Search PubMed⌕ Search

Biomedical subjects

A J Sinclair

Publications and source records attributed to A J Sinclair.

At least 109 records · Page 6Linked to original sources

Diets rich in lean beef increase arachidonic acid and long-chain omega 3 polyunsaturated fatty acid levels in plasma phospholipids.

Diets rich in meat are claimed to contribute to the high tissue arachidonic acid (20:4 omega 6) content in people in Westernized societies, but there are very few direct data to substantiate this assertion. Because meat contains a variety of long-chain polyunsaturated fatty acids (PUFA) that are susceptible to oxidation, we initially examined the effect of cooking on the long-chain PUFA content of beef, and then determined the effect of ingestion of lean beef on the concentration of long-chain PUFA in plasma phospholipids (PL). First, we examined the effect of grilling (5-15 min) and frying (10 min) different cuts of fat-trimmed lean beef on the long-chain PUFA content. Second, we investigated the effect of including 500 g lean beef daily (raw weight) for 4 wk on the fatty acid content and composition of plasma PL in 33 healthy volunteers. This study was part of a larger trial investigating the effect of lean beef on plasma cholesterol levels. In the first two weeks, the subjects ate a very low-fat diet (10% energy) followed by an increase in the dietary fat by 10% each week for the next 2 wk. The added fat consisted of beef fat, or olive oil (as the oil or a margarine) or safflower oil (as the oil or a margarine). This quantity of beef provided 60, 230, 125, 140 and 20 mg/d, respectively, of eicosatrienoic acid (20:3 omega 6), 20:4 omega 6, eicosapentaenoic acid (20:5 omega 3), docosapentaenoic acid (22:5 omega 3) and docosahexaenoic acid (22:6 omega 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of feeding quandong (Santalum acuminatum) oil to rats on tissue lipids, hepatic cytochrome P-450 and tissue histology.

Quandong kernels are a traditional Aboriginal food item; they are rich in oil and contain large amounts of an unusual fatty acid, trans-11-octadecen-9-ynoic acid (santalbic acid), but it is not known whether this acid is absorbed and/or metabolized. The oil was fed at 12.6% of total energy content in semi-synthetic diets to groups of male Sprague-Dawley rats for 10 and 20 days. Santalbic acid was found in the lipids of plasma, adipose tissue, skeletal muscle, kidney, heart and liver but not in brain. Hepatic microsomal cytochrome P-450 activity in animals fed for 20 days was significantly higher (P < 0.05) than in controls. Histopathological examination did not reveal any lesions in the tissues of any animal fed quandong oil. The fact that santalbic acid was readily absorbed, widely distributed in tissues and was associated with an elevated level of hepatic cytochrome P-450 indicates that further studies are required to investigate whether or not there is a hazard associated with the human practice of consuming quandong kernels.

Adipose Tissue↗

n-3 fatty acids reduce in vitro thromboxane production while having little effect on in vitro prostacyclin production in the rat.

Male Sprague-Dawley rats were fed diets with 50% of the energy from fat over a 20-day period. The fats used were hydrogenated beef-fat (HBF), or HBF supplemented with ethyl arachidonate A, safflower oil (SO), or a mixture of SO and linseed oil (LO). For comparative purposes, another group of animals was fed a diet providing 50% of the energy as butter-fat. In vitro aortic prostacyclin (PGI2) and serum thromboxane (TXA2) levels (from clotting blood) were determined by radioimmunoassay of 6-keto PGF1 alpha and TXB2, respectively. The HBF diet had similar AA levels relative to the butter-fed rats but significantly reduced tissue levels of eicosapentaenoic acid (EPA) and this was associated with an increased production of serum TXB2. Supplementing the HBF diet with AA increased tissue levels of AA while maintaining low levels of n-3 fatty acids. These changes were accompanied by significant increases of both TXB2 and 6-keto-PGF1 alpha. LO supplementation to the HBF diet (with constant SO) led to elevated levels of EPA and relatively constant AA levels and this was associated with reduced production of TXB2. These results highlight the responsiveness of TXA2 to n-3 fatty acids in contrast to PGI2 which was more influenced by the level of AA in the tissue phospholipids in the rat.

6-Ketoprostaglandin F1 alpha↗

John Rivers (1945-1989): his contribution to research on polyunsaturated fatty acids in cats.

