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Biomedical subjects

R A Gibson

Publications and source records attributed to R A Gibson.

At least 37 records · Page 2Linked to original sources

Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation.

Much interest has been expressed about the long-chain polyunsaturated fatty acid (LCPUFA) requirements of both preterm and term infants, whereas relatively little attention has been given to the LCPUFA needs of mothers, who may provide the primary source of LCPUFAs for their fetuses and breast-fed infants. Although maternal requirements for LCPUFAs are difficult to estimate because of large body stores and the capacity to synthesize LCPUFAs from precursors, biochemical and clinical intervention studies have provided some clues. From a biochemical viewpoint, there appears to be no detectable reduction in plasma n-3 LCPUFA concentrations during pregnancy, whereas there is a clear decline during the early postpartum period. The postpartum decrease in maternal plasma docosahexaenoic acid (DHA) concentration is not instantaneous, may be long-term, is independent of lactation, and is reversible with dietary DHA supplementation (200-400 mg/d). From a functional standpoint, the results of randomized clinical studies suggest that n-3 LCPUFA supplementation during pregnancy does not affect the incidences of pregnancy-induced hypertension and preeclampsia without edema. However, n-3 LCPUFA supplementation may cause modest increases in the duration of gestation, birth weight, or both. To date, there is little evidence of harm as a result of n-3 LCPUFA supplementation during either pregnancy or lactation. However, researchers need to further elucidate any potential benefits of supplementation for mothers and infants. Careful attention should be paid to study design, measurement of appropriate health outcomes, and defining minimum and maximum plasma n-3 LCPUFA concentrations that are optimal for both mothers and infants.

Adult↗

Dietary polyunsaturated fatty acids and inflammatory mediator production.

Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.

Arachidonic Acid↗

Biochemical effects of a diet containing foods enriched with n-3 fatty acids.

BACKGROUND: Results of many studies indicate that consumption of n-3 fatty acids can benefit persons with cardiovascular disease and rheumatoid arthritis. However, encapsulated fish oil is unlikely to be suited to lifetime daily use and recommendations to increase fish intake have not been effective. OBJECTIVE: The objective was to examine the effectiveness of a diet that incorporates foods rich in n-3 fatty acids in elevating tissue concentrations of eicosapentaenoic acid and in suppressing the production of inflammatory mediators. DESIGN: Healthy male volunteers were provided with foods that were enriched in alpha-linolenic acid (cooking oil, margarine, salad dressing, and mayonnaise) and eicosapentaenoic and docosahexaenoic acids (sausages and savory dip) and with foods naturally rich in n-3 fatty acids, such as flaxseed meal and fish. Subjects incorporated these products into their food at home for 4 wk. Fatty acid intakes, cellular and plasma fatty acid concentrations, and monocyte-derived eicosanoid and cytokine production were measured. RESULTS: Analyses of dietary records indicated that intake of eicosapentaenoic acid plus docosahexaenoic acid averaged 1.8 g/d and intake of alpha-linolenic acid averaged 9. 0 g/d. These intakes led to an average 3-fold increase in eicosapentaenoic acid in plasma, platelet, and mononuclear cell phospholipids. Thromboxane B(2), prostaglandin E(2), and interleukin 1beta synthesis decreased by 36%, 26%, and 20% (P < 0.05), respectively. CONCLUSIONS: Foods that are strategically or naturally enriched in n-3 fatty acids can be used to achieve desired biochemical effects without the ingestion of supplements or a change in dietary habits. A wide range of n-3-enriched foods could be developed to support large-scale programs on the basis of the therapeutic and disease-preventive effects of n-3 fatty acids.

Adult↗

A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial.

