplemented formula feeding on erythrocyte and plasma alpha-tocopherol (VE), and plasma retinol (VA) concentrations in neonates and to compare these values with those found in infants feeding on infant formula without LCPUFA or breast milk SETTING: University Hospital of Granada, Spain. SUBJECTS: 49 full-term infants. DESIGN AND INTERVENTION: Subjects who chose not to breast feed were fed either (i) unsupplemented infant formula (F) or (ii) infant formula supplemented with LCPUFA and vitamin E (FL). Alpha-tocopherol and retinol were measured at 7 days, 1 month and 3 months. RESULTS: Plasma and erythrocyte VE concentrations and plasma VE/total lipids ratio increased significantly in all groups at 1 month of life (P < 0.05), but did not change significantly between 1 month and 3 months in any group (P > 0.05). Erythrocyte VE and VA retinol concentrations were higher in infants fed an infant formula than in breast milk-fed infants at 1 month of life (P < 0.05). Finally, there were no significant differences in plasma or erythrocyte VE levels, plasma VA or plasma VE/total lipid ratio between any groups at 3 months of life (P > 0.05). CONCLUSION: Infants fed on LCPUFA- and vitamin E-supplemented infant formula for 3 months have similar vitamin E and A status to infants fed on breast milk or infant formula without LCPUFA supplementation.     

Peroxisomal beta-oxidation of polyunsaturated fatty acids

Peroxisomes have been shown to play an important role in the oxidative degradation of (poly)unsaturated fatty acids, and contain the enzyme activities needed for the metabolism of double bonds of unsaturated fatty acids in connection with this physiological function. Our understanding of the metabolic pathways and enzyme activities involved in the degradation of unsaturated acyl-CoAs has undergone a re-evaluation recently, and though many open questions still remain significant progress has been made, especially concerning the reactions metabolizing double bonds. The enzyme activities to be discussed here are 2,4-dienoyl-CoA reductase; 3/2-enoyl-CoA isomerase; 2-enoyl-CoA hydratase 2; 5-enoyl-CoA reductase and 3,5/2,4-dienoyl-CoA isomerase. Some of these activities are integral parts of the multifunctional proteins of beta-oxidation systems, which must also be taken into account in this context.     

Docosahexaenoic acid concentrations in retinal phospholipids of piglets fed an infant formula enriched with long-chain polyunsaturated fatty acids: effects of egg phospholipids and fish oils with different ratios of eicosapentaenoic acid to docosahexaenoic acid

The purpose of our study was the assessment of the diagnostic value of vacuum core biopsy, which promises high accuracy by minimally invasive percutaneous excision of 1-2 cm3 of tissue. The materials used were a digital stereotaxic biopsy table (Fischer Imaging) and a Mammotome-gun (Biopsys). A total of 236 patients with 261 predominantly indeterminate lesions (indeterminate: 230; suspicious: 26; malignant: 5) underwent vacuum core biopsy (VCB). Verification was as follows: (a) demonstration of complete or partial removal of the lesion or replacement of the lesion by a small hematoma by comparison of the pre- and post-VCB mammogram; (b) reexcision of 45 malignant and 6 borderline lesions; (c) radiologic-histologic correlation; and (d) 6-month-follow-up mammograms in 129 cases. Two VCBs were not possible because very fine microcalcifications could not be visualized. Two puncture errors occurred which, however, were immediately recognized and VCB was repeated. Based on the above verification a 100 % accuracy was achieved. No relevant side effects occurred. Except for 2 cases mammographically hardly any scarring was visible. Based on the excellent accuracy and excellent tolerance of the procedure VCB appears to be the future method of choice for the workup of those indeterminate mammographically detected lesions that up to now have still required surgical biopsy.     

Polyunsaturated fatty acids in infant nutrition

The availability of long-chain polyunsaturated fatty acids (LCP), such as arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acids, is important for early human growth and development. The capacity for endogenous synthesis of LCP from the precursor fatty acids linoleic (C18:2n-6) and alpha-linolenic (C18:3n-3) acid is limited in preterm and probably also in term infants. In utero, LCPs seem to be transferred preferentially from the mother to the foetus by the placenta. After birth, breast-fed infants receive preformed dietary LCP with human milk. In contrast, most current infant formulae are devoid of LCP. Premature infants fed such formulae develop rapid LCP depletion of plasma and tissue lipids, which is associated with reduced visual acuity during the first postnatal months. Therefore, LCP enrichment of formulae for premature infants is desirable. Recent observations indicate that term infants fed conventional formulae also exhibit lower plasma LCP values and may show functional disadvantages, but these data require further confirmation prior to drawing definite conclusions.     