John Rivers was a remarkable person, with enormous courage and a very generous spirit. He made a significant and long-lasting impact on the science of nutrition, disaster relief and the lives of those with whom he worked. His contribution to the understanding of the essential fatty acid requirements and metabolism in the cat while working at the Nuffield Institute of Comparative Medicine is described in this paper, together with background information on the polyunsaturated fatty acid research undertaken in the Biochemistry Department at the Institute.

Animal Nutritional Physiological Phenomena↗

Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C.

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 +/- 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 +/- 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 +/- 28.3 (patients) vs 69.5 +/- 33.4 (controls) mg; questionnaire, 54.0 +/- 28.9 (patients) vs 65.0 +/- 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 +/- 19.1 mumol l-1) and dehydroascorbate (27.6 +/- 6.4 mumol l-1) levels were significantly lower in patients vs in controls (68.8 +/- 36.0 and 31.8 +/- 4.8 mumol l-1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A double-blind, placebo-controlled parallel trial of vitamin C treatment in elderly patients with hypertension.

We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Role of N-6 and N-3 fatty acids in the dietary treatment of metabolic disorders.

The impetus to examine the effects on n-3 PUFA was generated from epidemiologic studies of a traditional population largely dependent on the marine environment. These studies and clinical interventions support a recommendation to increase the consumption of n-3 fatty acids, particularly in communities that currently have a low n-3 fatty acid intake. If we are to be guided by the diet of other traditional hunter-gatherer populations, dependent on both terrestrial and marine sources of food, it is clear that we may need to reappraise the importance of long chain PUFA of the n-6 series such as arachidonic acid. Recent studies on such populations indicate that elevated arachidonic acid levels, when associated with elevated n-3 PUFA, are likely not to be harmful to health.

Arachidonic Acid↗

Strain variation in Epstein-Barr virus immediate early genes.

RNase protection analysis of mRNAs for Epstein-Barr virus (EBV) genes activated early in the induction of the productive cycle in Akata cells has confirmed that BZLF1 and BRLF1 behave as immediate early genes. These are likely to be the only virus immediate early genes since analysis of three other transcripts previously suggested to behave as immediate early genes in this system shows that they are, in fact, early genes. Western blotting of BRLF1 and BZLF1 demonstrates expression of these proteins early in induction of the productive cycle and reveals that the BZLF1 protein of Akata virus migrates more slowly on SDS gels than the BZLF1 protein of the prototypic virus strain B95-8. The nucleotide sequence of the BZLF1 gene and the immediate early promoters of Akata EBV have been determined and compared to other EBV strains. RFLP analysis of sequence variation in the BZLF1 gene of EBV strains from many different parts of the world shows a distribution of BZLF1 types which are not simply related to the established A and B EBV types.

Amino Acid Sequence↗

Differential utilization of eicosapentaenoic acid and docosahexaenoic acid in human plasma.

It has recently been shown that the omega 3 fatty acid status in humans can be predicted by the concentration of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma phospholipids [Bjerve, K.S., Brubakk, A.M., Fougner, K.J., Johnsen, H., Midjthell, K., and Vik, T. (1993) Am. J. Clin. Nutr., in press]. In countries with low intake of omega 3 fatty acids, the level of EPA in plasma phospholipids is often only about one-fifth the concentration of DHA. The purpose of this study was to investigate whether this difference in the concentration of these two fatty acids was due to a selective loss of EPA relative to DHA or to a lower dietary intake of EPA. Seven female volunteers ingested four grams of MaxEPA daily for 2 wk and in the following 4 wk they ate a diet almost completely devoid of the long-chain omega 3 fatty acids. The concentrations of the omega 3 fatty acids in the plasma cholesteryl esters, triglycerides and phospholipids and the high density lipoprotein phospholipids were examined at weekly intervals throughout the study. There was a more rapid rise in the concentration of EPA than in DHA levels in the supplementation period in all lipid fractions, but there was a disproportionate rise in DHA relative to EPA in the plasma lipids compared with the ratio in the supplement. In the depletion phase there was a rapid disappearance of EPA from all fractions, such that pre-trial levels were reached by one week post-supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect on serum lipids of addition of safflower oil or olive oil to very-low-fat diets rich in lean beef.