OBJECTIVE: To determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA) and arachidonic acid, affect visual evoked potential (VEP) acuity of formula-fed infants, relative to breastfed infants. A secondary objective was to assess the effect of LCPUFA on Bayley's mental developmental index (MDI) and psychomotor developmental index (PDI). METHODS: Formula-fed infants were randomly allocated, in a double-blind manner, to either a placebo (no LCPUFA; n = 21), DHA supplemented (n = 23), or DHA+arachidonic acid supplemented formula (n = 24). Infants were fed their assigned formula from the first week of life until 1 year of age. A parallel reference group of breastfed infants was recruited and followed (n = 46). Infant VEP acuity was assessed at 16 and 34 weeks, and Bayley's MDI and PDI were assessed at 1 and 2 years of age. RESULTS: There were no differences among the randomized formula groups for VEP acuity at either 16 or 34 weeks of age. Breastfed infants had better VEP acuity at 34 weeks of age, but not at 16 weeks, compared with all formula-fed infants. Bayley's MDI and PDI were similar in the 3 formula-fed groups at 1 and 2 years. Breastfed infants had higher MDI scores than formula-fed infants at 2 years of age even after adjusting for environmental variables. CONCLUSIONS: LCPUFA supplementation did not influence VEP acuity development in these well-nourished, formula-fed infants.

Arachidonic Acid↗

Polyunsaturated fatty acids and infant visual development: a critical appraisal of randomized clinical trials.

At the Consensus and Controversies Conference held in Barcelona in November 1996, one of the sessions focused on an evaluation of the effects of dietary polyunsaturated fatty acids (PUFA) on infant visual development. The intervention trials in preterm and term infants were reviewed and discussed in detail. Results of these trials, particularly those in term infants, were inconsistent; much discussion occurred concerning the causes of these diverse results. We attempt to reflect, rather than report exactly, the discussion relating to these issues and address the clinical trials according to recently published guidelines for conduct and reporting of randomized clinical trials (RCT). Compared with these recent guidelines, the published papers of RCT involving PUFA and visual function are often incomplete, making it difficult to assess if we can have a high degree of confidence in the reported effects (or lack of effects). Despite this, valuable data relating to the effect of diet on the visual development of infants were obtained. Our evaluation of the trials to date suggests that the definitive answer to the degree to which dietary long-chain PUFA is likely to influence visual development may only be resolved with impeccably conducted RCT.

Fatty Acids, Unsaturated↗

Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.

Somatic mosaicism due to reversion of a pathogenic allele to wild type has been described in several autosomal recessive disorders. The best known mechanism involves intragenic mitotic recombination or gene conversion in compound heterozygous patients, whereby one allele serves to restore the wild-type sequence in the other. Here we document for the first time functional correction of a pathogenic microdeletion, microinsertion and missense mutation in homozygous Fanconi anaemia (FA) patients resulting from compensatory secondary sequence alterations in cis. The frameshift mutation 1615delG in FANCA was compensated by two additional single base-pair deletions (1637delA and 1641delT); another FANCA frameshift mutation, 3559insG, was compensated by 3580insCGCTG; and a missense mutation in FANCC(1749T-->G, Leu496Arg) was altered by 1748C-->T, creating a cysteine codon. Although in all three cases the predicted proteins were different from wild type, their cDNAs complemented the characteristic hypersensitivity of FA cells to crosslinking agents, thus establishing a functional correction to wild type.

Alleles↗

Duration of breast-feeding and Bayley's Mental Developmental Index at 1 year of age.

OBJECTIVE: To examine the association between duration of exclusive breast-feeding and developmental indices in initially breast-fed infants at 1 year of age. METHODOLOGY: A cohort of 96 healthy term infants, aged between 10 and 14 months, were recruited from public immunization clinics and child care centres in southern metropolitan Adelaide. Infants were assessed using the Bayley Scales of Infant Development (Mental and Psychomotor Developmental Indices) within 2 weeks of enrollment. Information regarding duration of breast-feeding was provided retrospectively by the mothers of the infants. Duration of exclusive breast-feeding and socio-demographic variables were used as independent variables to determine their effects on development. RESULTS: Due to a significant interaction between duration of breast-feeding and gender on mental development scores, separate regression models for boys and girls were explored. Duration of breast-feeding significantly predicted mental development scores for boys (partial r2 = 0.14, P < 0.005), but not for girls. Duration of breast-feeding did not predict psychomotor development scores. CONCLUSIONS: These findings deserve further examination in large, prospective studies.

