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Biomedical subjects

J M Wallace

Publications and source records attributed to J M Wallace.

At least 19 recordsLinked to original sources

Nutritional modulation of adolescent pregnancy outcome -- a review.

The risks of miscarriage, prematurity and low birth weight are particularly acute in adolescent girls who are still growing at the time of conception. The role of maternal nutrition in mediating pregnancy outcome in this vulnerable group has been examined in sheep models. When singleton bearing adolescent dams are overnourished to promote rapid maternal growth throughout pregnancy, growth of both the placenta and fetus is impaired, and birth occurs prematurely relative to control adolescents of equivalent age. Studies at mid-gestation, prior to alterations in placental mass, suggest that reduced proliferation of the fetal trophectoderm, impaired angiogenesis, and attenuated uteroplacental blood flows are early defects in placental development. By late pregnancy, relative placental mass is reduced by 45% but uteroplacental metabolism and placental glucose transfer capacity remain normal when expressed on a placental weight specific basis. The asymmetrically growth-restricted fetuses are hypoxic, hypoglycemic and have reduced insulin and IGF-1 concentrations. Absolute umbilical nutrient uptakes are attenuated but fetal utilisation of glucose, oxygen and amino acids remains normal on a fetal weight basis. This suggests altered sensitivities to metabolic signals and may have implications for subsequent metabolic health. At the other end of the nutritional spectrum, many girls who become pregnant have inadequate or marginal nutritional status during pregnancy. This situation is replicated in a second model whereby dams are prevented from growing during pregnancy by relatively underfeeding. Limiting maternal intake in this way gradually depletes maternal body reserves leading to a lower transplacental glucose gradient and a modest slowing of fetal growth in late pregnancy. These changes appear to be independent of alterations in placental growth per se. Thus, while the underlying mechanisms differ, maternal intake at both ends of the nutritional spectrum is a powerful determinant of fetal growth in pregnant adolescents.

Adolescent↗

Board-invited review: intrauterine growth retardation: implications for the animal sciences.

Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.

Animal Husbandry↗

Investigating the causes of low birth weight in contrasting ovine paradigms.

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis and uteroplacental blood flow appears to be an early defect in both the hyperthermic and adolescent paradigms. The effects of these alterations in placental functional development appear to be irreversible. IUGR fetuses are both hypoxic and hypoglycaemic, and have reduced insulin and insulin-like growth factor-1 (IGF-1), and elevated concentrations of lactate. However, fetal utilization of oxygen and glucose, on a weight basis, remain constant compared with control pregnancies. Maintained utilization of these substrates, in a substrate-deficient environment, suggests increased sensitivities to metabolic signals, which may play a role in the development of metabolic diseases in later adult life.

Animals↗

The effects of acute nutrient restriction in the mid-gestational ewe on maternal and fetal nutrient status, the expression of placental growth factors and fetal growth.

This study explores the hypothesis that acute under-nutrition in mid-gestation reduces maternal and fetal nutrient status and affects the expression of specific regulators of placental growth and function. Welsh Mountain ewes were fed a concentrate diet plus wheat straw to provide 100% of their maintenance requirements. The concentrate ration of nutrient restricted (NR) ewes was reduced from day (d) 83 of gestation and withdrawn from d85 to d90. At d90, half the ewes (NR m = 7, control n = 8) were euthanased. The remainder (NR n = 9, control n = 9) were fed their maintenance diet until slaughter at d135. Maternal plasma insulin and IGF-I concentrations decreased during nutrient restriction and NEFA concentrations increased. Fetal IGF-I and insulin concentrations were unaltered by maternal diet. Placental VEGF mRNA expression was reduced at d90 (P < 0.05). IGFBP-3 and IGFBP-2 mRNA expression was reduced at d90 (P < 0.05) and d135 (P < 0.05), respectively. Placental weight was significantly lower in NR ewes at d90 (P < 0.05) and the distribution of placentomes shifted towards the everted phenotype at d135 (P < 0.05). Reduced thoracic girth and uterine fluid volume at d90 (P < 0.05) and decreased fetal lung weight at d90 (P < 0.05) and d135 (P < 0.05) suggest spatial limitation of lung expansion. In summary, acute NR in mid-gestation reduced anabolic drive and mobilised lipid stores in the maternal compartment, whilst fetal nutrient status was maintained. This was accompanied by changes in placental VEGF and IGFBP expression. The growth of the fetal lung appears to have been compromised and this may have adverse consequences for subsequent neonatal respiratory function.