The cholesterol-lowering effect of very-low-fat diets rich in lean beef has previously been shown to be reversed with the addition of beef fat. The aim of this study was to determine the effect on serum lipid levels of the addition of safflower oil or olive oil to a very-low-fat diet rich in lean beef. Subjects were assigned to either the safflower oil or the olive oil group. In the first week the subjects ate their usual diet; in the second and third weeks all subjects ate a very-low-fat (9% of energy) diet rich in lean beef. In the fourth and fifth weeks the fat content of the diet was increased in a stepwise fashion to 20% and 30% of energy, respectively, by substituting safflower oil or olive oil for carbohydrate. Low-density lipoprotein cholesterol (LDL-C) concentrations decreased by 13% to 14%, and high-density lipoprotein cholesterol (HDL-C) concentrations decreased by 20% to 25% in subjects after 2 weeks of the very-low-fat, lean-beef diet. The LDL-C concentrations remained low after the addition of safflower oil or olive oil to the very-low-fat diet. These results indicate that a reduction in saturated fat, not total fat, is required to reduce serum total cholesterol and LDL-C levels. Provided that the total diet is low in saturated fat, these serum lipid responses can be achieved even when the diet is rich in fat-trimmed lean beef.

Adult↗

Arachidonic acid supplementation dose-dependently reverses the effects of a butter-enriched diet in rats.

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks which was supplemented orally with 9, 18, 36, or 72 mg/day of ethyl arachidonate for a further 2 weeks. The control group of animals were fed a 5% fat diet for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. 50% butter-feeding resulted in a significant reduction in aortic PGI2 production and collagen-induced platelet aggregation and TXA2 production. These changes were accompanied by a reduction in plasma and aortic PL arachidonic acid levels and an increase in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 5,8,11-eicosatrienoic acid (ETA) and dihomo-gamma-linolenic acid (DGLA). These changes in prostanoid production, platelet aggregation and PL fatty acid composition were dose-dependently reversed by the daily oral administration of ethyl arachidonate (9, 18, 36, or 72 mg). The threshold dose being as little as 9 mg of ethyl arachidonate/rat/day for reversal of PL fatty acid composition, collagen-induced platelet aggregation and TXA2 production, and 18 mg of ethyl arachidonate/rat/day for reversal of aortic PGI2 production. Full reversal was seen generally with 36 or 72 mg of ethyl arachidonate/rat/day. The data highlight the responsiveness of tissue eicosanoid production to small quantities (ppm) of dietary eicosanoid precursors.

Animals↗

Essential fatty acid deficiency increases interstitial IA-positive cells in rat kidney and accelerates renal allograft rejection.

Essential fatty acid deficiency has been reported to result in depletion of interstitial macrophages from rat kidneys and to permit transplantation of these kidneys across a fully allogeneic barrier without need for immunosuppression. In view of the potential for application of this phenomenon to xenografts, this study attempted to confirm the observation. Kidneys from rats fed normal or essential fatty-acid-deficient diets were transplanted to DA recipients. The donors' livers and contralateral kidneys were analyzed for their fatty acid profile in liver phospholipids, and the kidneys were examined by immunohistology for interstitial Ia(+) cells. EFAD resulted in an increase in renal interstitial Ia(+) cells detected by MRC-OX6 (anti-RT1Bpublic) from 13.5 +/- 2.9 (control diet fed rats) to 22.8 +/- 3.6 in rats on a stringent EFAD diet. Graft survival of kidneys from these EFAD rats was significantly shorter than that of kidneys from control diet fed rats. In direct contrast to the original report, this study found that EFAD caused a marked increase in renal interstitial Ia(+) cells and a reduction in allograft survival of EFAD donor kidneys.

Animals↗

An investigation of a nosocomial outbreak of Clostridium difficile by pyrolysis mass spectrometry.

Isolates from a presumptive nosocomial outbreak of Clostridium difficile infection at a large teaching hospital were typed by pyrolysis mass spectrometry (PMS) and antibiograms. One isolate, from the putative index case, was dissimilar from the outbreak strain, but 24 isolates from 16 patients were indistinguishable by both methods. The outbreak centred on two wards for the acute care of the elderly, with a few cases elsewhere. Transfer of patients appeared to be the route of transmission between wards. There was a significant fall in the incidence of cases following intervention by the Infection Control Unit. This included ward inspection, advice on antibiotic usage and advice on prevention of faecal-oral transfer, particularly by proper handwashing. Subsequent monitoring of C. difficile infection showed a background of sporadic, dissimilar isolates with occasional apparent cross-infection incidents limited to a few patients. In suspected outbreaks, patterns of antibiotic susceptibility may be useful in initial screening, before referral for more sophisticated typing. There was excellent correlation between PMS results, antibiograms and epidemiological information.

Aged↗