Adult↗

The effect of breast feeding on lymphocyte subpopulations in healthy term infants at 6 months of age.

Breast milk contains many immunologically active components that influence the development of the immune system of the breast-fed infant. The purpose of this study was to investigate the difference in specific lymphocyte subsets between breast-fed and formula-fed 6-mo-old infants. Peripheral blood samples were collected from 79 breast-fed (< 120 mL formula/wk) and 69 formula-fed (breast-fed < 4 wk) infants at 6 mo. All infants had been born at term and had no known illness at the time of blood collection. Packed cells from whole blood were incubated with fluorochrome-labeled monoclonal antibodies, followed by erythrocyte lysis. Washed lymphocytes were analyzed by two-color direct immunofluorescence on a flow cytometer. The percentage of T and B lymphocytes in the peripheral blood of 6-mo-old infants was the same, regardless of feeding regimen. However, the relative frequency of natural killer (NK) cells was greater in breast-fed infants than in formula-fed infants (9.7% vs 7.1%; p < 0.001). The percentage of cells expressing CD4 was lower in breast-fed infants than in formula-fed infants (47.3% vs 50.9%; p < 0.005), and that of cells expressing CD8 was greater (18.0% vs 16.4%; p < 0.05). As a result, the CD4:CD8 ratio in breast-fed infants was lower than that in formula-fed infants (2.8 vs 3.3; p < 0.005). The absolute size of the lymphocyte subpopulations T, B, and CD8+ was the same for each of the two populations of infants. However, breast-fed infants had fewer CD4+ T cells (p < 0.05) and a greater number of NK cells (p < 0.01) than the age-matched formula-fed infants. The immunophenotypic differences between breast-fed and formula-fed infants are consistent with reported age-related changes, suggesting greater maturity in the development of the immune system of breast-fed infants.

Antigens, CD↗

Interleukin-12 in human milk.

The presence of interleukin-12 (IL-12) in 39 samples of human milk was investigated using the enzyme-linked immunosorbent assay. IL-12 (>40 pg/mL) was detected in 24 of the 39 samples collected (1408 +/- 2256 pg/mL, mean +/- SD, n = 24). A range of concentrations of IL-12 was observed in colostrum, transitional, and mature milk, with an apparent decrease in the mean concentration over time postpartum.

Adolescent↗

Cytokines (IL-1beta, IL-6, TNF-alpha, TGF-beta1, and TGF-beta2) and prostaglandin E2 in human milk during the first three months postpartum.

Postpartum changes in the concentrations of IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, and prostaglandin E2 in 257 human milk samples collected longitudinally from 49 healthy mothers during the first 12 wk of lactation were determined by ELISA or RIA. The proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were present in only a proportion of samples, and there was a wide range of concentrations detected at each time in the present study (IL-1beta, <15-400 pg/mL; IL-6, <15-1032 pg/mL; TNF-alpha, <15-2933 pg/mL). Concentrations of prostaglandin E2 increased after the first week and remained elevated for the remainder of the study (range, < 10-9966 pg/mL). The antiinflammatory cytokines TGF-beta1 (range, 43-7108 pg/mL) and TGF-beta2 (range, 208-57935 pg/mL) were present in substantial quantities in all samples, and there was little change in the mean concentration during 12 wk of lactation. The present study shows that immunomodulating agents are normally present in human milk in physiologically relevant quantities for at least the first 3 mo of the breast-fed infant's life.

Adjuvants, Immunologic↗

Developmental sensitivity of the piglet brain to docosahexanoic acid.