Animals↗

Animal models of placental angiogenesis.

The study of the development of the fetal membranes is an ancient one, and the importance of placental vascular development to placental function has long been recognized. Animal models have been important in these studies, as they allow for controlled experiments and analysis of multiple time-points during pregnancy. Since the demonstration nearly 20 years ago that the placenta produces angiogenic factors, the major factors regulating placental angiogenesis have been identified. These major factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), the angiopoietins (ANG), and their receptors. Recently, sophisticated computerized image analysis methods have been developed to establish the pattern of placental vascular development in sheep. The maternal placental capillary bed develops primarily by increased size of capillaries, with only small increases in capillary number or surface densities. In contrast, the microvasculature of the fetal placenta develops primarily by increased branching, resulting in a large increase in capillary number and surface densities. These observations help to explain the relatively large increase in umbilical blood flow and nutrient delivery to the fetus that occurs during the last half of gestation. In addition, expression of mRNAs for VEGF, bFGF, ANG, and their receptors have recently been correlated with normal placental vascular development in sheep, and further refinement of these mathematical models is warranted. Lastly, the recent development of animal models of compromised pregnancies, including those resulting from maternal nutrition (both restriction and excess), multiple fetuses, environmental stress (heat stress and high altitude), and fetal and maternal breed effects, has already indicated that reductions in placental vascular development and expression of angiogenic factors are probably a root cause of fetal growth restriction. With these methods and models now in place, we should soon be able to establish the mechanisms involved in both normal and abnormal placental angiogenesis.

Angiopoietins↗

Effect of nutrient intake during pregnancy on fetal and placental growth and vascular development.

Remarkable diversity of size and health of offspring exists after normal pregnancies. When pregnancies are complicated by an extrinsic variable such as inappropriate maternal nutrition, birth weight and health of the neonate are substantially affected. The placenta is the organ through which respiratory gases, nutrients, and wastes are exchanged between the maternal and fetal systems. Thus, transplacental exchange provides for all the metabolic demands of fetal growth. Transplacental exchange is dependent upon uterine and umbilical blood flow, and blood flow rates are in turn dependent in large part upon vascularization of the placenta. Therefore, factors that influence placental vascular development will have a dramatic impact on fetal growth and development, and thereby on neonatal mortality and morbidity. Recent work from our laboratories has focused on the effects of nutrient intake during pregnancy on placental growth and vascular development. Both nutrient restriction of the adult dam and overnourishment of the adolescent dam during pregnancy suppress placental cell proliferation and vascularity. Furthermore, placental expression of angiogenic factors and their receptors, factors that are known to affect vascular growth, are perturbed by level of nutrition. Studies in this area will lead to improved methods to manage nutritionally-compromised pregnancies.

Animal Nutritional Physiological Phenomena↗

Abrupt climate change.

Large, abrupt, and widespread climate changes with major impacts have occurred repeatedly in the past, when the Earth system was forced across thresholds. Although abrupt climate changes can occur for many reasons, it is conceivable that human forcing of climate change is increasing the probability of large, abrupt events. Were such an event to recur, the economic and ecological impacts could be large and potentially serious. Unpredictability exhibited near climate thresholds in simple models shows that some uncertainty will always be associated with projections. In light of these uncertainties, policy-makers should consider expanding research into abrupt climate change, improving monitoring systems, and taking actions designed to enhance the adaptability and resilience of ecosystems and economies.

Journal Article↗

Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes.