Influence of administration of long-chain polyunsaturated fatty acids on process of histological recovery in liver cirrhosis produced by oral intake of thioacetamide

Patients with liver cirrhosis frequently show some degree of protein-energy malnutrition and obviously require nutritional support. In this study, the treatment of rats consisted of the ad libitum oral intake of a 300 mg/liter thioacetamide solution, used as drinking water for four months. Thioacetamide treatment produced a severe alteration in the plasma fatty acid profile with significant decreases of these, which mimicked changes described in human cirrhosis. This hepatotoxic agent causes nodular cirrhosis, with loss of the normal architecture of the liver and disruption of the vascular pattern. The goal of the study was to evaluate the influence of n-3 and n-6 series long-chain polyunsaturated fatty acid dietary supplementation in experimental animals and to assess the effects of those dietary components on structural recovery in the liver. Significant increases of saturated and monounsaturated fatty acids as well as n-6 polyunsaturated fatty acids were seen only in the animals given the n-6 polyunsaturated fatty acid supplemented diet. However, only rats given the standard diet exhibited some degree of histological regeneration.     

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)     

Long chain W3 polyunsaturated fatty acids and lipid pattern in the mother and the newborn infant

The ratio of oxygen to carbon monoxide binding to the three fully saturated human embryonic hemoglobins has been determined. The embryonic hemoglobins exhibit significantly lower values of carbon monoxide binding than any previously reported mammalian fetal or adult hemoglobins. The possible protective role of this with regards to carbon monoxide intoxication is discussed. These data are combined with previous parameters yielding a significant correlation between oxygen affinity and carbon monoxide binding. A possible molecular origin of this correlation is discussed.     

Modulation of exercise-induced immunosuppression by dietary polyunsaturated fatty acids in mice

The possible interaction between intense exercise, known to suppress the immune response, and nutritive factors, such as polyunsaturated fatty acids (PUFA), was examined in inbred female C57Bl/6 mice. The animals received for 8 wk either a natural ingredient diet or a diet supplemented with 10 g/100 g linseed oil containing over 50% of 18:3 (n-3) alpha-linoleic acid. Other groups received PUFA containing only traces of 18:3 (n-3) fatty acid; beef tallow, containing mostly 18:1 (n-9) saturated fat, safflower oil, an 18:2 (n-6) PUFA, and fish oil, containing longer chain (n-3) PUFA. Each dietary group was divided into two subgroups: sedentary diet controls and exercised animals. Exercise consisted of continuous swimming at high intensity until exhaustion. It was shown in three separate experiments that (1) the primary humoral response to sheep red blood cells, determined by the plaque-forming cell (PFC) assay, was affected by PUFA diet in sedentary animals in the order beef tallow > control diet > safflower oil > fish oil > linseed oil, and (2) the PFC response was suppressed by the exhaustive exercise, as compared to sedentary controls, except for animals fed 18:3 (n-3) linseed oil, where the normal response was noted. Phagocytosis of fluorescent microspheres by peritoneal macrophages, determined by flow cytometry, was significantly lower in exercised animals receiving the linseed oil diet, whereas other diets either increased or did not significantly change the macrophage phagocytic activity, compared to the sedentary diet controls. Spleen lymphocyte subsets were unchanged in exercised animals except for a marked shift from the lymphoid peak toward the erythroid peak. Generally, our data showed a marked immunomodulatory effect of 18-3 (n-3) alpha-linoleic acid on the exhaustive exercise-related immunosuppression, as compared to the effects of other selected PUFA.     

Hypoantigenic (HA) milk formula and blood cholesterol level in infants at 3 months of age

A preliminary observation is reported concerning total and high-density lipoprotein blood cholesterol levels in 36 infants at 3 months of age fed with a hypoantigenic milk formula. The values are compared with those of 66 breastfed and 76 conventional formula-fed infants. Total and high-density lipoprotein-cholesterol levels in hypoantigenic formula-fed infants (152 and 65.7 mg dl(-1), respectively) were comparable to those of breastfed infants (148 and 61.8 mg dl(-1)) and significantly (p < 0.05) higher than those of conventional formula-fed infants (130 and 42.5 mg dl(-1)).     

Omega-3 polyunsaturated fatty acids in rodent models of breast cancer

Quantitative increases in certain dietary fats promote mammary tumor growth, but the experimental data indicate that this tumor promoting capability is not equally expressed by all fatty acid families. There is a large body of evidence from experiments using either carcinogen-induced or transplanted animal mammary tumor models, as well as in vitro studies, which demonstrates that the omega-6 polyunsaturated fatty acids (PUFA) promote mammary tumor development more effectively than omega-3 PUFA. These data indicate that increases in the dietary levels of omega-6 PUFA enhance tumor development, while equivalent increases in dietary levels of omega-3 PUFA often delay or reduce tumor development. Several theoretical mechanisms have been proposed for these contrasting results, but as yet, no definitive explanation has been universally accepted.     