Human formula-fed infants have a lower concentration of docosahexanoic acid (DHA) in cerebral cortex compared with breast-fed infants. It is uncertain whether this biochemical deficit is reversible in later infancy. We used a piglet model to determine whether a critical window exists for the deposition of DHA in cerebral cortex during early postnatal development. Milk formula supplemented with DHA was fed to piglets for one of two 14-day periods commencing at either 2 or 16 d of life (early or late supplementation). Comparison of cortical DHA levels in response to supplemented formula was made with age-matched piglets receiving a control formula devoid of DHA. The level of DHA incorporated into whole brain during supplemented formula-feeding seemed to be less with increasing postnatal age. However, when cerebral cortex was examined, dietary DHA was efficiently incorporated during both early and late supplementation periods. Thus, analysis of whole brain was misleading, emphasizing the need to consider the effect of myelination when interpreting developmental changes in brain fatty acids. We conclude that the piglet cerebral cortex is responsive to dietary DHA during the postnatal phase of the brain growth spurt. The lower cortical DHA levels of human formula-fed infants may, therefore, be reversible in later infancy. Plasma phospholipid DHA levels were approximately doubled and liver phospholipid DHA levels increased 50% relative to starting values during control formula-feeding. This suggests a higher rate of DHA synthesis in the piglet in comparison with the human infant, which may be an important limitation of the piglet model.

Animal Feed↗

Dietary long-chain polyunsaturated fatty acids do not influence growth of term infants: A randomized clinical trial.

OBJECTIVE: To determine if dietary long-chain polyunsaturated fatty acids (LCPUFA) affect the growth of formula-fed infants relative to breastfed infants. METHODS: A randomized, double-blind trial of three formula-fed groups and a parallel reference group of breastfed infants was conducted. The three treatments were a placebo (no LCPUFA), docosahexaenoic acid (DHA) supplemented, and DHA plus arachidonic acid supplemented formulas fed for 12 months. Infant weight, length, head circumference, and fatty acid status were assessed at 6, 16, 34 weeks, and 1 year of age. Anthropometrics were repeated at 2 years of age. RESULTS: There were no differences between the randomized formula groups for weight, length, or head circumference even after adjustment for gender, gestational age, and the actual age at assessment. Post hoc regressions demonstrated a small negative association between DHA status at 16 weeks of age and weight at 1 and 2 years. CONCLUSIONS: Dietary LCPUFA do not influence growth of healthy term infants to a clinically significant degree.

Arachidonic Acid↗

Construction of a high-resolution physical and transcription map of chromosome 16q24.3: a region of frequent loss of heterozygosity in sporadic breast cancer.

A breast cancer tumor suppressor gene has been localized to chromosome 16q24.3 by loss of heterozygosity (LOH) studies of breast tumor DNA. To identify candidate genes for this suppressor function, we have constructed a detailed physical map extending approximately 940 kb from the telomere of the long arm of chromosome 16 that encompasses the minimum LOH interval. This contig consists of a minimum overlapping set of 35 cosmids and a single PAC clone that were aligned by restriction enzyme site mapping. Cosmids were initially identified by screening filters with markers localized to the region by physical mapping using mouse/human somatic cell hybrids, and subsequently cosmid ends were used to complete the contig. A total of seven known genes, including PRSM1, PISSLRE, and the recently cloned Fanconi anemia A (FAA) gene, and potential transcripts from exon-trapping experiments have been located to this contig. A minimum of 14 new transcripts have been identified based on homology of trapped exons with database sequences. This contig and expressed sequence map will form the basis for the identification of the breast cancer tumor suppressor gene in this region.

Breast Neoplasms↗

Iron status and dietary iron intake of 6-24-month-old children in Adelaide.