Overnourishing adolescent ewes throughout pregnancy promotes maternal tissue synthesis at the expense of placental growth, which in turn leads to a major decrease in lamb birth weight. As maternal dietary intakes are inversely related to peripheral progesterone concentrations in these adolescent dams, it was hypothesized that sup-optimal progesterone concentrations in overnourished dams may compromise the growth of the differentiating conceptus resulting in fewer uterine caruncles being occupied and, hence, fewer placentomes formed. This hypothesis was tested by supplementing overnourished adolescent dams with exogenous progesterone during early pregnancy and determining the impact on pregnancy outcome at term. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. After transfer of embryos, ewes were offered a moderate or high amount of a complete diet (n=11 per group). A further high intake group received a progesterone supplement each day from day 5 to day 55 of gestation (term=145 days) to restore circulating progesterone concentrations to moderate values throughout the first third of pregnancy (n=11). For ewes establishing pregnancies (n=7 per group), live weight gain during the first 100 days of gestation was 66+/-4, 323+/-17 and 300+/-7 g per day, body condition score at term was 2.1+/-0.05, 3.0+/-0.08 and 3.1+/-0.07 units and the duration of gestation after spontaneous delivery was 148+/-1.7, 144+/-0.8 and 143+/-0.8 days for the moderate intake, high intake and high intake plus progesterone groups, respectively. At delivery, fetal cotyledon mass (136+/-12.1 versus 57+/-8.2g, P<0.001) and lamb birth weight (5164+/-151 versus 2893+/-381 g, P<0.001) were higher in moderate intake than in high intake dams. Progesterone supplementation restored circulating concentrations to moderate values during the first third of gestation. Lamb birth weight in the high intake plus progesterone group (4150+/-389 g) was intermediate between the high intake (P<0.02) and moderate intake (P<0.05) groups, but this change in birth weight was not associated with corresponding changes in fetal cotyledon mass (76+/-10.3 g). Moreover, the number of fetal cotyledons was similar in all three groups. Thus, progesterone did not directly affect the growth of the fetal cotyledon but may have influenced placental vascularity, blood flow or nutrient transfer capacity or alternatively the development of the embryonic inner cell mass.

Animals↗

Intracranial lymphomas in simian retrovirus-positive Macaca fascicularis.

Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. I for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.

Animals↗

Impact of maternal nutrition during pregnancy on pituitary gonadotrophin gene expression and ovarian development in growth-restricted and normally grown late gestation sheep fetuses.

The influence of maternal nutrition during pregnancy on anterior pituitary gonadotrophin gene expression and ovarian development in sheep fetuses during late gestation was investigated. Embryos recovered from superovulated adult ewes that had been inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After embryo transfer, adolescent ewes were offered a high or moderate amount of a complete diet. Pregnancies were terminated at day 131 +/- 0.6 of gestation and the fetal brain, anterior pituitary gland and gonads were collected. Gonadotrophin gene expression (LHbeta and FSHbeta subunits) in the fetal pituitary gland was examined using in situ hybridization. Ovarian follicular development was quantified in haematoxylin- and eosin-stained ovarian sections embedded in paraffin wax. Six dams that were offered a high nutrient intake carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet) and 13 dams carried growth-restricted fetuses (weight <or= +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet). Mean placental masses in these groups were 354 +/- 24.5 and 230 +/- 21.1 g, respectively, compared with 442 +/- 54.3 g in the dams that were offered a moderate nutrient intake (n = 6). Growth-restricted fetuses from dams offered a high nutrient intake showed higher pituitary LHbeta mRNA expression (P < 0.05) than normal-sized fetuses from dams offered a moderate nutrient intake (252 +/- 21.6 and 172 +/- 23.6 nCi g(-1), respectively). FSHbeta mRNA expression was not influenced by growth status. Fewer follicles (primarily in the resting pool) were observed in the ovaries of both growth-restricted (P < 0.002) and normal-sized fetuses from dams offered a high nutrient intake (P < 0.01) compared with normal-sized fetuses from dams offered a moderate nutrient intake. Irrespective of nutritional treatment, the total number of follicles was positively associated with placental mass (P < 0.01). Thus, a high maternal nutrient intake during adolescent pregnancy had a negative influence on ovarian follicular development in fetuses as determined during late gestation.

Animal Nutritional Physiological Phenomena↗

Regional climate impacts of the Northern Hemisphere annular mode.