The benefits and risks of n-3 polyunsaturated fatty acids

There is a growing number of animal models and clinical trials of n-3 polyunsaturated fatty acid (PUFAs) supplementation in disease. Epidemiologic and biochemical studies have suggested beneficial effects of n-3 PUFAs. But also, the use of n-3 PUFAs has some potential toxicological risks that can be circumvented by careless processing, storing, and preserving the PUFAs. The use of n-3 PUFAs is safe if appropriate preparations and dosages are selected. Much research is needed to clarify their use under different disease conditions. The newly established clinical and nutritional facts on n-3 PUFAs will induce industry to develop food products based on this knowledge.     

Incorporation of n-3 polyunsaturated fatty acids into processed foods

The aim of dose reduction of chemotherapeutic agents following weight loss is to avoid excessive toxicity while maintaining an equivalent therapeutic effect. Several methods of calculating this dose reduction are currently in use, including dose reduction in proportion to the reduction in body surface area (BSA) or the amount of weight lost and no dose reduction unless significant toxicity occurs. Each of these methods results in the administration of a different dose and therefore different drug exposure, as measured by the area under the time versus concentration curve (AUC). We have used pharmacokinetic modeling software and normative data on the pharmacokinetics of high-dose methotrexate to determine the change in AUC resulting from dose reduction by each of the methods cited for patients with weight loss. Dose reduction in proportion to the reduction in weight results in the same AUC and therefore equivalent drug exposure as before weight loss. In contrast, the more common practice of dose reduction in proportion to the decrease in BSA (as determined by recalculating BSA) results in a higher AUC than before weight loss. This results in increased drug exposure and potentially increased toxicity, which may be avoided if dose reduction is carried out in proportion to the decrease in weight rather than in BSA. The same principles are applicable to other drugs, particularly those associated with dose-dependent toxicity.     

Regulation of tumour cell fatty acid oxidation by n-6 polyunsaturated fatty acids

The aim of this study was to evaluate acute effects of ethyl tert-butyl ether (ETBE) in man after short-term exposure. ETBE may in the future replace methyl tert-butyl ether, a widely used oxygenate in unleaded gasoline. Eight healthy male volunteers were exposed to ETBE vapor for 2 h at four levels (0, 5, 25, and 50 ppm) during light physical exercise. The subjects rated irritative symptoms, discomfort, and central nervous system effects in a questionnaire. Ocular (eye redness, tear film break-up time, conjunctival epithelial damage, and blinking frequency), nasal (acoustic rhinometry and analysis of inflammatory markers and cells in nasal lavage fluid), and pulmonary (peak expiratory flow, forced expiratory volume in 1 s, forced vital capacity, vital capacity, and transfer factor) measurements were performed. Significantly increased ratings of solvent smell (p = 0.001, repeated-measures ANOVA) were seen during exposures and correlated to exposure levels. Furthermore, significantly elevated ratings of discomfort in throat and airways were seen during and after 50 ppm compared to the control exposure (p = 0.02). Increased nasal swelling (p = 0.001) and blinking frequency (p = 0.01) were noted at all exposure levels, but their magnitudes were not related to exposure levels. A slightly impaired pulmonary function was seen at 25 and 50 ppm, since forced vital capacity (p = 0.02) and vital capacity (p = 0.04) differed significantly from the clean air exposure. Although the impairments seemed to fall within normal inter- and intraindividual variation and have no clinical relevance as such, it cannot be excluded that other individuals may react more severely than eight healthy male volunteers in this study.     

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.     

n-3 versus n-6 polyunsaturated fatty acids in critical illness

The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0 +/- 3.2 and 10.9 +/- 2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and 'Articular Disease Severity Score' (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry. BMD of the patients at the lumbar spine was significantly lower than the control group (p < 0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.     

Everyday problem solving in adulthood and old age.

We examined everyday problem solving in adulthood and compared it with traditional measures of cognitive abilities. In the first phase of the research, we describe the construction of an inventory to assess problem solving in situations that adults might encounter in everyday life and examine raters' judgments of effective responses to the problems. In the second phase, adults (N?=?126) between the ages of 20 and 78 were administered the inventory and tests of verbal and abstract problem-solving abilities. Results indicated modest but significant positive correlations between performance on the inventory and traditional ability tests. The examination of age differences revealed that performance on the Everyday Problem-Solving Inventory and verbal ability test increased with age, whereas performance on a traditional problem-solving test declined after middle age. In addition, education was unrelated to everyday problem solving, highly related to verbal ability, and moderately related to traditional problem solving. Results are discussed in relation to pluralistic conceptions of intelligence and theories of adult intellectual development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)