OBJECTIVE: Chronic iron deficiency in children is associated with anaemia and impaired mental and psychomotor development. The aim of this study was to assess the iron status and dietary intake of 6-24-month-old Caucasian and Asian children living in metropolitan Adelaide. METHOD: A total of 234 healthy children (82% Caucasian and 18% Asian) aged 6-24 months were studied. Dietary iron intake of children was estimated from semiquantitative diet recall questionnaire administered to their parents. Blood samples for full blood count, serum ferritin (SF), serum iron (SI) and transferrin (TF) level estimations were obtained by venesection. Based on the laboratory test results, infants were classified as iron sufficient (IS) if the haemoglobin (Hb) concentration was > 110 g L(-1), SF > or = 15 microg L(-1), TF2 3.0 g L(-1), SI > or = 8 micromol L(-1) and iron saturation (ISAT) > or = 12%; or nonanaemic iron deficiency (NAID) if the Hb concentration was > 110 g L(-1) and SF < 15 microg L(-1) or SI < 8 micromol L(-1), TF > 3.0 g L(-1), and ISAT < 12%; or as iron deficiency anaemia (IDA) if the Hb concentration was < 110 g L(-1) in association with SF < 15 microg L(-1) or with SI < 8 micromol L(-1), TF > 3.0 g L(-1) and ISAT < 12%. RESULTS: Sixty-nine per cent of Caucasian children were classified IS, 25% as NAID and 6% were IDA; while 72% of Asian children were classified IS, 14% as NAID and 14% were IDA. Multivariate analysis demonstrated that factors associated with iron deficiency (SF </5 microg L(-1)) included age, duration of breast-feeding and cows' milk intake. CONCLUSION: Iron deficiency is common in our young population. Additional strategies to prevent IDA need be developed and evaluated in Australian infants.

Anemia, Iron-Deficiency↗

The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition.

Exciting new research has shown that both preterm and term infants can actively convert the essential fatty acids linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) to long chain polyunsaturated fatty acids (LCPUFA). However, the amount of LCPUFA being produced, particularly of docosahexaenoic acid (DHA, 22:6n-3), may not be sufficient to meet the developmental requirement of the infant. Because DHA is a major component of retinal and brain tissues, a number of studies have been initiated to test the effect of dietary LCPUFA on neural outcomes in infants. These studies have largely involved a comparison of neural responses from infants fed standard infant formula (no LCPUFA) with infants receiving LCPUFA from either supplemented formula or breast milk. The results have been equivocal and may be due to the variety of LCPUFA supplements and formula fat blends used, differing testing techniques as well as variations in clinical trial conduct, but are clearer in preterm than term infants. Overall the results indicate a possible role for LCPUFA in neurodevelopment.

Breast Feeding↗

Glutathione peroxidase is not a functional marker of selenium status in the neonatal period.

BACKGROUND: The antioxidant enzyme glutathione peroxidase is a selenoprotein that, in adults with low selenium intakes, has a strong linear relationship with blood selenium and hence is used as a functional indicator of selenium status. Our aim was to evaluate glutathione peroxidase as a functional marker of selenium status in preterm infants. METHODS: Erythrocyte glutathione peroxidase activity and plasma and erythrocyte selenium were measured between days 1-5 and then weekly until discharge in 63 preterm infants with mean +/- standard error birth weight and gestation of 1572+/-60g and 30.7+/-0.3 weeks. A healthy reference group of term infants (n = 46) was assessed at day 5 and at 6 weeks. RESULTS: In preterm infants, over the first 3 months, the association of glutathione peroxidase activity with erythrocyte selenium was weak and inconsistent and nonexistent with selenium intake or plasma selenium. No correlations between any of these indicators were evident for term infants. In preterm infants, plasma and erythrocyte selenium declined over the first 6 weeks (p < 0.01), while glutathione peroxidase activity increased (p < 0.05). In term infants, plasma selenium increased (p < 0.001), but there was no change in erythrocyte selenium or glutathione peroxidase activity. For preterm infants, glutathione peroxidase activities at weeks 4 and 6 were associated with maximum inspired oxygen concentration, ventilator pressure, and days of ventilation. CONCLUSIONS: This data is consistent with animal and in vitro evidence that glutathione peroxidase may be confounded by oxygen. We conclude that erythrocyte glutathione peroxidase activity is not a reliable functional marker of preterm selenium status in the neonatal period.

Biomarkers↗