The Northern Hemisphere annular mode (NAM) (also known as the North Atlantic Oscillation) is shown to exert a strong influence on wintertime climate, not only over the Euro-Atlantic half of the hemisphere as documented in previous studies, but over the Pacific half as well. It affects not only the mean conditions, but also the day-to-day variability, modulating the intensity of mid-latitude storms and the frequency of occurrence of high-latitude blocking and cold air outbreaks throughout the hemisphere. The recent trend in the NAM toward its high-index polarity with stronger subpolar westerlies has tended to reduce the severity of winter weather over most middle- and high-latitude Northern Hemisphere continental regions.

Journal Article↗

Susceptibility of LDL to oxidative modification in healthy volunteers supplemented with low doses of n-3 polyunsaturated fatty acids.

The objective of the present study was to evaluate the oxidative susceptibility of LDL in human volunteers following supplementation with various low doses (<1 g/d) of n-3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers (thirty-seven males and twenty-five females, aged 19-63 years) were recruited to take part in a randomised placebo-controlled trial. Volunteers were required to take 0.9, 0.6 or 0.3 g n-3 PUFA as fish oil or placebo capsules daily for 16 weeks. Susceptibility of LDL to oxidative modification was assessed by measuring the production of conjugated dienes and thiobarbituric acid-reactive substances in LDL oxidised by Cu2+ (15 microM) or 2,2'-azobis(2-amidinopropane) dihydrochloride (1 mM) for 5 h. Plasma fatty acid and LDL-fatty acid composition, cholesterol levels and antioxidant concentrations were also measured. While post-treatment n-3 PUFA compositions of plasma and LDL reflected the capsule contents, no meaningful differences in antioxidant concentrations or cholesterol levels were observed between the groups. Supplementation with low doses of n-3 PUFA as fish oil did not influence the oxidative susceptibility of LDL. The results of the present study suggest that moderate dietary intakes of n-3 PUFA do not significantly influence the susceptibility of LDL to oxidative modification in vitro.

Adult↗

Influence of placentally mediated fetal growth restriction on the onset of puberty in male and female lambs.

The onset of puberty in prenatally growth-restricted versus normally grown lambs of both sexes, born in April and housed under natural photoperiod, was examined. Singleton pregnancies were established and adolescent ewes were offered a high or moderate nutrient intake throughout gestation. Placental mass was reduced (P < 0.001) in high compared with moderate intake dams and resulted in the birth of growth-restricted and normal birth weight offspring, respectively. At birth, female lambs weighed 3.43 kg versus 5.03 kg (P < 0.001; n = 14 per group) and male lambs weighed 2.75 kg versus 5.18 kg (P < 0.001; n = 7 per group) in growth-restricted and normal birth weight groups, respectively. Lambs suckled for 12 weeks and thereafter were fed ad libitum until week 43 of age. Growth-restricted lambs had lower preweaning live weight gains and this difference was more pronounced in male (P < 0.05) than in female lambs (P = 0.07). Thereafter, live weight remained lower (P < 0.05) in growth-restricted than in normally grown lambs of both sexes until week 25 of age. In females, the time of onset of puberty was similar in the two groups. All females ovulated and there were no differences in the number of ovarian cycles recorded or in the incidence of aberrant ovarian function. In males, testosterone concentrations and testicular volume were lower in growth-restricted compared with normally developed lambs from birth until weeks 28 and 35 of age, respectively (P < 0.05). The seasonal increase in plasma testosterone concentrations occurred later in growth-restricted than in normally developed lambs (P < 0.01) but the timing of maximum peak concentrations was similar. Peak testosterone concentrations were lower (P < 0.05) in growth-restricted than in normal male lambs.

Aging↗

Circulating leptin during ovine pregnancy in relation to maternal nutrition, body composition and pregnancy outcome.

This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.

Adipose Tissue↗

Can ozone depletion and global warming interact to produce rapid climate change?

The atmosphere displays modes of variability whose structures exhibit a strong longitudinally symmetric (annular) component that extends from the surface to the stratosphere in middle and high latitudes of both hemispheres. In the past 30 years, these modes have exhibited trends that seem larger than their natural background variability, and may be related to human influences on stratospheric ozone and/or atmospheric greenhouse gas concentrations. The pattern of climate trends during the past few decades is marked by rapid cooling and ozone depletion in the polar lower stratosphere of both hemispheres, coupled with an increasing strength of the wintertime westerly polar vortex and a poleward shift of the westerly wind belt at the earth's surface. Annular modes of variability are fundamentally a result of internal dynamical feedbacks within the climate system, and as such can show a large response to rather modest external forcing. The dynamics and thermodynamics of these modes are such that strong synergistic interactions between stratospheric ozone depletion and greenhouse warming are possible. These interactions may be responsible for the pronounced changes in tropospheric and stratospheric climate observed during the past few decades. If these trends continue, they could have important implications for the climate of the 21st century.

Journal Article↗

Health risk and inequitable distribution of liquor stores in African American neighborhood.

In this paper we examine whether the physical availability of alcohol is greater in predominantly African American communities compared to predominantly white communities as indicated by the presence of off premises liquor stores. We investigate the extent to which the income status of the residents of a community mediates the relationship between community racial composition and alcohol availability; and explore whether the intersection of race and class places low income African American communities at increased risk to have such stores located in their communities. Multivariate analytic techniques are used to examine the relationship between community racial composition, median income of neighborhood residents and per capita number of alcohol outlets in 194 census tracts in Baltimore, Maryland. The analysis found that liquor stores are disproportionately located in predominantly black census tracts, even after controlling for census tract socioeconomic status. Census tracts that are both low income and predominantly African American have substantially more liquor stores per capita than other census tracts. Although it is beyond the scope of the present study, our data reveal significant associations between the presence of liquor stores and the risk of health-related social problems in low income neighborhoods. More research needs to be done on the impact of alcohol on the social, psychological, and physiological health of low income urban populations.

Black or African American↗

Nutrient partitioning during pregnancy: adverse gestational outcome in overnourished adolescent dams.

Appropriate nutrient partitioning between the maternal body and gravid uterus is essential for optimum fetal growth and neonatal survival, and in adult sheep nutrient partitioning during pregnancy generally favours the conceptus at the expense of the dam. However, recent studies using an overnourished adolescent sheep model demonstrate that the hierarchy of nutrient partitioning during pregnancy can be dramatically altered in young growing females. Overnourishing the adolescent dams to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass and leads to a significant decrease in birth weight relative to moderately-fed adolescents of equivalent gynaecological age. High maternal feed intakes are also associated with an increased incidence of non-infectious spontaneous abortion, a reduction in gestation length and colostrum production, and a higher incidence of neonatal mortality. The present paper examines the putative role of a variety of endocrine regulators of nutrient partitioning in this unusual model system, where the dam is overnourished while the stunted placenta restricts nutrient supply to the fetus. The central role of nutritionally-mediated alterations in placental growth and development in setting the subsequent pattern of nutrient partitioning between the maternal body, placenta and fetus is examined, and critical periods of sensitivity to alterations in maternal nutritional status are defined. Finally, the consequences of this form of inappropriate nutrient partitioning on the growth and development of the fetus and neonate are described with particular emphasis on the reproductive axis.

Adolescent↗

The effect of low-dose fish oil supplementation on serum growth factors in healthy humans.

OBJECTIVE: To examine the effect of low-dose fish oil supplementation on specific growth factors, purported to play a central role in lesion formation, and also on the total growth factor activity of serum, as assessed by the induction of DNA synthesis in cultured human arterial smooth muscle cells. DESIGN: Randomized placebo-controlled double-blind intervention study. SETTING: Free-living population. SUBJECTS: Sixty-three healthy volunteers, 37 males and 26 females. INTERVENTIONS: Four treatment regimes with subjects receiving 0, 0.3,0.6 or 0.9 g/day of n-3 PUFA for an 8 week period. Blood samples were taken at baseline and following the 8 week intervention. All samples were analysed in batch following completion of the study. RESULTS: Consumption of fish oil had no effect on serum platelet-derived growth factor (PDGF), or transforming growth factor beta (TGFbeta) concentration. Furthermore, fish oil supplementation did not alter the total growth factor activity of serum. CONCLUSIONS: Results indicate that low-dose fish oil supplementation, equivalent to about two portions of fatty fish per week and providing less than 1 g n-3 PUFA/day, does not alter the levels of the major serum growth factors and does not modify total serum growth factor activity in healthy human volunteers. SPONSORSHIP: European Union shared cost project (FAIR-CT-95-0085).

Adult↗